Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → Cyclopropyl-(5-[(2,6-difluoro-3,5-dimethoxy-phenylimino)-methyl]-2-methylsulfanyl-pyrimidin-4-yl)-amine

HRID 459951Notes

Reaction equation

HRID 459951 reaction equation
[CH:1]1([NH:4][C:5]2[C:10]([CH:11]=O)=[CH:9][N:8]=[C:7]([S:13][CH3:14])[N:6]=2)[CH2:3][CH2:2]1.[F:15][C:16]1[C:21]([O:22][CH3:23])=[CH:20][C:19]([O:24][CH3:25])=[C:18]([F:26])[C:17]=1[NH2:27].C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>C1(C)C=CC=CC=1>[CH:1]1([NH:4][C:5]2[C:10]([CH:11]=[N:27][C:17]3[C:18]([F:26])=[C:19]([O:24][CH3:25])[CH:20]=[C:21]([O:22][CH3:23])[C:16]=3[F:15])=[CH:9][N:8]=[C:7]([S:13][CH3:14])[N:6]=2)[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 102618922,6-Difluoro-3,5-dimethoxybenzenamineHCID 105363904-Cyclopropylamino-2-methylsulfanyl-pyrimidine-5-carbaldehyde

Product 1

HCID 18444840Cyclopropyl-(5-[(2,6-difluoro-3,5-dimethoxy-phenylimino)-methyl]-2-methylsulfanyl-pyrimidin-4-yl)-amineYield 70%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of the 7.00 g (33.4 mmol) of 4-cyclopropylamino-2-methylsulfanyl-pyrimidine-5-carbaldehyde in 500 mL of toluene was added 6.33 g 33.4 mmol, 1 equivalent) of 2,6-difluoro-3,5-dimethoxy-phenylamine and 1.94 g (8.36 mmol, 0.25 equivalents) of camphorsulfonic acid. The reaction was warmed to reflux and the formed water was removed with the aid of a Dean-Stark trap. After reacting for 48 hours, the reaction was concentrated in vacuo. The residue was stirred with ether and filtered. The filter pad was dissolved in dichloromethane, stirred with silica gel, and concentrated in vacuo. The residue was placed in the sample injection module of a Biotage FLASH 75 chromatographic apparatus. Chromatography of the crude material down a Biotage 500 g silica gel column with 2:1 hexane/ethyl acetate, then 1:1 hexane/ethyl acetate and finally 9:1 ethyl acetate/ethanol gave 8.92 g (70%) of title compound as a solid: mp 172° C.–174° C. MS (APCI) (m+1)/z 381.0 Analysis calculated for C17H18aF2N4SO2: C, 53.67; H, 4.77; N, 14.73. Found: C, 53.54; H, 4.58; N, 14.61.

Workup

  1. temperatureThe reaction was warmed
  2. temperatureto reflux
  3. customthe formed water was removed with the aid of a Dean-Stark trap
  4. concentrationthe reaction was concentrated in vacuo
  5. filtrationfiltered
  6. dissolutionThe filter pad was dissolved in dichloromethane
  7. stirringstirred with silica gel
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-9d23282837ae4874bce6c0eb3ce3809d
Source dataset
uspto-grants-2007_03
Patent number
US07196090B2

Reaction notes

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