Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → HCID 59011648, compound

HRID 492893Notes

Reaction equation

HRID 492893 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([N:11]=[C:12]=[S:13])=[O:10])=[CH:4][CH:3]=1.[NH2:14][C:15]1[CH:43]=[CH:42][C:18]([O:19][C:20]2[CH:25]=[C:24]([NH:26][C:27]([N:29]3[CH2:34][CH2:33][CH:32]([N:35]4[CH2:40][CH2:39][N:38]([CH3:41])[CH2:37][CH2:36]4)[CH2:31][CH2:30]3)=[O:28])[N:23]=[CH:22][N:21]=2)=[C:17]([F:44])[CH:16]=1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>C1(C)C=CC=CC=1.C(O)C>[F:44][C:17]1[CH:16]=[C:15]([NH:14][C:12]([NH:11][C:9](=[O:10])[CH2:8][C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)=[S:13])[CH:43]=[CH:42][C:18]=1[O:19][C:20]1[CH:25]=[C:24]([NH:26][C:27]([N:29]2[CH2:30][CH2:31][CH:32]([N:35]3[CH2:40][CH2:39][N:38]([CH3:41])[CH2:37][CH2:36]3)[CH2:33][CH2:34]2)=[O:28])[N:23]=[CH:22][N:21]=1

Participants

6

Reactant 3

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 231531584-(4-Amino-2-fluorophenoxy)-6-{[4-(1-methylpiperazin-4-yl)piperidin-1-yl]carbonylamino}pyrimidineHCID 231532482-(4-Fluorophenyl)acetyl isothiocyanate

Product 1

HCID 59011648HCID 59011648, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 1140TolueneSolvent

Procedure

After adding a solution of 2-(4-fluorophenyl)acetyl isothiocyanate in toluene (0.25 M, 2.0 ml) to a solution of 4-(4-amino-2-fluorophenoxy)-6-{[4-(1-methylpiperazin-4-yl)piperidin-1-yl]carbonylamino}pyrimidine (98 mg) and (+)-10-camphorsulfonic acid (79 mg) in ethanol (2.0 ml) at room temperature, the mixture was stirred for 3.5 hours. The reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium hydrogencarbonate. The organic layer was washed with saturated aqueous sodium hydrogencarbonate and brine and dried over anhydrous sodium sulfate. The solvent was then distilled off, and the residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate, then ethyl acetate:methanol=97:3) to provide the title compound (65.2 mg, 46%) as white powder.

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium hydrogencarbonate
  2. washThe organic layer was washed with saturated aqueous sodium hydrogencarbonate and brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. distillationThe solvent was then distilled off
  5. customthe residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent

Sources & evidence

ORD record
ord-e9c892cfa15c42e0813715bb85fcc258
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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