Maleic Acid → N2-(4-{4-amino-1-[1-(2,2-difluoroethyl)-4-piperidyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-1-methyl-1H-2-indolecarboxamide, dimaleate salt

HRID 2056191Notes

Reaction equation

HRID 2056191 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]([CH2:38][CH:39]([F:41])[F:40])[CH2:34][CH2:33]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:42]([OH:49])(=[O:48])/[CH:43]=[CH:44]\[C:45]([OH:47])=[O:46]>C(OCC)(=O)C>[C:42]([OH:49])(=[O:48])/[CH:43]=[CH:44]\[C:45]([OH:47])=[O:46].[C:42]([OH:49])(=[O:48])/[CH:43]=[CH:44]\[C:45]([OH:47])=[O:46].[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]([CH2:38][CH:39]([F:40])[F:41])[CH2:34][CH2:33]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 22347012N2-(4-{4-amino-1-[1-(2,2-difluoroethyl)-4-piperidyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-1-methyl-1H-2-indolecarboxamide

Product 1

HCID 131725051N2-(4-{4-amino-1-[1-(2,2-difluoroethyl)-4-piperidyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-1-methyl-1H-2-indolecarboxamide, dimaleate saltYield 68.5%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

N2-(4-{4-amino-1-[1-(2,2-difluoroethyl)-4-piperidyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-1-methyl-1H-2-indolecarboxamide (227 mg, 0.405 mmol) was dissolved in hot ethyl acetate (25 mL). Maleic acid (94 mg, 0.810 mmol) in hot ethyl acetate (3 mL) was added. The reaction mixture was stirred at room temperature overnight. No precipitate was formed. After stirring at room temperature for 4 days, precipitate was formed at bottom of the flask. The solvent was decanted. The solid was washed with ethyl acetate and dried to give N2-(4-{4-amino-1-[1-(2,2-difluoroethyl)-4-piperidyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-1-methyl-1H-2-indolecarboxamide, dimaleate salt (220 mg, 68%).

Workup

  1. customNo precipitate was formed
  2. stirringAfter stirring at room temperature for 4 days
  3. customprecipitate was formed at bottom of the flask
  4. customThe solvent was decanted
  5. washThe solid was washed with ethyl acetate
  6. customdried

Sources & evidence

ORD record
ord-028d707eb71c48fcb450cc81b5eb24ef
Source dataset
uspto-grants-2008_02
Patent number
US07332497B2

Reaction notes

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