Potassium Hydroxide → N-(5-((diphenylphosphoryl)methyl)-4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamide

HRID 1275343Notes

Reaction equation

HRID 1275343 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([CH2:14]O)=[C:12]([CH:16]([CH3:18])[CH3:17])[N:11]=[C:10]([N:19]([CH3:24])[S:20]([CH3:23])(=[O:22])=[O:21])[N:9]=2)=[CH:4][CH:3]=1.Cl[P:26]([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.[OH-:39].[K+]>C1(C)C=CC=CC=1.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[C:27]1([P:26]([CH2:14][C:13]2[C:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)=[N:9][C:10]([N:19]([CH3:24])[S:20]([CH3:23])(=[O:22])=[O:21])=[N:11][C:12]=2[CH:16]([CH3:18])[CH3:17])([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[O:39])[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 66180ChlorodiphenylphosphineHCID 9819937N-(4-(4-fluorophenyl)-5-(hydroxymethyl)-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamide

Product 1

HCID 9937035N-(5-((diphenylphosphoryl)methyl)-4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamideYield 65.6%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 1140TolueneSolvent

Conditions

Temperature
108 °C

Procedure

With ice-bath cooling, 1.05 g (2.95 mmol) of [4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methylsulfonylamino)pyrimidin-5-yl]methanol was initially charged in 7 g of toluene and admixed with stirring with 820 mg (3.69 mmol) of chlorodiphenylphosphine. The mixture was heated at 108° C. for 3 h. After cooling to room temperature, 553 mg (4.43 mmol) of aqueous potassium hydroxide solution (45 percent strength) and 97.5 mg (0.29 mmol) of tetrabutylammonium bromide was added, and the mixture was stirred vigorously at 60° C. for 1 h. The heat source was removed and the reaction mixture, which was still warm, was admixed with 20 ml of water. The mixture was slowly cooled to 4° C., and the precipitated solid was filtered off. The product was washed with cold water and toluene and dried under reduced pressure at 40° C. 1.04 g (64.1 percent; content: 97.6 percent) of N-[5-(diphenylphosphinoylmethyl)-4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl]-N-methylmethanesulfonamide was isolated in the form of a colorless solid.

Workup

  1. temperatureWith ice-bath cooling
  2. temperatureAfter cooling to room temperature
  3. customThe heat source was removed
  4. temperaturethe reaction mixture, which was still warm
  5. temperatureThe mixture was slowly cooled to 4° C.
  6. filtrationthe precipitated solid was filtered off
  7. washThe product was washed with cold water and toluene
  8. customdried under reduced pressure at 40° C

Sources & evidence

ORD record
ord-7ae4343ffaee443bbfba398676b5d535
Source dataset
uspto-grants-2000_12
Patent number
US06160115

Reaction notes

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