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

HRID 1275342Notes

Reaction equation

HRID 1275342 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(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 41.3%

Reagents, catalysts & solvents 1

HCID 7237O-XyleneSolvent2×

Conditions

Temperature
136 °C

Procedure

502.6 mg (1.42 mmol) of [4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methylsulfonylamino)pyrimidin-5-yl]methanol was initially charged in 8 ml of xylene (isomer mixture) and admixed with 96.6 mg (2.21 mmol) of sodium hydride (55 percent dispersion in mineral oil). After 1 hour, 340.8 mg (1.47 mmol) of chlorodiphenylphosphine in 2.5 ml of xylene was added at room temperature with vigorous stirring over a period of 5 min. The mixture was admixed with 34.6 mg (0.23 mmol) of sodium iodide and heated at 136° C. for 19 h. After 3 h, a further 25.1 mg of sodium iodide were added. After cooling to room temperature, the mixture was admixed with 30 ml of dilute 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 906 mg of crude product which was purified by silica gel chromatography (mobile phase: ethyl acetate), and 315.9 mg (41.3 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 3 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 906 mg of crude product which was purified by silica gel chromatography (mobile phase: ethyl acetate)

Sources & evidence

ORD record
ord-7bd5940e1fbc4deca06a47e672ff82ed
Source dataset
uspto-grants-2000_12
Patent number
US06160115

Reaction notes

Loading…