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

HRID 1275344Notes

Reaction equation

HRID 1275344 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+].O>C1(C)C=CC=CC=1.[Cl-].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

7

Reactant 4

HCID 962WaterHCID 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-methylmethanesulfonamide

Reagents, catalysts & solvents 2

HCID 70681Tetrabutylammonium ChlorideCatalystHCID 1140TolueneSolvent2×

Conditions

Temperature
111 °C

Procedure

2.03 g (5.69 mmol) of [4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methylsulfonylamino)pyrimidin-5-yl]methanol was initially charged in 13 g of toluene and, with ice-bath cooling, admixed with 1.67 g (7.51 mmol) of chlorodiphenylphosphine in 2 g of toluene. The mixture was heated at 111° C. for 2.5 h. After cooling to room temperature, 1.08 g (8.66 mmol) of a 45 percent strength potassium hydroxide solution and 175 mg (0.574 mmol) of tetrabutylammonium chloride was added, and the mixture was stirred vigorously at 60° C. for 2 h. 30 ml of water was added to the warm reaction mixture. The mixture was briefly stirred at 60° C. and slowly cooled to 4° C., and the precipitated solid was filtered off. The product was washed with cold water (10 ml) and cold toluene (10 ml) and dried under reduced pressure at 40° C. 2.66 g (84.1 percent; content: 96.6 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. temperatureAfter cooling to room temperature
  2. stirringThe mixture was briefly stirred at 60° C.
  3. temperatureslowly cooled to 4° C.
  4. filtrationthe precipitated solid was filtered off
  5. washThe product was washed with cold water (10 ml) and cold toluene (10 ml)
  6. customdried under reduced pressure at 40° C

Sources & evidence

ORD record
ord-105b3e0ae3854a9991ce347de6db11b1
Source dataset
uspto-grants-2000_12
Patent number
US06160115

Reaction notes

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