Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → HCID 57677641, compound

HRID 492895Notes

Reaction equation

HRID 492895 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][N:32]([CH: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][N:32]([CH: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 23153066HCID 23153066, compoundHCID 231532482-(4-Fluorophenyl)acetyl isothiocyanate

Product 1

HCID 57677641HCID 57677641, compoundYield 31%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 1140TolueneSolvent

Procedure

After adding a solution of 2-(4-fluorophenyl)acetyl isothiocyanate in toluene (0.25 M, 2.5 ml) to a solution of 4-(4-amino-2-fluorophenoxy)-6-{[4-(1-methylpiperidin-4-yl)piperazin-1-yl]carbonylamino}pyrimidine (134 mg) and (+)-10-camphorsulfonic acid (109 mg) in ethanol (3.0 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 in that order and dried over anhydrous sodium sulfate. The solvent was distilled off, and the residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate, then ethyl acetate:methanol=98:2). Fractions containing the target compound were concentrated to provide the title compound (60.7 mg, 31%) 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 in that order
  3. dry with materialdried over anhydrous sodium sulfate
  4. distillationThe solvent was distilled off
  5. customthe residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent
  6. additionFractions containing the target compound
  7. concentrationwere concentrated

Sources & evidence

ORD record
ord-0ebfbe3fb0604c6ab6bdfb00ce847a15
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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