Sodium hydride → N-(2,6-dichloro-5-fluoro-pyrimidin-4-yl)-N-methyl-methanesulfonamide

HRID 415432Notes

Reaction equation

HRID 415432 reaction equation
[H-].[Na+].[CH3:3][NH:4][S:5]([CH3:8])(=[O:7])=[O:6].[Cl:9][C:10]1[N:15]=[C:14]([Cl:16])[C:13]([F:17])=[C:12](Cl)[N:11]=1>CN(C=O)C.C1COCC1>[Cl:9][C:10]1[N:11]=[C:12]([N:4]([CH3:3])[S:5]([CH3:8])(=[O:7])=[O:6])[C:13]([F:17])=[C:14]([Cl:16])[N:15]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 97632N-MethylmethanesulfonamideHCID 133889932,4,6-Trichloro-5-fluoropyrimidine

Product 1

HCID 86624844N-(2,6-dichloro-5-fluoro-pyrimidin-4-yl)-N-methyl-methanesulfonamideYield 64%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of NaH (60% in mineral oil, 176 mg, 8.58 mmol) in anhydrous DMF (2 mL), N-methylmethanesulfonamide (436 mg, 4.0 mmol) in DMF (2 ml) was added. This reaction mixture was stirred for 30 min at room temperature and then added dropwise to the solution of 2,4,6-trichloro-5-fluoropyrimidine (804 mg, 4.0 mmol) in THF (30 ml) at 0° C. The reaction mixture was stirred from 0° C. to room temperature overnight. The solvent was evaporated and the residue was purified by silica gel chromatography (by ISCO Combiflash with gradient 0-30% ethyl acetate in Hexane with 1% TEA. A white solid (700 mg) was obtained, yield 64%. NMR (400 MHz, DMSO) 83.38 (s, 3H), 3.31 (s, 3H).

Workup

  1. stirringThe reaction mixture was stirred from 0° C. to room temperature overnight
  2. customThe solvent was evaporated
  3. customthe residue was purified by silica gel chromatography (by ISCO Combiflash with gradient 0-30% ethyl acetate in Hexane with 1% TEA

Sources & evidence

ORD record
ord-9715fa285112424ea9b64663547d55bc
Source dataset
uspto-grants-2012_01
Patent number
US08088784B2

Reaction notes

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