IL117225A - Preparation of T4D from 5 methyluridine, and several intermediates for this - Google Patents

Preparation of T4D from 5 methyluridine, and several intermediates for this

Info

Publication number: IL117225A
Authority: IL; Israel
Prior art keywords: mixture; compound; afford; bromo; treating
Prior art date: 1995-03-10

Application number

IL11722596A

Other languages

English (en)

Hebrew (he)

Other versions

IL117225A0 (en

Original Assignee

Bristol Myers Squibb Co

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1995-03-10

Filing date

1996-02-22

Publication date

2001-04-30

1996-02-22 Application filed by Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co

1996-06-18 Publication of IL117225A0 publication Critical patent/IL117225A0/xx

2001-04-30 Publication of IL117225A publication Critical patent/IL117225A/en

Links

DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 title description 17
DWRXFEITVBNRMK-JXOAFFINSA-N ribothymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 DWRXFEITVBNRMK-JXOAFFINSA-N 0.000 title description 14
238000002360 preparation method Methods 0.000 title description 5
239000000543 intermediate Substances 0.000 title description 4
239000000203 mixture Substances 0.000 claims abstract description 47
150000001875 compounds Chemical class 0.000 claims abstract description 39
XNKLLVCARDGLGL-JGVFFNPUSA-N Stavudine Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1C=C[C@@H](CO)O1 XNKLLVCARDGLGL-JGVFFNPUSA-N 0.000 claims abstract description 36
238000000034 method Methods 0.000 claims abstract description 34
125000001246 bromo group Chemical group Br* 0.000 claims abstract description 17
229910052751 metal Inorganic materials 0.000 claims abstract description 17
239000002184 metal Substances 0.000 claims abstract description 17
150000001266 acyl halides Chemical class 0.000 claims abstract description 9
229910052784 alkaline earth metal Inorganic materials 0.000 claims abstract description 9
150000002118 epoxides Chemical class 0.000 claims abstract description 9
229910000039 hydrogen halide Inorganic materials 0.000 claims abstract description 9
239000012433 hydrogen halide Substances 0.000 claims abstract description 9
150000008044 alkali metal hydroxides Chemical class 0.000 claims abstract description 8
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims abstract description 6
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims abstract description 6
125000003118 aryl group Chemical group 0.000 claims abstract description 6
229910052749 magnesium Inorganic materials 0.000 claims abstract description 6
239000011777 magnesium Substances 0.000 claims abstract description 6
229910052708 sodium Inorganic materials 0.000 claims abstract description 6
239000011734 sodium Substances 0.000 claims abstract description 6
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims abstract description 5
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims abstract description 5
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims abstract description 5
239000003513 alkali Substances 0.000 claims abstract description 5
150000001342 alkaline earth metals Chemical class 0.000 claims abstract description 5
229910052791 calcium Inorganic materials 0.000 claims abstract description 5
239000011575 calcium Substances 0.000 claims abstract description 5
229910052744 lithium Inorganic materials 0.000 claims abstract description 5
229910052700 potassium Inorganic materials 0.000 claims abstract description 5
239000011591 potassium Substances 0.000 claims abstract description 5
125000002346 iodo group Chemical group I* 0.000 claims abstract 10
125000001309 chloro group Chemical group Cl* 0.000 claims abstract 9
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract 3
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 21
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 14
125000000217 alkyl group Chemical group 0.000 claims description 14
229910052725 zinc Inorganic materials 0.000 claims description 13
239000011701 zinc Substances 0.000 claims description 13
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 12
238000006243 chemical reaction Methods 0.000 claims description 11
FXXACINHVKSMDR-UHFFFAOYSA-N acetyl bromide Chemical compound CC(Br)=O FXXACINHVKSMDR-UHFFFAOYSA-N 0.000 claims description 8
229910000042 hydrogen bromide Inorganic materials 0.000 claims description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 claims description 5
239000007983 Tris buffer Substances 0.000 claims description 4
WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 claims description 4
235000010234 sodium benzoate Nutrition 0.000 claims description 4
239000004299 sodium benzoate Substances 0.000 claims description 4
150000003973 alkyl amines Chemical class 0.000 claims 4
239000003638 chemical reducing agent Substances 0.000 claims 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
229910052739 hydrogen Inorganic materials 0.000 claims 1
239000001257 hydrogen Substances 0.000 claims 1
229910000000 metal hydroxide Inorganic materials 0.000 claims 1
150000004692 metal hydroxides Chemical class 0.000 claims 1
ASGMFNBUXDJWJJ-JLCFBVMHSA-N (1R,3R)-3-[[3-bromo-1-[4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl]pyrazolo[3,4-d]pyrimidin-6-yl]amino]-N,1-dimethylcyclopentane-1-carboxamide Chemical compound BrC1=NN(C2=NC(=NC=C21)N[C@H]1C[C@@](CC1)(C(=O)NC)C)C1=CC=C(C=C1)C=1SC(=NN=1)C ASGMFNBUXDJWJJ-JLCFBVMHSA-N 0.000 abstract 1
229940127007 Compound 39 Drugs 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 18
RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 14
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 13
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 10
229940113082 thymine Drugs 0.000 description 10
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 9
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 7
239000002002 slurry Substances 0.000 description 7
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
238000005481 NMR spectroscopy Methods 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
239000000047 product Substances 0.000 description 6
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
238000005160 1H NMR spectroscopy Methods 0.000 description 5
239000011541 reaction mixture Substances 0.000 description 5
239000000243 solution Substances 0.000 description 5
239000002904 solvent Substances 0.000 description 5
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
BKZQWZPYZIYYAQ-UONOGXRCSA-N [(2s,5r)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)-2,5-dihydrofuran-2-yl]methyl benzoate Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1C=C[C@@H](COC(=O)C=2C=CC=CC=2)O1 BKZQWZPYZIYYAQ-UONOGXRCSA-N 0.000 description 4
238000001914 filtration Methods 0.000 description 4
HJQJVBNQTDABCR-VLCSVPMDSA-N 1-[(2r,5s)-5-[hydroxy(methylsulfonyl)methyl]-2,5-dihydrofuran-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1C=C[C@@H](C(O)S(C)(=O)=O)O1 HJQJVBNQTDABCR-VLCSVPMDSA-N 0.000 description 3
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
239000003443 antiviral agent Substances 0.000 description 3
239000006227 byproduct Substances 0.000 description 3
125000004432 carbon atom Chemical group C* 0.000 description 3
238000001816 cooling Methods 0.000 description 3
125000005843 halogen group Chemical group 0.000 description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
238000006894 reductive elimination reaction Methods 0.000 description 3
238000003756 stirring Methods 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
BRSAJIPNDBWROP-SBAJUTMZSA-N 1-[(1r,2r,4s,5s)-4-[hydroxy(methylsulfonyl)methyl]-3,6-dioxabicyclo[3.1.0]hexan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1[C@@H]2O[C@@H]2[C@@H](C(O)S(C)(=O)=O)O1 BRSAJIPNDBWROP-SBAJUTMZSA-N 0.000 description 2
XLYOFNOQVPJJNP-ZSJDYOACSA-N Heavy water Chemical compound [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 2
239000012359 Methanesulfonyl chloride Substances 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
125000002252 acyl group Chemical group 0.000 description 2
239000002585 base Substances 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
LTJLLEBCZILXAO-UHFFFAOYSA-N bromo acetate Chemical class CC(=O)OBr LTJLLEBCZILXAO-UHFFFAOYSA-N 0.000 description 2
238000010511 deprotection reaction Methods 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
238000002955 isolation Methods 0.000 description 2
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
125000000371 nucleobase group Chemical group 0.000 description 2
150000007530 organic bases Chemical class 0.000 description 2
230000000737 periodic effect Effects 0.000 description 2
239000002798 polar solvent Substances 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
238000010992 reflux Methods 0.000 description 2
239000011347 resin Substances 0.000 description 2
229920005989 resin Polymers 0.000 description 2
230000003595 spectral effect Effects 0.000 description 2
BMFGLXWWIGPMOM-IHPAWCCZSA-N 1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-[hydroxy(methylsulfonyl)methyl]-3,4-bis(methylsulfonyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1[C@](S(C)(=O)=O)(O)[C@@](O)(S(C)(=O)=O)[C@@H](C(O)S(C)(=O)=O)O1 BMFGLXWWIGPMOM-IHPAWCCZSA-N 0.000 description 1
SSJHJHMZBKEKQQ-IKCIUXDWSA-N 1-[(2r,5s)-5-(1-hydroxy-2-oxo-2-phenylethyl)-2,5-dihydrofuran-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1C=C[C@@H](C(O)C(=O)C=2C=CC=CC=2)O1 SSJHJHMZBKEKQQ-IKCIUXDWSA-N 0.000 description 1
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical class CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 1
JVKRKMWZYMKVTQ-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]pyrazol-1-yl]-N-(2-oxo-3H-1,3-benzoxazol-6-yl)acetamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C=NN(C=1)CC(=O)NC1=CC2=C(NC(O2)=O)C=C1 JVKRKMWZYMKVTQ-UHFFFAOYSA-N 0.000 description 1
BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical class CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
125000005917 3-methylpentyl group Chemical group 0.000 description 1
DEXFNLNNUZKHNO-UHFFFAOYSA-N 6-[3-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperidin-1-yl]-3-oxopropyl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1CCN(CC1)C(CCC1=CC2=C(NC(O2)=O)C=C1)=O DEXFNLNNUZKHNO-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
208000030507 AIDS Diseases 0.000 description 1
229930024421 Adenine Natural products 0.000 description 1
GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
OIRDTQYFTABQOQ-KQYNXXCUSA-N Adenosine Natural products C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
239000002126 C01EB10 - Adenosine Substances 0.000 description 1
KDISRUAHXPKXFK-YJRXYDGGSA-N CS(=O)(=O)[C@@]1([C@]([C@@](O[C@@H]1CO)(N1C(=O)NC(=O)C(=C1)C)S(=O)(=O)C)(O)S(=O)(=O)C)O Chemical compound CS(=O)(=O)[C@@]1([C@]([C@@](O[C@@H]1CO)(N1C(=O)NC(=O)C(=C1)C)S(=O)(=O)C)(O)S(=O)(=O)C)O KDISRUAHXPKXFK-YJRXYDGGSA-N 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
-1 Methanesulfonyl DMF Chemical compound 0.000 description 1
AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 1
208000034809 Product contamination Diseases 0.000 description 1
GBELRGLGJVBJQR-WUQSDXJHSA-N S(=O)(=O)(C)C([C@@H]1[C@@H]2[C@H]([C@@H](O1)N1C(=O)NC(=O)C=C1)O2)O Chemical compound S(=O)(=O)(C)C([C@@H]1[C@@H]2[C@H]([C@@H](O1)N1C(=O)NC(=O)C=C1)O2)O GBELRGLGJVBJQR-WUQSDXJHSA-N 0.000 description 1
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
229910007565 Zn—Cu Inorganic materials 0.000 description 1
239000002253 acid Substances 0.000 description 1
125000004423 acyloxy group Chemical group 0.000 description 1
229960000643 adenine Drugs 0.000 description 1
229960005305 adenosine Drugs 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
238000013459 approach Methods 0.000 description 1
150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
239000012267 brine Substances 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
239000000460 chlorine Substances 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
238000013375 chromatographic separation Methods 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
230000002860 competitive effect Effects 0.000 description 1
229940125782 compound 2 Drugs 0.000 description 1
239000000356 contaminant Substances 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
TVZPLCNGKSPOJA-UHFFFAOYSA-N copper zinc Chemical compound [Cu].[Zn] TVZPLCNGKSPOJA-UHFFFAOYSA-N 0.000 description 1
238000009510 drug design Methods 0.000 description 1
230000000694 effects Effects 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
239000012065 filter cake Substances 0.000 description 1
238000009472 formulation Methods 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
125000001475 halogen functional group Chemical group 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
229910000041 hydrogen chloride Inorganic materials 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
229910000043 hydrogen iodide Inorganic materials 0.000 description 1
BTJRKNUKPQBLAL-UHFFFAOYSA-N hydron;4-methylmorpholine;chloride Chemical compound Cl.CN1CCOCC1 BTJRKNUKPQBLAL-UHFFFAOYSA-N 0.000 description 1
CUILPNURFADTPE-UHFFFAOYSA-N hypobromous acid Chemical class BrO CUILPNURFADTPE-UHFFFAOYSA-N 0.000 description 1
239000005457 ice water Substances 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
239000011630 iodine Substances 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
NBTOZLQBSIZIKS-UHFFFAOYSA-N methoxide Chemical compound [O-]C NBTOZLQBSIZIKS-UHFFFAOYSA-N 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
238000012552 review Methods 0.000 description 1
239000002342 ribonucleoside Substances 0.000 description 1
230000007017 scission Effects 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
239000007787 solid Substances 0.000 description 1
239000012265 solid product Substances 0.000 description 1
239000012453 solvate Substances 0.000 description 1
239000007858 starting material Substances 0.000 description 1
229960001203 stavudine Drugs 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
229940104230 thymidine Drugs 0.000 description 1
238000005292 vacuum distillation Methods 0.000 description 1
229940087450 zerit Drugs 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Molecular Biology (AREA)
Virology (AREA)
Genetics & Genomics (AREA)
Biotechnology (AREA)
Biochemistry (AREA)
Engineering & Computer Science (AREA)
General Chemical & Material Sciences (AREA)
Oncology (AREA)
Pharmacology & Pharmacy (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Animal Behavior & Ethology (AREA)
Communicable Diseases (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Medicinal Chemistry (AREA)
Chemical Kinetics & Catalysis (AREA)
AIDS & HIV (AREA)
Tropical Medicine & Parasitology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Saccharide Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)

IL11722596A 1995-03-10 1996-02-22 Preparation of T4D from 5 methyluridine, and several intermediates for this IL117225A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US08/402,283 US5608049A (en)	1995-03-10	1995-03-10	Preparation of d4T from 5-methyluridine

Publications (2)

Publication Number	Publication Date
IL117225A0 IL117225A0 (en)	1996-06-18
IL117225A true IL117225A (en)	2001-04-30

Family

ID=23591286

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL11722596A IL117225A (en)	1995-03-10	1996-02-22	Preparation of T4D from 5 methyluridine, and several intermediates for this

Country Status (17)

Country	Link
US (1)	US5608049A (de)
EP (1)	EP0735044B1 (de)
JP (1)	JP3914279B2 (de)
KR (1)	KR100393913B1 (de)
CN (2)	CN1059213C (de)
AT (1)	ATE181556T1 (de)
AU (1)	AU694320B2 (de)
CA (1)	CA2170968A1 (de)
CY (1)	CY2155B1 (de)
DE (1)	DE69602983T2 (de)
DK (1)	DK0735044T3 (de)
ES (1)	ES2135168T3 (de)
GR (1)	GR3031243T3 (de)
HU (1)	HU220700B1 (de)
IL (1)	IL117225A (de)
SG (1)	SG38948A1 (de)
TW (1)	TW527359B (de)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5608048A (en) *	1995-06-05	1997-03-04	Bristol-Myers Squibb Company	d4 T polymorphic Form 1 process
WO2002020538A2 (en) *	2000-09-06	2002-03-14	Bristol-Myers Squibb Company	Stavudine polymorphic form 1 process
JP2007522094A (ja) *	2003-09-22	2007-08-09	アシドフィルエルエルシー	小分子組成物、及びその組成物を使用して薬物効率を高めるための方法
US7160537B2 (en) *	2003-12-15	2007-01-09	Siemens Medical Solutions Usa, Inc.	Method for preparing radiolabeled thymidine having low chromophoric byproducts
US20050131224A1 (en) *	2003-12-15	2005-06-16	Cti Pet Systems, Inc.	Method for preparing radiolabeled thymidine

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3817982A (en) *	1971-12-29	1974-06-18	Syntex Inc	2{40 ,3{40 -unsaturated nucleosides and method of making
US4904770A (en) *	1988-03-24	1990-02-27	Bristol-Myers Company	Production of 2',3'-dideoxy-2',3'-didehydronucleosides
JP3128080B2 (ja) *	1991-10-02	2001-01-29	日本製紙株式会社	核酸化合物の新規な製造方法
US5672698A (en) *	1993-11-15	1997-09-30	Bristol-Myers Squibb Co.	Preparation of 2',3'-didehydro-3'-deoxythymidine from 5-methyluridine
US5539099A (en) *	1993-11-15	1996-07-23	Bristol-Myers Squibb Company	Process for large-scale preparation of 2',3'-didehydro-2',3'-dideoxynucleosides

1995
- 1995-03-10 US US08/402,283 patent/US5608049A/en not_active Expired - Lifetime
1996
- 1996-02-17 TW TW085102080A patent/TW527359B/zh not_active IP Right Cessation
- 1996-02-22 IL IL11722596A patent/IL117225A/en not_active IP Right Cessation
- 1996-03-04 CA CA002170968A patent/CA2170968A1/en not_active Abandoned
- 1996-03-05 JP JP04700596A patent/JP3914279B2/ja not_active Expired - Fee Related
- 1996-03-05 KR KR1019960005683A patent/KR100393913B1/ko not_active Expired - Fee Related
- 1996-03-08 AT AT96301606T patent/ATE181556T1/de not_active IP Right Cessation
- 1996-03-08 EP EP96301606A patent/EP0735044B1/de not_active Expired - Lifetime
- 1996-03-08 CN CN96105786A patent/CN1059213C/zh not_active Expired - Fee Related
- 1996-03-08 AU AU47982/96A patent/AU694320B2/en not_active Ceased
- 1996-03-08 DE DE69602983T patent/DE69602983T2/de not_active Expired - Fee Related
- 1996-03-08 ES ES96301606T patent/ES2135168T3/es not_active Expired - Lifetime
- 1996-03-08 HU HU9600607A patent/HU220700B1/hu not_active IP Right Cessation
- 1996-03-08 DK DK96301606T patent/DK0735044T3/da active
- 1996-03-08 CN CNB001009850A patent/CN1195770C/zh not_active Expired - Fee Related
- 1996-03-09 SG SG1996006654A patent/SG38948A1/en unknown
1999
- 1999-08-03 CY CY9900022A patent/CY2155B1/xx unknown
- 1999-09-16 GR GR990402335T patent/GR3031243T3/el unknown

Also Published As

Publication number	Publication date
KR960034212A (ko)	1996-10-22
CN1270172A (zh)	2000-10-18
JP3914279B2 (ja)	2007-05-16
CN1147519A (zh)	1997-04-16
AU694320B2 (en)	1998-07-16
HK1002979A1 (en)	1998-09-30
KR100393913B1 (ko)	2003-12-18
DE69602983T2 (de)	2000-03-09
IL117225A0 (en)	1996-06-18
CA2170968A1 (en)	1996-09-11
CY2155B1 (en)	2002-08-23
AU4798296A (en)	1996-09-19
CN1059213C (zh)	2000-12-06
DK0735044T3 (da)	2000-01-10
CN1195770C (zh)	2005-04-06
US5608049A (en)	1997-03-04
DE69602983D1 (de)	1999-07-29
EP0735044A1 (de)	1996-10-02
SG38948A1 (en)	1997-04-17
ATE181556T1 (de)	1999-07-15
EP0735044B1 (de)	1999-06-23
HU220700B1 (hu)	2002-04-29
GR3031243T3 (en)	1999-12-31
ES2135168T3 (es)	1999-10-16
JPH08269051A (ja)	1996-10-15
TW527359B (en)	2003-04-11
HUP9600607A1 (en)	1996-12-30

Legal Events

Date	Code	Title
2001-10-31	FF	Patent granted
2001-11-25	KB	Patent renewed
2006-04-10	KB	Patent renewed
2010-12-30	MM9K	Patent not in force due to non-payment of renewal fees

Publication	Publication Date	Title
EP0521923B1 (de)	1995-03-08	Verfahren zur herstellung von nucleosiden und ihre analogen
JP3653292B2 (ja)	2005-05-25	５−メチルウリジンを用いる２’，３’−ジデヒドロ−３’−デオキシチミジン（ｄ４Ｔ）の大量製造法
JP3677790B2 (ja)	2005-08-03	ヌクレオシド誘導体とその製造方法
EP0735044B1 (de)	1999-06-23	Darstellung von D4T aus 5-Methyluridin
AU672533B2 (en)	1996-10-03	Process for preparing AZT and derivatives thereof
JPH06135988A (ja)	1994-05-17	ヌクレオシド誘導体
JPH0217199A (ja)	1990-01-22	２’−デオキシ−β−アデノシンの製造方法
KR100699099B1 (ko)	2007-03-22	1-α-할로-2,2-다이플루오로-2-데옥시-Ｄ-라이보퓨라노스유도체 및 이의 제조방법
HK1002979B (en)	2000-04-28	Preparation of d4t from 5-methyluridine
KR20060125830A (ko)	2006-12-06	2―치환 아데노신의 개선된 합성
JP2666160B2 (ja)	1997-10-22	５−ｏ−ピリミジル−２，３−ジデオキシ−１−チオフラノシド誘導体，その製造方法及び用途
US5536824A (en)	1996-07-16	Organosulfonyl salts of 2,3'-O-cyclocytidine
CN100455591C (zh)	2009-01-28	改进的2-取代腺苷的合成
KR101259648B1 (ko)	2013-05-09	2′,2′-디플루오로뉴클레오시드 및 중간체의 새로운 제조방법
JPH10504548A (ja)	1998-05-06	２−ｄ−ペントフラノシド誘導体、その製造方法及びその使用
JPH06135989A (ja)	1994-05-17	ヌクレオシド誘導体
HK1095834B (en)	2009-09-04	Improved synthesis of 2-substituted adenosines
JPH0529039B2 (de)	1993-04-28