Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → HCID 57677542, compound

HRID 492853Notes

Reaction equation

HRID 492853 reaction equation
[NH2:1][C:2]1[CH:26]=[CH:25][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]([CH3:24])[CH3:23])[CH2:18][CH2:17]3)=[O:15])[CH:8]=2)=[C:4]([F:27])[CH:3]=1.CC1(C)C2(CS(O)(=O)=O)C(CC1CC2)=O.[F:43][C:44]1[CH:49]=[CH:48][C:47]([CH2:50][C:51]([N:53]=[C:54]=[S:55])=[O:52])=[CH:46][CH:45]=1.C(=O)([O-])O.[Na+]>C(O)C.C1(C)C=CC=CC=1.C(OCC)(=O)C>[F:27][C:4]1[CH:3]=[C:2]([NH:1][C:54]([NH:53][C:51](=[O:52])[CH2:50][C:47]2[CH:48]=[CH:49][C:44]([F:43])=[CH:45][CH:46]=2)=[S:55])[CH:26]=[CH:25][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]([CH3:23])[CH3:24])[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 231532482-(4-Fluorophenyl)acetyl isothiocyanate2×HCID 57677646HCID 57677646, compound

Product 1

HCID 57677542HCID 57677542, compoundYield 18.4%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 1140TolueneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

After dissolving 4-dimethylaminopiperidine-1-carboxylic acid [6-(4-amino-2-fluorophenoxy)pyrimidin-4-yl]amide (89.3 mg) in ethanol (2 ml), D-10-camphorsulfonic acid (55.3 mg) was added and the mixture was stirred for 5 minutes under a nitrogen atmosphere. A 0.24 M solution of 2-(4-fluorophenyl)acetyl isothiocyanate in toluene (0.4 ml) was then added and the mixture was stirred for 1 hour. Then, a 0.24 M solution of 2-(4-fluorophenyl)acetyl isothiocyanate in toluene (0.4 ml) was further added to the reaction mixture and stirring was continued for 1 hour. 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; heptane:ethyl acetate=8:1), and then fractions containing the target compound were concentrated under reduced pressure. Diethyl ether (0.5 ml) and hexane (4.0 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 (24.9 mg, 18.4%) as a white solid.

Workup

  1. additionwas added
  2. stirringthe mixture was stirred for 1 hour
  3. stirringstirring
  4. waitwas continued for 1 hour
  5. customfor partition
  6. washthe organic layer was washed with saturated aqueous sodium hydrogencarbonate (20 ml), water (20 ml) and brine (20 ml)
  7. dry with materialdried over anhydrous sodium sulfate
  8. distillationThe solvent was distilled off under reduced pressure
  9. customThe resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; heptane:ethyl acetate=8:1)
  10. additionfractions containing the target compound
  11. concentrationwere concentrated under reduced pressure
  12. additionDiethyl ether (0.5 ml) and hexane (4.0 ml) were added to the resultant residue
  13. customto produce a suspension
  14. filtrationAfter filtering the solid, it
  15. customdrying

Sources & evidence

ORD record
ord-6a76d0e356064a91a8d956b2708251b7
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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