Maleic Acid → HCID 178488215, compound

HRID 897570Notes

Reaction equation

HRID 897570 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@H:32]3[CH2:37][CH2:36][C@H:35]([N:38]4[CH2:43][CH2:42][N:41]([CH3:44])[CH2:40][CH2:39]4)[CH2:34][CH2:33]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:29])[C:19]4[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=4)=[C:13]([O:30][CH3:31])[CH:12]=3)[C:3]=12.[C:45]([OH:52])(=[O:51])/[CH:46]=[CH:47]\[C:48]([OH:50])=[O:49]>C(OCC)(=O)C>[C:45]([OH:52])(=[O:51])/[CH:46]=[CH:47]\[C:48]([OH:50])=[O:49].[C:45]([OH:52])(=[O:51])/[CH:46]=[CH:47]\[C:48]([OH:50])=[O:49].[C:45]([OH:52])(=[O:51])/[CH:46]=[CH:47]\[C:48]([OH:50])=[O:49].[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@H:32]3[CH2:33][CH2:34][C@H:35]([N:38]4[CH2:39][CH2:40][N:41]([CH3:44])[CH2:42][CH2:43]4)[CH2:36][CH2:37]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18](=[O:29])[C:19]4[CH:20]=[CH:21][C:22]([C:25]([F:26])([F:28])[F:27])=[CH:23][CH:24]=4)=[C:13]([O:30][CH3:31])[CH:12]=3)[C:3]=12

Participants

4

Reactant 2

HCID 444266Maleic AcidHCID 178488213HCID 178488213, compound

Product 1

HCID 178488215HCID 178488215, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

trans-N1-(4-{4-Amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-4-(trifluoromethyl)benzamide (510 mg, 0.838 mmol) was dissolved in hot ethyl acetate (55 mL) and maleic acid (292 mg, 2.513 mmol) in hot ethyl acetate (5 mL) was added. The reaction mixture was stirred at room temperature for 5 hours. The solid was collected by filtration trans-N1-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-4-(trifluoromethyl)benzamide, dimaleate salt (802 mg, 100%). 1H NMR (DMSO-d6) δ 1.60 (m, 2H), 2.06 (m, 6H), 2.68 (s, 3H), 2.83-3.17 (bm, 9H), 3.93 (s, 3H), 4.72 (m, 1H), 6.17 (s, 6H), 7.29 (d, J=8.12 Hz, 1H), 7.33 (s, 1H), 7.92 (d, J=8.34 Hz, 2H), 8.02 (d, J=8.12 Hz, 1H), 8.17 (d, J=8.12 Hz, 2H), 8.26 (s, 1H), 9.83 (s, 1H). LCMS (Finigan-Column: Pecosphere, C18, 3 um, 33×4.6 mm. Eluents: 0% B/A to 100% B/A in 4 min. (B: acetonitrile, A: 50 mM ammonia acetate buffer, pH 4.5), 3.0 mL/min.): MH+=609.4, Rt=2.16 min.

Workup

  1. filtrationThe solid was collected by filtration trans-N1-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-4-(trifluoromethyl)benzamide, dimaleate salt (802 mg, 100%)
  2. waitEluents: 0% B/A to 100% B/A in 4 min. (B

Sources & evidence

ORD record
ord-74e615bb8c994d9a96be2c2e94749c2e
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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