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

HRID 1275340Notes

Reaction equation

HRID 1275340 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.[H-].[Na+].Cl[P:28]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.[OH2:41]>C1(C)C(C)=CC=CC=1>[C:29]1([P:28]([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:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)=[O:41])[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 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 53.5%

Reagents, catalysts & solvents 1

HCID 7237O-XyleneSolvent2×

Conditions

Temperature
135 °C

Procedure

282.8 mg (0.80 mmol) of [4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methylsulphonylamino)pyrimidin-5-yl]methanol was initially charged in 4.5 ml of xylene (isomer mixture) and admixed with 55 mg (1.30 mmol) of sodium hydride (55 percent dispersion in mineral oil). After 35 min, 185 mg (0.84 mmol) of chlorodiphenylphosphine in 1.5 ml of xylene was added at room temperature with vigorous stirring over a period of 5 min, and the mixture was subsequently heated at 135° C. for 20 h. After cooling to room temperature, the mixture was admixed with 15 ml of water and extracted with 10 ml of ethyl acetate. The organic phase was separated off and the aqueous phase was extracted with 2×10 ml of ethyl acetate. The combined organic phases were subsequently dried (MgSO4) and concentrated under reduced pressure. This gave 510 mg of crude product which was purified by silica gel chromatography (mobile phase: n-hexane/ethyl acetate 1:2, then ethyl acetate), and 230 mg (53.5 percent) of N-[5-(diphenylphosphinoylmethyl)-4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl]-N-methylmethanesulphonamide was isolated in the form of a colorless solid.

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionextracted with 10 ml of ethyl acetate
  3. customThe organic phase was separated off
  4. extractionthe aqueous phase was extracted with 2×10 ml of ethyl acetate
  5. dry with materialThe combined organic phases were subsequently dried (MgSO4)
  6. concentrationconcentrated under reduced pressure
  7. customThis gave 510 mg of crude product which was purified by silica gel chromatography (mobile phase

Sources & evidence

ORD record
ord-d1aaf4bdcd114401878bf85b473f5a3c
Source dataset
uspto-grants-2000_12
Patent number
US06160115

Reaction notes

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