Maleic Acid → N2-(4-{4-amino-1-[2-(4-methylpiperazino)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-1-methyl-1H-2-indolecarboxamide trimaleate

HRID 897834Notes

Reaction equation

HRID 897834 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:32][CH2:33][N:34]3[CH2:39][CH2:38][N:37]([CH3:40])[CH2:36][CH2:35]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]4[N:21]([CH3:29])[C:22]5[C:27]([CH:28]=4)=[CH:26][CH:25]=[CH:24][CH:23]=5)=[O:19])=[C:13]([O:30][CH3:31])[CH:12]=3)[C:3]=12.[C:41]([OH:48])(=[O:47])/[CH:42]=[CH:43]\[C:44]([OH:46])=[O:45]>C(OCC)(=O)C>[C:41]([OH:48])(=[O:47])/[CH:42]=[CH:43]\[C:44]([OH:46])=[O:45].[C:41]([OH:48])(=[O:47])/[CH:42]=[CH:43]\[C:44]([OH:46])=[O:45].[C:41]([OH:48])(=[O:47])/[CH:42]=[CH:43]\[C:44]([OH:46])=[O:45].[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:32][CH2:33][N:34]3[CH2:35][CH2:36][N:37]([CH3:40])[CH2:38][CH2:39]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]4[N:21]([CH3:29])[C:22]5[C:27]([CH:28]=4)=[CH:26][CH:25]=[CH:24][CH:23]=5)=[O:19])=[C:13]([O:30][CH3:31])[CH:12]=3)[C:3]=12

Participants

4

Reactant 2

HCID 444266Maleic AcidHCID 22347346N2-(4-{4-amino-1-[2-(4-methylpiperazino)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-1-methyl-1H-2-indolecarboxamide

Product 1

HCID 86586280N2-(4-{4-amino-1-[2-(4-methylpiperazino)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-1-methyl-1H-2-indolecarboxamide trimaleateYield 66.7%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

To a mixture of N2-(4-{4-amino-1-[2-(4-methylpiperazino)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-1-methyl-1H-2-indolecarboxamide (0.082 g, 0.15 mmol) in warm ethyl acetate (2 mL) was added a solution of maleic acid (0.053 g, 0.46 mmol) in warm ethyl acetate (1 mL). A precipitate formed immediately. The reaction mixture was allowed to cool to ambient temperature and the precipitate was collected by filtration, washed with ethyl acetate (5 mL), and dried in vacuo to afford N2-(4-{4-amino-1-[2-(4-methylpiperazino)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-1-methyl-1H-2-indolecarboxamide trimaleate as a beige solid (0.090 g, 0.10 mmol): 1H NMR (d6-DMSO, 400 MHz): δH 9.45 (1H, s), 8.27 (1H, s), 8.12 (1H, d, J=8.0 Hz), 7.71 (1H, d, J=8.0 Hz), 7.59 (1H, d, J=8.0 Hz), 7.29-7.36 (4H, m), 7.15 (1H, t, J=7.4 Hz), 6.17 (6H, s), 4.50 (2H, t, J=6.4 Hz), 4.04 (3H, s), 3.96 (3H, s), 3.10-3.20 (4H, m), 2.92-2.95 (4H, m), 2.74 (3H, s), and 2.32-2.37 (2H, m); RP-HPLC (Hypersil C18, 5 μm, 100 Å, 15 cm; 5%-100% acetonitrile-0.1 M ammonium acetate over 15 min, 1 mL/min). Rt 10.48 min. MS: M+ 540.3.

Workup

  1. customA precipitate formed immediately
  2. filtrationthe precipitate was collected by filtration
  3. washwashed with ethyl acetate (5 mL)
  4. customdried in vacuo

Sources & evidence

ORD record
ord-86e22298bd094dfa92380f7c5c7e266d
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

Loading…