IL104961A - הכנתן של חומצות 4 - דמתוקסידאונומיצינון - 4 - קרבוסילות ואסטרים שלהן - Google Patents

הכנתן של חומצות 4 - דמתוקסידאונומיצינון - 4 - קרבוסילות ואסטרים שלהן

Info

Publication number: IL104961A
Authority: IL; Israel
Prior art keywords: formula; group; process according; compound; vii
Prior art date: 1989-03-02

Application number

IL10496190A

Other languages

English (en)

Original Assignee

Erba Carlo Spa

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.)

1989-03-02

Filing date

1990-02-27

Publication date

1994-06-24

1989-03-02 Priority claimed from GB898904794A external-priority patent/GB8904794D0/en

1990-02-27 Application filed by Erba Carlo Spa filed Critical Erba Carlo Spa

1994-06-24 Publication of IL104961A publication Critical patent/IL104961A/he

Links

238000002360 preparation method Methods 0.000 title claims description 6
150000002148 esters Chemical class 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims description 18
238000000034 method Methods 0.000 claims description 16
239000002585 base Substances 0.000 claims description 11
125000000217 alkyl group Chemical group 0.000 claims description 10
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 9
239000003054 catalyst Substances 0.000 claims description 8
239000002904 solvent Substances 0.000 claims description 7
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 6
125000005843 halogen group Chemical group 0.000 claims description 6
UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 claims description 5
125000003545 alkoxy group Chemical group 0.000 claims description 5
125000004432 carbon atom Chemical group C* 0.000 claims description 5
229910002091 carbon monoxide Inorganic materials 0.000 claims description 5
239000000741 silica gel Substances 0.000 claims description 5
229910002027 silica gel Inorganic materials 0.000 claims description 5
150000003624 transition metals Chemical group 0.000 claims description 5
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical group [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 4
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical group [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 4
238000005903 acid hydrolysis reaction Methods 0.000 claims description 4
125000003118 aryl group Chemical group 0.000 claims description 4
-1 alkaline earth metal carbonate Chemical class 0.000 claims description 3
150000001450 anions Chemical class 0.000 claims description 3
OAIVIYSBZFEOIU-UHFFFAOYSA-N chloroform;propan-2-one Chemical compound CC(C)=O.ClC(Cl)Cl OAIVIYSBZFEOIU-UHFFFAOYSA-N 0.000 claims description 3
229910052736 halogen Inorganic materials 0.000 claims description 3
230000007935 neutral effect Effects 0.000 claims description 3
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
239000012038 nucleophile Substances 0.000 claims description 3
125000006239 protecting group Chemical group 0.000 claims description 3
239000007858 starting material Substances 0.000 claims description 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
239000003513 alkali Substances 0.000 claims description 2
229910052799 carbon Inorganic materials 0.000 claims description 2
238000004587 chromatography analysis Methods 0.000 claims description 2
239000012043 crude product Substances 0.000 claims description 2
150000004985 diamines Chemical class 0.000 claims description 2
239000003480 eluent Substances 0.000 claims description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
150000007529 inorganic bases Chemical class 0.000 claims description 2
229910052759 nickel Chemical group 0.000 claims description 2
229910052763 palladium Inorganic materials 0.000 claims description 2
OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 claims description 2
229910000073 phosphorus hydride Inorganic materials 0.000 claims description 2
125000005270 trialkylamine group Chemical group 0.000 claims description 2
229910052784 alkaline earth metal Inorganic materials 0.000 claims 2
230000006315 carbonylation Effects 0.000 claims 1
238000005810 carbonylation reaction Methods 0.000 claims 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims 1
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 10
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
239000011541 reaction mixture Substances 0.000 description 8
YOFDHOWPGULAQF-UHFFFAOYSA-N Daunomycin-Aglycone Natural products C1C(O)(C(C)=O)CC(O)C2=C1C(O)=C1C(=O)C(C=CC=C3OC)=C3C(=O)C1=C2O YOFDHOWPGULAQF-UHFFFAOYSA-N 0.000 description 7
238000004128 high performance liquid chromatography Methods 0.000 description 7
YOFDHOWPGULAQF-MQJDWESPSA-N (7s,9s)-9-acetyl-6,7,9,11-tetrahydroxy-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione Chemical compound C1[C@@](O)(C(C)=O)C[C@H](O)C2=C1C(O)=C1C(=O)C(C=CC=C3OC)=C3C(=O)C1=C2O YOFDHOWPGULAQF-MQJDWESPSA-N 0.000 description 6
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
101150041968 CDC13 gene Proteins 0.000 description 6
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
238000006243 chemical reaction Methods 0.000 description 6
239000012074 organic phase Substances 0.000 description 5
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
229910052938 sodium sulfate Inorganic materials 0.000 description 4
235000011152 sodium sulphate Nutrition 0.000 description 4
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
238000005160 1H NMR spectroscopy Methods 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
238000011065 in-situ storage Methods 0.000 description 3
239000000203 mixture Substances 0.000 description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 2
OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 2
MSHFRERJPWKJFX-UHFFFAOYSA-N 4-Methoxybenzyl alcohol Chemical compound COC1=CC=C(CO)C=C1 MSHFRERJPWKJFX-UHFFFAOYSA-N 0.000 description 2
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
238000005481 NMR spectroscopy Methods 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
238000010521 absorption reaction Methods 0.000 description 2
229940045799 anthracyclines and related substance Drugs 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
150000002367 halogens Chemical group 0.000 description 2
239000000543 intermediate Substances 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
ODKLEQPZOCJQMT-UHFFFAOYSA-N n,n-diethylpyridin-4-amine Chemical compound CCN(CC)C1=CC=NC=C1 ODKLEQPZOCJQMT-UHFFFAOYSA-N 0.000 description 2
239000002243 precursor Substances 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
239000007787 solid Substances 0.000 description 2
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 1
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
BFXHJFKKRGVUMU-UHFFFAOYSA-N 4-fluorobenzenesulfonyl chloride Chemical compound FC1=CC=C(S(Cl)(=O)=O)C=C1 BFXHJFKKRGVUMU-UHFFFAOYSA-N 0.000 description 1
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
101100028482 Caenorhabditis elegans pal-1 gene Proteins 0.000 description 1
BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
101000837626 Homo sapiens Thyroid hormone receptor alpha Proteins 0.000 description 1
UEZVMMHDMIWARA-UHFFFAOYSA-N Metaphosphoric acid Chemical compound OP(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-N 0.000 description 1
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
102100028702 Thyroid hormone receptor alpha Human genes 0.000 description 1
239000002253 acid Substances 0.000 description 1
230000000259 anti-tumor effect Effects 0.000 description 1
125000005228 aryl sulfonate group Chemical group 0.000 description 1
238000010533 azeotropic distillation Methods 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
150000004649 carbonic acid derivatives Chemical class 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
125000006364 carbonyl oxy methylene group Chemical group [H]C([H])([*:2])OC([*:1])=O 0.000 description 1
238000006555 catalytic reaction Methods 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
230000017858 demethylation Effects 0.000 description 1
238000010520 demethylation reaction Methods 0.000 description 1
238000001035 drying Methods 0.000 description 1
125000004185 ester group Chemical group 0.000 description 1
238000001914 filtration Methods 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
229930182470 glycoside Natural products 0.000 description 1
150000002338 glycosides Chemical class 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
238000007327 hydrogenolysis reaction Methods 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
150000004679 hydroxides Chemical class 0.000 description 1
JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 description 1
125000000468 ketone group Chemical group 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
125000000896 monocarboxylic acid group Chemical group 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
239000012071 phase Substances 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
150000003003 phosphines Chemical class 0.000 description 1
125000006684 polyhaloalkyl group Polymers 0.000 description 1
239000000047 product Substances 0.000 description 1
238000010992 reflux Methods 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
REFMEZARFCPESH-UHFFFAOYSA-M sodium;heptane-1-sulfonate Chemical compound [Na+].CCCCCCCS([O-])(=O)=O REFMEZARFCPESH-UHFFFAOYSA-M 0.000 description 1
239000000725 suspension Substances 0.000 description 1
238000006257 total synthesis reaction Methods 0.000 description 1
229910052723 transition metal Inorganic materials 0.000 description 1
125000005208 trialkylammonium group Chemical group 0.000 description 1
WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 1
COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

IL10496190A 1989-03-02 1990-02-27 הכנתן של חומצות 4 - דמתוקסידאונומיצינון - 4 - קרבוסילות ואסטרים שלהן IL104961A (he)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GB898904794A GB8904794D0 (en)	1989-03-02	1989-03-02	Process for preparing anthracyclinones
IL9355990A IL93559A (he)	1989-03-02	1990-02-27	הכנת 4-דמתוקסידונומיצינון

Publications (1)

Publication Number	Publication Date
IL104961A true IL104961A (he)	1994-06-24

Family

ID=26295039

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
IL10496190A IL104961A (he)	1989-03-02	1990-02-27	הכנתן של חומצות 4 - דמתוקסידאונומיצינון - 4 - קרבוסילות ואסטרים שלהן
IL104961A IL104961A0 (en)	1989-03-02	1993-03-05	Preparation of anthracyclinones

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
IL104961A IL104961A0 (en)	1989-03-02	1993-03-05	Preparation of anthracyclinones

Country Status (1)

Country	Link
IL (2)	IL104961A (he)

1990
- 1990-02-27 IL IL10496190A patent/IL104961A/he not_active IP Right Cessation
1993
- 1993-03-05 IL IL104961A patent/IL104961A0/xx unknown

Also Published As

Publication number	Publication date
IL104961A0 (en)	1993-07-08

Legal Events

Date	Code	Title
1996-05-14	KB	Patent renewed
1997-03-18	HC	Change of name of proprietor(s)
2000-08-13	KB	Patent renewed
2003-12-10	RH1	Patent not in force
2004-03-28	KB	Patent renewed
2005-07-25	MM9K	Patent not in force due to non-payment of renewal fees

Publication	Publication Date	Title
EP0434960B1 (en)	1996-09-18	Chiral 1,5-diiodo-2-methoxy or benzyloxy intermediates
US5103029A (en)	1992-04-07	Process for preparing 4-demethoxydaunomycinone
AU636134B2 (en)	1993-04-22	Process for preparing anthracyclinones
EP0354995B1 (en)	1992-01-02	4-substituted anthracyclinones and anthracycline glycosides and their preparation
IL104961A (he)	1994-06-24	הכנתן של חומצות 4 - דמתוקסידאונומיצינון - 4 - קרבוסילות ואסטרים שלהן
SI9010399A (sl)	1998-02-28	Postopek za pripravo antraciklinonov
IL104975A (he)	1994-06-24	חומצות 4-דמתוקסידוקסורוביצין- ודאונומיצין -4-קרבוקסילית אסטרים שלהם, הכנתם ותכשירי רוקחות המכילים אותם
SI8910718A (sl)	1997-02-28	Postopek za pripravo 4-demetoksidavnomicinona