Maleic Acid → HCID 178488230, 화합물

HRID 897692

반응식

HRID 897692 반응식
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@H:31]3[CH2:36][CH2:35][C@H:34]([N:37]4[CH2:42][CH2:41][N:40]([CH3:43])[CH2:39][CH2:38]4)[CH2:33][CH2:32]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]([C@H:20]4[CH2:22][C@@H:21]4[C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[O:19])=[C:13]([O:29][CH3:30])[CH:12]=3)[C:3]=12.[C:44]([OH:51])(=[O:50])/[CH:45]=[CH:46]\[C:47]([OH:49])=[O:48]>C(OCC)(=O)C>[C:44]([OH:51])(=[O:50])/[CH:45]=[CH:46]\[C:47]([OH:49])=[O:48].[C:44]([OH:51])(=[O:50])/[CH:45]=[CH:46]\[C:47]([OH:49])=[O:48].[C:44]([OH:51])(=[O:50])/[CH:45]=[CH:46]\[C:47]([OH:49])=[O:48].[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@H:31]3[CH2:32][CH2:33][C@H:34]([N:37]4[CH2:38][CH2:39][N:40]([CH3:43])[CH2:41][CH2:42]4)[CH2:35][CH2:36]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]([C@H:20]4[CH2:22][C@@H:21]4[C:23]4[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=4)=[O:19])=[C:13]([O:29][CH3:30])[CH:12]=3)[C:3]=12

참가 물질

4

반응물 2

HCID 444266Maleic AcidHCID 178488229HCID 178488229, 화합물

생성물 1

HCID 178488230HCID 178488230, 화합물수율 86.8%

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매2회

실험 절차

A solution of trans-3-(4-amino-3-methoxyphenyl)-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.162 g, 0.371 mmol) in pyridine (2 mL) at 0° C. was treated with trans-2-phenyl-1-cyclopropylcarbonyl chloride (0.134 g, 0.742 mmol) under a nitrogen atmosphere. The reaction mixture was stirred for 20 min at 0° C., the ice bath was removed and the reaction mixture stirred at room temperature for 5 h. Additional trans-2-phenyl-1-cyclopropylcarbonyl chloride (0.034 g, 0.186 mmol) was added and the reaction mixture stirred for 1 h. The organic layer was removed under reduced pressure, and dichloromethane (15 mL) was then added. The layers were separated using an Empore extraction cartridge. The organic layer was removed under reduced pressure. The crude product was purified by flash chromatography on silica gel using 15% methanol in dichloromethane then 20% methanol in dichloromethane as eluent. The column afforded 0.150 g (70%) of trans-N1-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-(1S,2S)-2-phenylcyclopropane-1-carboxamide. A hot solution of trans-N1-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-(1S,2S)-2-phenylcyclopropane-1-carboxamide (0.147, 0.253 mmol) in ethyl acetate was treated with a hot solution of maleic acid (0.088 g, 0.759 mmol) in ethyl acetate. The precipitate formed was filtered under nitrogen and dried under high vacuum to give 0.204 g of trans-N1-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-(1S,2S)-2-phenylcyclopropane-1-carboxamide tris-maleate. 1H NMR (DMSO-d6, 400 MHz) δ 9.64 (s, 1H), 8.23-8.21 (m, 2H), 7.33-7.29 (m, 2H), 7.24-7.17 (m, 4H), 6.16 (s, 6H), 4.69-4.66 (m, 1H), 3.90 (s, 3H), 2.90-2.60 (m, 7H), 2.37-2.35 (m, 2H), 2.10-1.99 (m, 8H), 1.70-1.50 (m, 3H), 1.32 (m, 1H); HPLC Waters 2690 Alliance HPLC (Symmetry Shield RP18 3.5 μm, 2.1×50 mm; 5%-95% acetonitrile-0.1 M ammonium acetate over 15 min, 0.5 mL/min) Rt 5.346 min (97%).

후처리

  1. customThe precipitate formed
  2. filtrationwas filtered under nitrogen
  3. customdried under high vacuum

출처 및 근거

ORD 기록
ord-375ec7e2a2284aeb9ab0d0ca557e9f90
출처 데이터셋
uspto-grants-2005_07
특허 번호
US06921763B2

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