Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → HCID 57677610, compound

HRID 492906Notes

Reaction equation

HRID 492906 reaction equation
[NH2:1][C:2]1[CH:30]=[CH:29][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][N:19]([CH2:22][CH2:23][N:24]4[CH2:28][CH2:27][CH2:26][CH2:25]4)[CH2:18][CH2:17]3)=[O:15])[CH:8]=2)=[C:4]([F:31])[CH:3]=1.CC1(C)C2(CS(O)(=O)=O)C(CC1CC2)=O.[C:47]1([CH2:53][C:54]([N:56]=[C:57]=[S:58])=[O:55])[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1>C(O)C.C1(C)C=CC=CC=1>[F:31][C:4]1[CH:3]=[C:2]([NH:1][C:57]([NH:56][C:54](=[O:55])[CH2:53][C:47]2[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=2)=[S:58])[CH:30]=[CH:29][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][N:19]([CH2:22][CH2:23][N:24]3[CH2:28][CH2:27][CH2:26][CH2:25]3)[CH2:18][CH2:17]2)=[O:15])[CH:8]=1

Participants

6

Reactant 3

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 12454157Phenylacetyl isothiocyanateHCID 57677757HCID 57677757, compound

Product 1

HCID 57677610HCID 57677610, compoundYield 8.4%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 1140TolueneSolvent

Procedure

After dissolving 4-[2-(pyrrolidin-1-yl)ethyl]piperazine-1-carboxylic acid [6-(4-amino-2-fluorophenoxy)pyrimidin-4-yl]amide (49 mg) in ethanol (2 ml) under a nitrogen atmosphere, D-10-camphorsulfonic acid (53 mg) was added and the mixture was stirred for 5 minutes. A 0.25 M solution of 2-phenylacetyl isothiocyanate in toluene (0.684 ml) was added to the reaction mixture and stirring was carried out for 1 hour. The reaction mixture was partitioned between ethyl acetate (50 ml) and saturated aqueous sodium hydrogencarbonate (30 ml). The organic layer was washed with saturated aqueous sodium hydrogencarbonate (30 ml), water (30 ml) and brine (30 ml) in that order and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and then the resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; heptane:ethyl acetate=1:8). Fractions containing the target compound were concentrated under reduced pressure, and then diethyl ether (1.0 ml) and hexane (1.5 ml) were added to the resultant residue to produce a suspension of the solid. After filtering the solid, it was subjected to aeration drying to provide the title compound (5.8 mg, 8.4%) as white powder.

Workup

  1. stirringstirring
  2. waitwas carried out for 1 hour
  3. customThe reaction mixture was partitioned between ethyl acetate (50 ml) and saturated aqueous sodium hydrogencarbonate (30 ml)
  4. washThe organic layer was washed with saturated aqueous sodium hydrogencarbonate (30 ml), water (30 ml) and brine (30 ml) in that order
  5. dry with materialdried over anhydrous sodium sulfate
  6. distillationThe solvent was distilled off under reduced pressure
  7. customthe resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; heptane:ethyl acetate=1:8)
  8. additionFractions containing the target compound
  9. concentrationwere concentrated under reduced pressure
  10. additiondiethyl ether (1.0 ml) and hexane (1.5 ml) were added to the resultant residue
  11. customto produce
  12. additiona suspension of the solid
  13. filtrationAfter filtering the solid, it
  14. customdrying

Sources & evidence

ORD record
ord-7e5a61277e0b43cb81f71f58cc099dae
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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