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

HRID 1275339Notes

Reaction equation

HRID 1275339 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.C1[C@H]2[C@@H](CCCC2)CCC1.[H-].[Na+].Cl[P:38]([C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1.[I-].[Na+].S(=O)(O)[O-:54].[Na+]>C(OCC)(=O)C>[C:39]1([P:38]([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:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)=[O:54])[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1

Participants

8

Reactant 6

HCID 5238Sodium IodideHCID 24758Sodium hydrideHCID 66180ChlorodiphenylphosphineHCID 9819937N-(4-(4-fluorophenyl)-5-(hydroxymethyl)-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamideHCID 23665763Sodium BisulfiteHCID 178420442HCID 178420442, compound

Product 1

HCID 9937035N-(5-((diphenylphosphoryl)methyl)-4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl)-N-methylmethanesulfonamide

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

1.00 g (2.83 mmol) of [4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methylsulfonylamino)pyrimidin-5-yl]methanol was initially charged in 5 ml of cis/trans-decalin and admixed with 204 mg (4.68 mmol) of sodium hydride (55 percent dispersion in mineral oil). After 30 min at room temperature, 680 mg (2.93 mmol) of chlorodiphenylphosphine was added with vigorous stirring over a period of 6 min. The mixture was admixed with 52.2 mg (0.35 mmol) of sodium iodide and heated at 184° to 186° C. for 2 h, 15 min. After cooling to room temperature, 50 ml of 38 to 40 percent strength sodium bisulfite solution and 50 ml of ethyl acetate were added. The organic phase was separated off and the aqueous phase was extracted with 50 ml of ethyl acetate. The combined organic phases were dried over magnesium sulfate and concentrated under reduced pressure. This gave 1.74 g of crude product which was purified by silica gel chromatography (mobile phase: n-hexane/ethyl acetate 1:2). This gave 382.4 mg (25.1 percent) of N-[5-(diphenylphosphinoylmethyl)-4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl]-N-methylmethanesulfonamide in the form of a colorless solid. The melting point was 180° to 185° C. Other data concerning the product was:

Workup

  1. temperatureheated at 184° to 186° C. for 2 h, 15 min
  2. customThe organic phase was separated off
  3. extractionthe aqueous phase was extracted with 50 ml of ethyl acetate
  4. dry with materialThe combined organic phases were dried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThis gave 1.74 g of crude product which was purified by silica gel chromatography (mobile phase: n-hexane/ethyl acetate 1:2)

Sources & evidence

ORD record
ord-38942fba21d6435090682c1d4d5f561a
Source dataset
uspto-grants-2000_12
Patent number
US06160115

Reaction notes

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