Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → HCID 59011634, compound

HRID 492858Notes

Reaction equation

HRID 492858 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:39]=[CH:38][C:18]([O:19][C:20]2[N:25]=[CH:24][N:23]=[C:22]([NH:26][C:27](=[O:37])[N:28]([CH3:36])[CH:29]3[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]3)[CH:21]=2)=[CH:17][C:16]=1[F:40].C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>C1(C)C=CC=CC=1.C(O)C>[F:40][C:16]1[CH:17]=[C:18]([CH:38]=[CH:39][C:15]=1[NH:14][C:12]([NH:11][C:9](=[O:10])[CH2:8][C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=1)=[S:13])[O:19][C:20]1[N:25]=[CH:24][N:23]=[C:22]([NH:26][C:27](=[O:37])[N:28]([CH3:36])[CH:29]2[CH2:30][CH2:31][N:32]([CH3:35])[CH2:33][CH2:34]2)[CH:21]=1

Participants

6

Reactant 3

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 231532482-(4-Fluorophenyl)acetyl isothiocyanateHCID 23153632HCID 23153632, compound

Product 1

HCID 59011634HCID 59011634, compoundYield 10%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 1140TolueneSolvent

Procedure

After adding a solution of 2-(4-fluorophenyl)acetyl isothiocyanate in toluene (0.2 M, 3.4 ml) to a solution of crude 3-[6-(4-amino-3-fluorophenoxy)pyrimidin-4-yl]-1-methyl-1-(1-methylpiperidin-4-yl)urea and (+)-10-camphorsulfonic acid (86.2 mg) in ethanol (2.5 ml) at room temperature, the mixture was stirred for 4 hours. The reaction mixture was then 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). Fractions containing the target compound were concentrated under reduced pressure, and diethyl ether (2.0 ml) was added to the resultant residue to precipitate crystals. The crystals were filtered and then subjected to aeration drying to provide the title compound (21.0 mg, 10%) as white crystals.

Workup

  1. customThe reaction mixture was then 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; ethyl acetate)
  6. additionFractions containing the target compound
  7. concentrationwere concentrated under reduced pressure, and diethyl ether (2.0 ml)
  8. additionwas added to the resultant residue
  9. customto precipitate crystals
  10. filtrationThe crystals were filtered
  11. customdrying

Sources & evidence

ORD record
ord-dddde52ef39346909113b639faa69471
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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