Methyl iodide → N-(3-Chloro-4-fluorophenyl)-7-{(2E)-3-[(2S)-1-methylpyrrolidin-2-yl]prop-2-enoyl}-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4-amine

HRID 38573Notes

Reaction equation

HRID 38573 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:11]3[C:18]4[CH2:19][CH2:20][N:21]([C:23](=[O:31])/[CH:24]=[CH:25]/[C@@H:26]5[CH2:30][CH2:29][CH2:28][NH:27]5)[CH2:22][C:17]=4[S:16][C:12]=3[N:13]=[CH:14][N:15]=2)[CH:5]=[CH:6][C:7]=1[F:8].[C:32](=O)([O-])[O-].[K+].[K+].IC>CN(C=O)C.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:11]3[C:18]4[CH2:19][CH2:20][N:21]([C:23](=[O:31])/[CH:24]=[CH:25]/[C@@H:26]5[CH2:30][CH2:29][CH2:28][N:27]5[CH3:32])[CH2:22][C:17]=4[S:16][C:12]=3[N:13]=[CH:14][N:15]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 25222665HCID 25222665, compound

Product 1

HCID 25221099N-(3-Chloro-4-fluorophenyl)-7-{(2E)-3-[(2S)-1-methylpyrrolidin-2-yl]prop-2-enoyl}-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4-amineYield 13%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-(3-Chloro-4-fluorophenyl)-7-{(2E)-3-[(25)-pyrrolidin-2-yl]prop-2-enoyl}-5,6,7,8-tetrahydropyrido[4′,3′:4,5]thieno[2,3-d]pyrimidin-4-amine from Example 13 (60 mg, 0.13 mmol) in DMF (1 mL) was added potassium carbonate (27 mg, 0.20 mmol) and iodomethane (20 mg, 0.14 mmol), and the mixture was stirred overnight at rt. The reaction mixture was diluted with ethyl acetate and extracted with water. The organic layer was dried over sodium sulfate, and the solvent was removed in vacuo. The crude product was purified by column chromatography on silica gel (eluent: DCM/MeOH 10:1) to yield 8 mg (13%) of the title compound.

Workup

  1. extractionextracted with water
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. customthe solvent was removed in vacuo
  4. customThe crude product was purified by column chromatography on silica gel (eluent: DCM/MeOH 10:1)

Sources & evidence

ORD record
ord-3e0ac45d4e73494693531e1d3a1c3ce1
Source dataset
uspto-grants-2013_09
Patent number
US08524722B2

Reaction notes

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