Potassium Carbonate → HCID 131725045, compound

HRID 897973Notes

Reaction equation

HRID 897973 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.[CH3:39][O:40][CH2:41][CH2:42]Br.[C:44](=[O:47])([O-])[O-:45].[K+].[K+]>CN(C=O)C>[C:18]([OH:30])(=[O:40])[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]([CH2:42][CH2:41][O:40][CH3:39])[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 11430Potassium CarbonateHCID 809722-Bromoethyl methyl etherHCID 22346947HCID 22346947, compound

Product 2

HCID 12432Ammonia acetateHCID 131725045HCID 131725045, compoundYield 122.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

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-bromoethyl methyl ether (20 uL, 0.208 mmol) and potassium carbonate (52 mg, 0.378 mmol) was mixed in DMF (2 mL). The mixture was heated at 65° C. 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-methoxyethyl)-4-piperidyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-2-fluoro-4-(trifluoromethyl)benzamide, acetate salt (75 mg, 68%). 1H NMR (DMSO-d6) δ 1.90 (m, 2H), 2.22 (m, 4H), 2.54 (m, 2H), 3.02 (m, 2H), 3.26 (s, 3H), 3.46 (m, 2H), 3.94 (m, s, 3H), 4.66 (m, 1H), 7.30 (d, J=8.19 Hz, 1H), 7.34 (s, 1H), 7.74 (d, J=7.84 Hz, 1H), 7.90 (d, J=10.33 Hz, 1H), 7.99 (m, 1H), 8.24 (s, 1H), 8.30 (d, J=8.23 Hz, 1H), 9.89 (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

Sources & evidence

ORD record
ord-0e034b1c95924fe195bba0cdbe4ae7b7
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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