Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → HCID 57677702, compound

HRID 492845Notes

Reaction equation

HRID 492845 reaction equation
[NH2:1][C:2]1[CH:27]=[CH:26][C:5]([O:6][C:7]2[N:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]([N:16]3[CH2:21][CH2:20][CH:19]([N:22]4[CH2:25][CH2:24][CH2:23]4)[CH2:18][CH2:17]3)=[O:15])[CH:8]=2)=[C:4]([F:28])[CH:3]=1.CC1(C)C2(CS(O)(=O)=O)C(CC1CC2)=O.[C:44]1([CH2:50][C:51]([N:53]=[C:54]=[S:55])=[O:52])[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1.C(=O)([O-])O.[Na+]>C(O)C.C(OCC)(=O)C.C(#N)C>[F:28][C:4]1[CH:3]=[C:2]([NH:1][C:54]([NH:53][C:51](=[O:52])[CH2:50][C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=2)=[S:55])[CH:27]=[CH:26][C:5]=1[O:6][C:7]1[N:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]([N:16]2[CH2:21][CH2:20][CH:19]([N:22]3[CH2:25][CH2:24][CH2:23]3)[CH2:18][CH2:17]2)=[O:15])[CH:8]=1

Participants

8

Reactant 4

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 516892Sodium BicarbonateHCID 12454157Phenylacetyl isothiocyanateHCID 57677632HCID 57677632, compound

Product 1

HCID 57677702HCID 57677702, compoundYield 61.8%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

After dissolving 4-(azetidin-1-yl)piperidine-1-carboxylic acid [6-(4-amino-2-fluorophenoxy)pyrimidin-4-yl]amide (40 mg) in ethanol (1 ml) under a nitrogen atmosphere, D-10-camphorsulfonic acid (22.3 mg) was added and the mixture was stirred for 5 minutes. Phenylacetyl isothiocyanate (34.1 mg)-acetonitrile (0.5 ml×3) was added thereto, and the mixture was stirred for 30 minutes. Ethyl acetate (30 ml) and saturated aqueous sodium hydrogencarbonate (20 ml) were added to the reaction mixture for partition, and the organic layer was washed with saturated aqueous sodium hydrogencarbonate (20 ml), water (20 ml) and brine (20 ml) and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate) and then fractions containing the target compound were concentrated under reduced pressure. Diethyl ether (1.5 ml) and hexane (1.5 ml) were added to the resultant residue to produce a suspension. After filtering the solid, it was subjected to aeration drying to provide the title compound (33.5 mg, 61.8%) as white powder.

Workup

  1. stirringthe mixture was stirred for 30 minutes
  2. customfor partition
  3. washthe organic layer was washed with saturated aqueous sodium hydrogencarbonate (20 ml), water (20 ml) and brine (20 ml)
  4. dry with materialdried over anhydrous sodium sulfate
  5. distillationThe solvent was distilled off under reduced pressure
  6. customThe resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate)
  7. additionfractions containing the target compound
  8. concentrationwere concentrated under reduced pressure
  9. additionDiethyl ether (1.5 ml) and hexane (1.5 ml) were added to the resultant residue
  10. customto produce a suspension
  11. filtrationAfter filtering the solid, it
  12. customdrying

Sources & evidence

ORD record
ord-023323f58292403784a933c803296d47
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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