DD201896A5 - Verfahren zur herstellung neuer in 5-position substituierter 2,4-diamino-pyrimidine - Google Patents

Info

Publication number

DD201896A5

DD201896A5 DD81234745A DD23474581A DD201896A5 DD 201896 A5 DD201896 A5 DD 201896A5 DD 81234745 A DD81234745 A DD 81234745A DD 23474581 A DD23474581 A DD 23474581A DD 201896 A5 DD201896 A5 DD 201896A5

Authority

DD

German Democratic Republic

Prior art keywords

diamino

pyrimidine

radical

amino

formula

Prior art date

1980-11-11

Links

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• Global Dossier
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• 238000000034 method Methods 0.000 title claims abstract description 77
• 238000002360 preparation method Methods 0.000 title claims abstract description 27
• 230000008569 process Effects 0.000 title claims abstract description 18
• 229940058936 antimalarials diaminopyrimidines Drugs 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 202
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 50
• 150000003839 salts Chemical class 0.000 claims abstract description 35
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 27
• 125000002252 acyl group Chemical group 0.000 claims abstract description 19
• 150000001204 N-oxides Chemical class 0.000 claims abstract description 12
• 125000001424 substituent group Chemical group 0.000 claims abstract description 11
• 125000005842 heteroatom Chemical group 0.000 claims abstract description 7
• 125000004429 atom Chemical group 0.000 claims abstract description 6
• -1 cyano, hydroxy, mercapto Chemical class 0.000 claims description 156
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 81
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 65
• 229910052739 hydrogen Inorganic materials 0.000 claims description 64
• 239000001257 hydrogen Substances 0.000 claims description 62
• 229910052736 halogen Inorganic materials 0.000 claims description 49
• 150000003254 radicals Chemical class 0.000 claims description 49
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 40
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 38
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 36
• 238000006243 chemical reaction Methods 0.000 claims description 36
• 125000005843 halogen group Chemical group 0.000 claims description 31
• 150000002367 halogens Chemical class 0.000 claims description 27
• 229910052757 nitrogen Inorganic materials 0.000 claims description 26
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 24
• ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 20
• MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical class [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 18
• 229910052799 carbon Inorganic materials 0.000 claims description 17
• NWFFAMNYFYKTDZ-UHFFFAOYSA-N 5-[(7,8-dimethoxy-2h-chromen-5-yl)methyl]pyrimidine-2,4-diamine Chemical compound C=12C=CCOC2=C(OC)C(OC)=CC=1CC1=CN=C(N)N=C1N NWFFAMNYFYKTDZ-UHFFFAOYSA-N 0.000 claims description 13
• 229910052760 oxygen Inorganic materials 0.000 claims description 13
• 125000004414 alkyl thio group Chemical group 0.000 claims description 12
• YZCKVEUIGOORGS-IGMARMGPSA-N Protium Chemical compound [1H] YZCKVEUIGOORGS-IGMARMGPSA-N 0.000 claims description 11
• 125000003545 alkoxy group Chemical group 0.000 claims description 11
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
• 150000001721 carbon Chemical group 0.000 claims description 11
• 239000001301 oxygen Substances 0.000 claims description 11
• CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 10
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 10
• 125000000217 alkyl group Chemical group 0.000 claims description 10
• SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 10
• MMDZZHAZMNJFMW-UHFFFAOYSA-N (2,4-diaminopyrimidin-5-yl)methanol Chemical compound NC1=NC=C(CO)C(N)=N1 MMDZZHAZMNJFMW-UHFFFAOYSA-N 0.000 claims description 9
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 8
• 125000003342 alkenyl group Chemical group 0.000 claims description 8
• 238000007327 hydrogenolysis reaction Methods 0.000 claims description 8
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical class C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 6
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical class C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 6
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
• 125000000623 heterocyclic group Chemical group 0.000 claims description 6
• 125000003277 amino group Chemical group 0.000 claims description 5
• 239000003795 chemical substances by application Substances 0.000 claims description 5
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
• WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical compound [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 claims description 5
• DCTFGGVNZYFNGJ-UHFFFAOYSA-N 5-[(2,4-diaminopyrimidin-5-yl)methyl]-7-methoxyquinolin-8-ol Chemical compound C=12C=CC=NC2=C(O)C(OC)=CC=1CC1=CN=C(N)N=C1N DCTFGGVNZYFNGJ-UHFFFAOYSA-N 0.000 claims description 4
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 4
• 229910021529 ammonia Inorganic materials 0.000 claims description 4
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
• 229910052717 sulfur Inorganic materials 0.000 claims description 4
• OQZGLXOADHKTDN-UHFFFAOYSA-N 1-oxidopyrimidin-1-ium Chemical compound [O-][N+]1=CC=CN=C1 OQZGLXOADHKTDN-UHFFFAOYSA-N 0.000 claims description 3
• SNBAXPMOWGZMOL-UHFFFAOYSA-N 5-[(2,4-diaminopyrimidin-5-yl)methyl]-7,8-dimethoxychromen-2-one Chemical compound C=12C=CC(=O)OC2=C(OC)C(OC)=CC=1CC1=CN=C(N)N=C1N SNBAXPMOWGZMOL-UHFFFAOYSA-N 0.000 claims description 3
• YXVYIKAJJZFIQN-UHFFFAOYSA-N 5-[(7,8-dimethoxy-2-methyl-2h-chromen-5-yl)methyl]pyrimidine-2,4-diamine Chemical compound C=12C=CC(C)OC2=C(OC)C(OC)=CC=1CC1=CN=C(N)N=C1N YXVYIKAJJZFIQN-UHFFFAOYSA-N 0.000 claims description 3
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 3
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 3
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
• 125000002490 anilino group Chemical class [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 3
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
• 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 3
• 239000011593 sulfur Substances 0.000 claims description 3
• RUFPHBVGCFYCNW-UHFFFAOYSA-N 1-naphthylamine Chemical compound C1=CC=C2C(N)=CC=CC2=C1 RUFPHBVGCFYCNW-UHFFFAOYSA-N 0.000 claims description 2
• GKQJABQIIZIFFZ-UHFFFAOYSA-N 5-[(4-amino-3-methoxynaphthalen-1-yl)methyl]pyrimidine-2,4-diamine Chemical compound C=12C=CC=CC2=C(N)C(OC)=CC=1CC1=CN=C(N)N=C1N GKQJABQIIZIFFZ-UHFFFAOYSA-N 0.000 claims description 2
• ZCONNBVJQVEVEB-UHFFFAOYSA-N 5-[(7-methoxy-8-nitroquinolin-5-yl)methyl]pyrimidine-2,4-diamine Chemical compound C=12C=CC=NC2=C([N+]([O-])=O)C(OC)=CC=1CC1=CN=C(N)N=C1N ZCONNBVJQVEVEB-UHFFFAOYSA-N 0.000 claims description 2
• GVNXJSKJOJYPOC-UHFFFAOYSA-N 5-[(8-amino-7-methoxyquinolin-5-yl)methyl]pyrimidine-2,4-diamine Chemical compound C=12C=CC=NC2=C(N)C(OC)=CC=1CC1=CN=C(N)N=C1N GVNXJSKJOJYPOC-UHFFFAOYSA-N 0.000 claims description 2
• GEZCGCFDXURYSM-UHFFFAOYSA-N 5-[(8-amino-7-methylsulfanylquinolin-5-yl)methyl]pyrimidine-2,4-diamine Chemical compound C=12C=CC=NC2=C(N)C(SC)=CC=1CC1=CN=C(N)N=C1N GEZCGCFDXURYSM-UHFFFAOYSA-N 0.000 claims description 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
• WZKSXHQDXQKIQJ-UHFFFAOYSA-N F[C](F)F Chemical compound F[C](F)F WZKSXHQDXQKIQJ-UHFFFAOYSA-N 0.000 claims description 2
• 125000003302 alkenyloxy group Chemical group 0.000 claims description 2
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
• 125000003282 alkyl amino group Chemical group 0.000 claims description 2
• AIOWJIMWVFWROP-UHFFFAOYSA-N baquiloprim Chemical compound C12=CC=CN=C2C(N(C)C)=C(C)C=C1CC1=CN=C(N)N=C1N AIOWJIMWVFWROP-UHFFFAOYSA-N 0.000 claims description 2
• 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
• 238000007068 beta-elimination reaction Methods 0.000 claims description 2
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
• 150000002357 guanidines Chemical class 0.000 claims description 2
• 125000005905 mesyloxy group Chemical group 0.000 claims description 2
• 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
• 125000005415 substituted alkoxy group Chemical group 0.000 claims description 2
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 2
• 238000006467 substitution reaction Methods 0.000 claims description 2
• 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 2
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 2
• 125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 claims description 2
• 150000002431 hydrogen Chemical class 0.000 claims 6
• 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims 1
• URPGJMLVVSCAKX-UHFFFAOYSA-N 5-[(7,8-dimethoxy-2-methyl-4h-chromen-5-yl)methyl]pyrimidine-2,4-diamine Chemical compound C=12CC=C(C)OC2=C(OC)C(OC)=CC=1CC1=CN=C(N)N=C1N URPGJMLVVSCAKX-UHFFFAOYSA-N 0.000 claims 1
• OQFGIDFOQYUQAF-UHFFFAOYSA-N 5-[(7,8-dimethoxy-3,4-dihydro-2h-chromen-5-yl)methyl]pyrimidine-2,4-diamine Chemical compound C=12CCCOC2=C(OC)C(OC)=CC=1CC1=CN=C(N)N=C1N OQFGIDFOQYUQAF-UHFFFAOYSA-N 0.000 claims 1
• UEZUWFLRLFLRDB-UHFFFAOYSA-N 5-[(7,8-dimethoxyquinolin-5-yl)methyl]pyrimidine-2,4-diamine Chemical compound C=12C=CC=NC2=C(OC)C(OC)=CC=1CC1=CN=C(N)N=C1N UEZUWFLRLFLRDB-UHFFFAOYSA-N 0.000 claims 1
• DDYFWXNCUMRKPM-UHFFFAOYSA-N 5-[(7-methylquinolin-5-yl)methyl]pyrimidine-2,4-diamine Chemical compound C=12C=CC=NC2=CC(C)=CC=1CC1=CN=C(N)N=C1N DDYFWXNCUMRKPM-UHFFFAOYSA-N 0.000 claims 1
• 101100260565 Dictyostelium discoideum thyA gene Proteins 0.000 claims 1
• QXKHYNVANLEOEG-UHFFFAOYSA-N Methoxsalen Chemical group C1=CC(=O)OC2=C1C=C1C=COC1=C2OC QXKHYNVANLEOEG-UHFFFAOYSA-N 0.000 claims 1
• JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical class O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims 1
• ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 claims 1
• 230000000269 nucleophilic effect Effects 0.000 claims 1
• 238000001275 scanning Auger electron spectroscopy Methods 0.000 claims 1
• 101150068774 thyX gene Proteins 0.000 claims 1
• 125000005490 tosylate group Chemical class 0.000 claims 1
• 229940124530 sulfonamide Drugs 0.000 abstract description 10
• 150000003456 sulfonamides Chemical class 0.000 abstract description 7
• 230000000844 anti-bacterial effect Effects 0.000 abstract description 6
• 230000009044 synergistic interaction Effects 0.000 abstract description 2
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 211
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 84
• 238000004458 analytical method Methods 0.000 description 79
• 239000000243 solution Substances 0.000 description 77
• 239000000203 mixture Substances 0.000 description 70
• 239000007787 solid Substances 0.000 description 58
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 53
• 239000000047 product Substances 0.000 description 50
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 45
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 28
• 238000001953 recrystallisation Methods 0.000 description 27
• 238000010992 reflux Methods 0.000 description 26
• 239000000460 chlorine Substances 0.000 description 23
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 22
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
• IEDVJHCEMCRBQM-UHFFFAOYSA-N trimethoprim Chemical compound COC1=C(OC)C(OC)=CC(CC=2C(=NC(N)=NC=2)N)=C1 IEDVJHCEMCRBQM-UHFFFAOYSA-N 0.000 description 20
• 229960000583 acetic acid Drugs 0.000 description 19
• 239000002244 precipitate Substances 0.000 description 19
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
• 229960005404 sulfamethoxazole Drugs 0.000 description 17
• JLKIGFTWXXRPMT-UHFFFAOYSA-N sulphamethoxazole Chemical compound O1C(C)=CC(NS(=O)(=O)C=2C=CC(N)=CC=2)=N1 JLKIGFTWXXRPMT-UHFFFAOYSA-N 0.000 description 17
• 229960001082 trimethoprim Drugs 0.000 description 17
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 16
• 239000003921 oil Substances 0.000 description 15
• 235000019198 oils Nutrition 0.000 description 15
• 238000005481 NMR spectroscopy Methods 0.000 description 13
• 238000009835 boiling Methods 0.000 description 13
• 229940125904 compound 1 Drugs 0.000 description 13
• 239000000843 powder Substances 0.000 description 13
• 239000000725 suspension Substances 0.000 description 13
• 239000002904 solvent Substances 0.000 description 12
• 238000000746 purification Methods 0.000 description 11
• 239000011541 reaction mixture Substances 0.000 description 11
• 238000011282 treatment Methods 0.000 description 11
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
• 239000002253 acid Substances 0.000 description 10
• 239000012362 glacial acetic acid Substances 0.000 description 10
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
• SEEPANYCNGTZFQ-UHFFFAOYSA-N sulfadiazine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)NC1=NC=CC=N1 SEEPANYCNGTZFQ-UHFFFAOYSA-N 0.000 description 10
• 229960004306 sulfadiazine Drugs 0.000 description 10
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 9
• 239000003814 drug Substances 0.000 description 9
• 239000000706 filtrate Substances 0.000 description 9
• 229960004198 guanidine Drugs 0.000 description 9
• DRGCXLJWMQGVJA-UHFFFAOYSA-N pyrimidine;dihydrochloride Chemical compound Cl.Cl.C1=CN=CN=C1 DRGCXLJWMQGVJA-UHFFFAOYSA-N 0.000 description 9
• 238000003756 stirring Methods 0.000 description 9
• 241000283690 Bos taurus Species 0.000 description 8
• 239000004480 active ingredient Substances 0.000 description 8
• 244000309466 calf Species 0.000 description 8
• 238000009472 formulation Methods 0.000 description 8
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
• 239000002585 base Substances 0.000 description 7
• 229960000789 guanidine hydrochloride Drugs 0.000 description 7
• PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 7
• 239000004615 ingredient Substances 0.000 description 7
• 238000004949 mass spectrometry Methods 0.000 description 7
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 7
• 239000012044 organic layer Substances 0.000 description 7
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 7
• 239000000741 silica gel Substances 0.000 description 7
• 229910002027 silica gel Inorganic materials 0.000 description 7
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 6
• 238000005160 1H NMR spectroscopy Methods 0.000 description 6
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
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• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 6
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
• 239000002775 capsule Substances 0.000 description 6
• 239000003054 catalyst Substances 0.000 description 6
• 238000001816 cooling Methods 0.000 description 6
• 239000012458 free base Substances 0.000 description 6
• TUJKJAMUKRIRHC-UHFFFAOYSA-N hydroxyl Chemical compound [OH] TUJKJAMUKRIRHC-UHFFFAOYSA-N 0.000 description 6
• 239000008101 lactose Substances 0.000 description 6
• GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 6
• 239000008194 pharmaceutical composition Substances 0.000 description 6
• 230000009467 reduction Effects 0.000 description 6
• 239000000523 sample Substances 0.000 description 6
• 239000006188 syrup Substances 0.000 description 6
• 235000020357 syrup Nutrition 0.000 description 6
• XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 5
• HWBPOLWLLFXEJY-UHFFFAOYSA-N 3'-Hydroxytrimethoprim Chemical compound OC1=C(OC)C(OC)=CC(CC=2C(=NC(N)=NC=2)N)=C1 HWBPOLWLLFXEJY-UHFFFAOYSA-N 0.000 description 5
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
• 239000000654 additive Substances 0.000 description 5
• 238000002425 crystallisation Methods 0.000 description 5
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• 239000003937 drug carrier Substances 0.000 description 5
• 230000000694 effects Effects 0.000 description 5
• 238000001704 evaporation Methods 0.000 description 5
• 230000008020 evaporation Effects 0.000 description 5
• 239000007924 injection Substances 0.000 description 5
• 238000002347 injection Methods 0.000 description 5
• 235000019359 magnesium stearate Nutrition 0.000 description 5
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