Maleic Acid → HCID 178488218, compound

HRID 897571Notes

Reaction equation

HRID 897571 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@H:33]3[CH2:38][CH2:37][C@H:36]([N: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].[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@H:33]3[CH2:34][CH2:35][C@H:36]([N: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

Participants

4

Reactant 2

HCID 444266Maleic AcidHCID 178488217HCID 178488217, compound

Product 1

HCID 178488218HCID 178488218, compoundYield 109.4%

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-(trifluoromethoxy)benzamide (520 mg, 0.832 mmol) was dissolved in hot ethyl acetate (55 mL) and maleic acid (290 mg, 2.497 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 to give trans-N1-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-4-(trifluoromethoxy)benzamide, dimaleate salt (780 mg, 96%). 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), 6.18 (s, 6H), 7.28 (d, J=8.14 Hz, 1H), 7.33 (s, 1H), 7.54 (d, J=8.47 Hz, 2H), 8.01 (d, J=8.12 Hz, 1H), 8.10 (d, J=8.69 Hz, 2H), 8.26 (s, 1H), 9.69 (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+=625.4, Rt=2.21 min.

Workup

  1. filtrationThe solid was collected by filtration

Sources & evidence

ORD record
ord-09ecc73998744cdcbeca84d620bfb3b0
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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