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

HRID 1275341Notes

Reaction equation

HRID 1275341 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.[I-].[Na+].S(=O)(O)[O-:44].[Na+]>C1(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:44])[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

7

Reactant 5

HCID 5238Sodium Iodide2×HCID 24758Sodium hydrideHCID 66180ChlorodiphenylphosphineHCID 9819937N-(4-(4-fluorophenyl)-5-(hydroxymethyl)-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamideHCID 23665763Sodium Bisulfite

Product 1

HCID 9937035N-(5-((diphenylphosphoryl)methyl)-4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamideYield 27.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
108 °C

Procedure

512 mg (1.45 mmol) of [4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methylsulfonylamino)pyrimidin-5-yl]methanol was initially charged in 8 ml of toluene and admixed with 96 mg (2.20 mmol) of sodium hydride (55 percent dispersion in mineral oil). After 1 h, 333.5 mg (1.44 mmol) of chlorodiphenylphosphine in 2.5 ml of toluene was added at room temperature with vigorous stirring over a period of 5 min. The mixture was admixed with 28.7 mg (0.19 mmol) of sodium iodide and heated at 108° C. for 22 h. After 6 h, a further 28.7 mg (0.19 mmol) of sodium iodide were added. After cooling to room temperature, the mixture was admixed with 30 ml of 38 to 40percent strength sodium bisulfite solution and extracted with 50 ml of ethyl acetate. The organic phase was separated off and the aqueous phase was extracted with 50 ml of ethyl acetate. The combined organic phases were subsequently concentrated under reduced pressure. This gave 740 mg of crude product which was purified by silica gel chromatography (mobile phase:ethyl acetate), and 212.7 mg (27.3 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. waitAfter 6 h
  2. temperatureAfter cooling to room temperature
  3. extractionextracted with 50 ml of ethyl acetate
  4. customThe organic phase was separated off
  5. extractionthe aqueous phase was extracted with 50 ml of ethyl acetate
  6. concentrationThe combined organic phases were subsequently concentrated under reduced pressure
  7. customThis gave 740 mg of crude product which was purified by silica gel chromatography (mobile phase:ethyl acetate)

Sources & evidence

ORD record
ord-01137dba3f46413884850de944ecdff1
Source dataset
uspto-grants-2000_12
Patent number
US06160115

Reaction notes

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