Maleic Acid → N1-{4-[4-amino-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-4-(trifluoromethyl)benzamide, trimaleate salt

HRID 432288Notes

Reaction equation

HRID 432288 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:32]3[CH2:37][CH2:36][N:35]([CH3:38])[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:39]([OH:46])(=[O:45])/[CH:40]=[CH:41]\[C:42]([OH:44])=[O:43]>C(OCC)(=O)C>[C:39]([OH:46])(=[O:45])/[CH:40]=[CH:41]\[C:42]([OH:44])=[O:43].[C:39]([OH:46])(=[O:45])/[CH:40]=[CH:41]\[C:42]([OH:44])=[O:43].[C:39]([OH:46])(=[O:45])/[CH:40]=[CH:41]\[C:42]([OH:44])=[O:43].[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:32]3[CH2:37][CH2:36][N:35]([CH3:38])[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:27])([F:28])[F:26])=[CH:21][CH:20]=4)=[C:13]([O:30][CH3:31])[CH:12]=3)[C:3]=12

Participants

4

Reactant 2

HCID 444266Maleic AcidHCID 22346829N1-{4-[4-amino-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-4-(trifluoromethyl)benzamide

Product 1

HCID 131724244N1-{4-[4-amino-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-4-(trifluoromethyl)benzamide, trimaleate saltYield 102.8%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

N1-{4-[4-Amino-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-4-(trifluoromethyl)benzamide (78 mg, 0.128 mmol) was dissolved in hot ethyl acetate (10 mL) and maleic acid (45 mg, 0.387 mmol) in hot ethyl acetate (1 mL) was added. The reaction mixture was stirred at room temperature for 5 hours. The solvent was removed and ethyl acetate was added and the solid was collected by filtration to give N1-{4-[4-amino-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-4-(trifluoromethyl)benzamide, trimaleate salt (115 mg, 94% ). 1H NMR (DMSO-d6) δ 1.87 (m, 2H), 2.24 (m, 4H), 2.79 (s, 3H), 3.01-3.57 (bm, 11H), 3.93 (s, 3H), 5.09 (m, 1H), 6.12 (s, 6H), 7.32 (m, 2H), 7.93 (d, J=8.37 Hz, 2H), 8.04 (d, J=8.11 Hz, 1H), 8.16 (d, J=8.18 Hz, 2H), 8.29 (s, 1H), 9.84 (s, 1H). LCMS (Micromass-Column: Pecosphere, C18, 3 um, 33×4.6 mm. Eluents: 0% B/A to 100% B/A in 4.5 min. (B: acetonitrile, A: 50 mM ammonia acetate buffer, PH 4.5), 3.5 mL/min.): MH+ =609.4, Rt=2.50 min.

Workup

  1. customThe solvent was removed
  2. additionethyl acetate was added
  3. filtrationthe solid was collected by filtration

Sources & evidence

ORD record
ord-dc1f0ca06d3844d39b69a0fb30a5ebac
Source dataset
uspto-grants-2003_12
Patent number
US06660744B1

Reaction notes

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