Potassium Carbonate → 2-{2-[5-(4-Methyl-piperazin-1-yl)-2-trifluoromethoxy-phenylamino]-pyrimidin-4-yl}-4-oxo-1-(2,2,2-trifluoro-ethyl)-1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-carboxylic acid tert-butyl ester

HRID 1968561Notes

Reaction equation

HRID 1968561 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:9]=[CH:10][C:11]([O:15][C:16]([F:19])([F:18])[F:17])=[C:12]([NH2:14])[CH:13]=2)[CH2:4][CH2:3]1.[C:20]([O:24][C:25]([N:27]1[CH2:32][CH2:31][C:30]2[N:33]([CH2:43][C:44]([F:47])([F:46])[F:45])[C:34]([C:36]3[CH:41]=[CH:40][N:39]=[C:38](I)[N:37]=3)=[CH:35][C:29]=2[C:28]1=[O:48])=[O:26])([CH3:23])([CH3:22])[CH3:21].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:20]([O:24][C:25]([N:27]1[CH2:32][CH2:31][C:30]2[N:33]([CH2:43][C:44]([F:46])([F:45])[F:47])[C:34]([C:36]3[CH:41]=[CH:40][N:39]=[C:38]([NH:14][C:12]4[CH:13]=[C:8]([N:5]5[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]5)[CH:9]=[CH:10][C:11]=4[O:15][C:16]([F:19])([F:17])[F:18])[N:37]=3)=[CH:35][C:29]=2[C:28]1=[O:48])=[O:26])([CH3:23])([CH3:21])[CH3:22]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 249941425-(4-Methylpiperazin-1-yl)-2-trifluoromethoxyphenylamineHCID 866651442-(2-Iodo-pyrimidin-4-yl)-4-oxo-1-(2,2,2-trifluoro-ethyl)-1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-carboxylic acid tert-butyl ester

Product 1

HCID 866651452-{2-[5-(4-Methyl-piperazin-1-yl)-2-trifluoromethoxy-phenylamino]-pyrimidin-4-yl}-4-oxo-1-(2,2,2-trifluoro-ethyl)-1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-carboxylic acid tert-butyl esterYield 25%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent2×

Procedure

Palladium acetate [Pd(OAc)2] (4 mg, 0.015 mmol), (±)-BINAP (9 mg, 0.015 mmol) and dimethylformamide (1 mL) were charged to a round-bottom flask flushed with argon. The flask was evacuated and backfilled with argon. The mixture was stirred under argon for 30 minutes and added to a mixture of 5-(4-methyl-piperazin-1-yl)-2-trifluoromethoxy-phenylamine (50 mg, 0.18 mmol), 2-(2-iodo-pyrimidin-4-yl)-4-oxo-1-(2,2,2-trifluoro-ethyl)-1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-carboxylic acid tert-butyl ester (80 m, 0.15 mmol), and potassium carbonate (205 g, 1.50 mmol) in dimethylformamide (3 mL). The resulting mixture was stirred at 80° C. for 2 hours under argon. After cooling to room temperature, the reaction mixture was filtered on a pad of celite. The solvent was concentrated, the crude solid was purified by flash chromatography on silica gel (eluant: dichloromethane/methanol 9/1) to afford 25 mg (25%) of the title compound as white solid.

Workup

  1. customflushed with argon
  2. customThe flask was evacuated
  3. stirringThe resulting mixture was stirred at 80° C. for 2 hours under argon
  4. filtrationthe reaction mixture was filtered on a pad of celite
  5. concentrationThe solvent was concentrated
  6. customthe crude solid was purified by flash chromatography on silica gel (eluant: dichloromethane/methanol 9/1)

Sources & evidence

ORD record
ord-58456dabbf13489ca142fe7e96f8fa9a
Source dataset
uspto-grants-2013_04
Patent number
US08426417B2

Reaction notes

Loading…