Cesium carbonate → HCID 131725046, compound

HRID 2056151Notes

Reaction equation

HRID 2056151 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:33]3[CH2:38][CH2:37][NH:36][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]([C:25]([F:28])([F:27])[F:26])=[CH:21][C:20]=4[F:29])=[C:13]([O:31][CH3:32])[CH:12]=3)[C:3]=12.Br[CH2:40][C:41]([NH2:43])=[O:42].[C:44](=[O:47])([O-])[O-:45].[Cs+].[Cs+]>CN(C=O)C>[C:18]([OH:30])(=[O:42])[CH3:19].[NH3:1].[C:44]([OH:45])(=[O:47])[CH3:2].[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:33]3[CH2:38][CH2:37][N:36]([CH2:40][C:41]([NH2:43])=[O:42])[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]([C:25]([F:28])([F:26])[F:27])=[CH:21][C:20]=4[F:29])=[C:13]([O:31][CH3:32])[CH:12]=3)[C:3]=12

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 696322-BromoacetamideHCID 22346947HCID 22346947, compound

Product 2

HCID 12432Ammonia acetateHCID 131725046HCID 131725046, compoundYield 114.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N1-{4-[4-amino-1-(4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-2-fluoro-4-(trifluoromethyl)benzamide (100 g, 0.189 mmol), 2-bromoacetamide (28 mg, 0.208 mmol) and cesium carbonate (123 mg, 0.378 mmol) was mixed in DMF (2 mL). The mixture was stirred at room temperature overnight. The crude mixture was purified by reverse phase preparative HPLC (Rainin HPLC, Column: Thermoquest, hyperprep HS C18, 8 um, 250×21.2 mm. Eluents: 5% B/A to 100% B/A in 25 min. (B: acetonitrile, A: 50 mM ammonia acetate buffer, pH 4.5), 21 mL/min.) to give N1-(4-{4-amino-1-[1-(2-amino-2-oxoethyl)-4-piperidyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-2-fluoro-4-(trifluoromethyl)benzamide, acetate salt (70 mg, 63%). 1H NMR (DMSO-d6) δ 1.90 (m, 5H), 2.34 (m, 4H), 2.93 (s, 2H), 2.99 (m, 2H), 3.94 (s, 3H), 4.69 (m, 1H), 7.12 (s, 1H), 7.25 (s, 1H), 7.30 (d, J=8.15 Hz, 1H), 7.34 (s, 1H), 7.75 (d, J=8.15 Hz, 1H), 7.87 (d, J=10.30 Hz, 1H), 7.99 (m, 1H), 8.25 (s, 1H), 8.31 (d, J=8.14 Hz, 1H), 9.90 (s, 1H). LCMS (Thermoquest AQA single Quad MS, Finnigan HPLC-Column: Genesis, C18, 3 um, 33×4.6 mm. Eluents: 30% B/A to 95% B/A in 4.5 min. (B: acetonitrile, A: 50 mM ammonia acetate buffer, pH 4.5), 0.8 mL/min.): MH+=587.2, Rt=2.17 min.

Workup

  1. customThe crude mixture was purified by reverse phase preparative HPLC (Rainin HPLC, Column
  2. waitEluents: 5% B/A to 100% B/A in 25 min. (B

Sources & evidence

ORD record
ord-e980a6afc01b4fef9cd99c234fd1bfad
Source dataset
uspto-grants-2008_02
Patent number
US07332497B2

Reaction notes

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