Sodium hydride → 2-chloro-N-(2-(isopropylsulfonyl)phenyl)-5-methylpyrimidin-4-amine

HRID 921301Notes

Reaction equation

HRID 921301 reaction equation
[H-].[Na+].[NH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[S:10]([CH:13]([CH3:15])[CH3:14])(=[O:12])=[O:11].[Cl:16][C:17]1[N:22]=[C:21](Cl)[C:20]([CH3:24])=[CH:19][N:18]=1>CN(C=O)C>[Cl:16][C:17]1[N:22]=[C:21]([NH:3][C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=2[S:10]([CH:13]([CH3:15])[CH3:14])(=[O:12])=[O:11])[C:20]([CH3:24])=[CH:19][N:18]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 74508Pyrimidine, 2,4-dichloro-5-methyl-HCID 126463662-(Propane-2-sulfonyl)aniline

Product 1

HCID 597644732-chloro-N-(2-(isopropylsulfonyl)phenyl)-5-methylpyrimidin-4-amineYield 24%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a suspension of NaH (60% dispersion in mineral oil, 40.0 mg, 1.00 mmol) in 2 mL of DMF at room temperature was added 1-amino-2-(isopropylsulphonyl)benzene (0.20 g, 1.0 mmol) as a solid in 3 portions. After 30 minutes of stirring at room temperature, 2,4-dichloro-5-methylpyrimidine (0.17 g, 1.0 mmol) was added as a solution in 1 mL DMF. The reaction mixture stirred for 3 h at room temperature. The reaction was quenched with saturated sodium bicarbonate solution and the solution extracted ethyl acetate. The organic layers were combined, washed with saturated sodium chloride solution, dried with sodium sulfate, filtered and concentrated. The crude residue was purified by silica gel chromatography (0-30% ethyl acetate:heptane) to afford the desired compound as an off-white solid (78 mg, 24% yield). MS/ES+: m/z=326.

Workup

  1. stirringThe reaction mixture stirred for 3 h at room temperature
  2. customThe reaction was quenched with saturated sodium bicarbonate solution
  3. extractionthe solution extracted ethyl acetate
  4. washwashed with saturated sodium chloride solution
  5. dry with materialdried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude residue was purified by silica gel chromatography (0-30% ethyl acetate:heptane)

Sources & evidence

ORD record
ord-72be86bb321e487f8d1eef1d83be8572
Source dataset
uspto-grants-2016_03
Patent number
US09273077B2

Reaction notes

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