Maleic Acid → N1-(4-{4-amino-1-[1-(1-methylpiperidin-4-yl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-4-(trifluoromethoxy)benzamide tris-maleate salt

HRID 432317노트

반응식

HRID 432317 반응식
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:33]3[CH2:38][CH2:37][N:36]([CH:39]4[CH2:44][CH2:43][N:42]([CH3:45])[CH2:41][CH2:40]4)[CH2:35][CH2:34]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:30])[C:19]4[CH:24]=[CH:23][C:22]([O:25][C:26]([F:29])([F:28])[F:27])=[CH:21][CH:20]=4)=[C:13]([O:31][CH3:32])[CH:12]=3)[C:3]=12.[C:46]([OH:53])(=[O:52])/[CH:47]=[CH:48]\[C:49]([OH:51])=[O:50]>C(OCC)(=O)C>[C:46]([OH:53])(=[O:52])/[CH:47]=[CH:48]\[C:49]([OH:51])=[O:50].[C:46]([OH:53])(=[O:52])/[CH:47]=[CH:48]\[C:49]([OH:51])=[O:50].[C:46]([OH:53])(=[O:52])/[CH:47]=[CH:48]\[C:49]([OH:51])=[O:50].[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:33]3[CH2:34][CH2:35][N:36]([CH:39]4[CH2:40][CH2:41][N:42]([CH3:45])[CH2:43][CH2:44]4)[CH2:37][CH2:38]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:30])[C:19]4[CH:24]=[CH:23][C:22]([O:25][C:26]([F:27])([F:29])[F:28])=[CH:21][CH:20]=4)=[C:13]([O:31][CH3:32])[CH:12]=3)[C:3]=12

참가 물질

4

반응물 2

HCID 444266Maleic AcidHCID 22347199N1-(4-{4-amino-1-[1-(1-methylpiperidin-4-yl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-4-(trifluoromethoxy)benzamide

생성물 1

HCID 86759303N1-(4-{4-amino-1-[1-(1-methylpiperidin-4-yl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-4-(trifluoromethoxy)benzamide tris-maleate salt

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매2회

실험 절차

A solution of 3-(4-amino-3-methoxyphenyl)-1-[1-(1-methylpiperidin-4-yl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.450 g, 1.03 mmol) in pyridine (8 mL) at −5° C. was treated with a solution of 4-(trifluoromethoxy)-1-benzenecarbonyl chloride (0.231 g, 1.03 mmol) in dichloromethane (2.5 mL) drop-wise. The reaction mixture was stirred at −5° C. for 30 min. The ice bath was removed and the reaction mixture was stirred at room temperature for 3 h. 1 N sodium hydroxide solution (10 mL) was added, and stirred for 1 h. The organic solvent was removed under reduced pressure. Dichloromethane (10 mL) was added and the layers were separated using an Empore extraction cartridge. The organic solvent was removed under reduced pressure and the crude compound was purified by flash chromatography on silica gel using 10% methanol in dichloromethane as eluent to give 0.430 g (67%) N1-(4-{4-amino-1-[1-(1-methylpiperidin-4-yl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-4-(trifluoromethoxy)benzamide. A hot solution of N1-(4-{4-amino-1-[1-(1-methylpiperidin-4-yl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-4-(trifluoromethoxy)benzamide (0.430 g, 0.688 mmol) in ethyl acetate (15 mL) was treated with a hot solution of maleic acid (0.240 g, 2.07 mmol) in ethyl acetate. A precipitate was formed, filtered under nitrogen, and dried under high vacuum to give N1-(4-{4-amino-1-[1-(1-methylpiperidin-4-yl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-4-(trifluoromethoxy)benzamide tris-maleate salt.

후처리

  1. customA precipitate was formed
  2. filtrationfiltered under nitrogen
  3. customdried under high vacuum

출처 및 근거

ORD 기록
ord-ac449ab40f68472388d1f568e10bbc47
출처 데이터셋
uspto-grants-2003_12
특허 번호
US06660744B1

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