Sodium hydride → 4-Chloro-6-(2,6-difluoro-phenylamino)-2-methylsulfanyl-pyrimidine-5-carbonitrile

HRID 644779Notes

Reaction equation

HRID 644779 reaction equation
[F:1][C:2]1[CH:8]=[CH:7][CH:6]=[C:5]([F:9])[C:3]=1[NH2:4].[H-].[Na+].[Cl:12][C:13]1[C:18]([C:19]#[N:20])=[C:17](Cl)[N:16]=[C:15]([S:22][CH3:23])[N:14]=1>CS(C)=O.CCOC(C)=O>[Cl:12][C:13]1[C:18]([C:19]#[N:20])=[C:17]([NH:4][C:3]2[C:2]([F:1])=[CH:8][CH:7]=[CH:6][C:5]=2[F:9])[N:16]=[C:15]([S:22][CH3:23])[N:14]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 796472,6-DifluoroanilineHCID 42016204,6-Dichloro-2-(methylsulfanyl)pyrimidine-5-carbonitrile

Product 1

HCID 211144724-Chloro-6-(2,6-difluoro-phenylamino)-2-methylsulfanyl-pyrimidine-5-carbonitrileYield 87%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

2,6-di-Fluoroaniline (2.66 mL, 24 mmol), DMSO (12 mL) and NaH (0.912 g, 22.8 mmol) were combined at 23°. When the foaming ceased 4,6-Dichloro-2-methylsulfanyl-pyrimidine-5-carbonitrile [Santilli, et al., J. Heterocycl. Chem. 1971, 8, 445-453] (5.0 g, 22.82 mmol) was added in DMSO (12 mL). The reaction exothermed and the temperature was moderated with cold H2O bath, then stirred at 23° for 3 h. The reaction was diluted with EtOAc (300 mL) and washed with H2O (4×) and satd aq NaCl (1×). Dried (Na2SO4) and concentrated to afford 6.21 g (82%) of a tan foam. LC MS m/z=313 (MH+), Rt=2.37 min.

Workup

  1. customwere combined at 23°
  2. customThe reaction exothermed and the temperature was moderated with cold H2O bath
  3. washwashed with H2O (4×)
  4. dry with materialDried (Na2SO4)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-d2c8cdebd00f4ca4997ef5cbe62ac2fb
Source dataset
uspto-grants-2010_04
Patent number
US07700768B2

Reaction notes

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