Sodium hydride → (E)-N,N-Dipropyl-4-[(4-amino-6-chloro-2-pyrimidinyl)thio]-2-butenamide

HRID 1637720Notes

Reaction equation

HRID 1637720 reaction equation
S(O)(=O)(=O)C.[NH2:6][C:7]1[CH:12]=[C:11]([Cl:13])[N:10]=[C:9]([SH:14])[N:8]=1.[H-].[Na+].Cl[CH2:18]/[CH:19]=[CH:20]/[C:21]([N:23]([CH2:27][CH2:28][CH3:29])[CH2:24][CH2:25][CH3:26])=[O:22]>CN(C=O)C>[CH2:27]([N:23]([CH2:24][CH2:25][CH3:26])[C:21](=[O:22])/[CH:20]=[CH:19]/[CH2:18][S:14][C:9]1[N:8]=[C:7]([NH2:6])[CH:12]=[C:11]([Cl:13])[N:10]=1)[CH2:28][CH3:29]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 187998284-chloro-N,N-dipropylcrotonamideHCID 178505342HCID 178505342, compound

Product 1

HCID 6476885(E)-N,N-Dipropyl-4-[(4-amino-6-chloro-2-pyrimidinyl)thio]-2-butenamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-Chlorocrotonyl chloride (1.02 g, 7.35 mmol) in ether (10 ml) is combined with dipropylamine (1.64 g, 16.17 mmol) in ether (5 ml) at -15° C. in a flame dried flask. The reaction is warmed to ambient temperature, stirred for 1 to 2 hours, quenched with water (30 ml), extracted with ethyl acetate (2×30 ml), washed with saline (30 ml), dried over sodium sulfate, concentrated in vacuo, and chromatographed on silica gel (230-400 mesh, 100 ml), eluting with hexane/ethyl acetate (60/40). The appropriate fractions are combined (Rf =0.53, TLC, hexane/ethyl acetate, 25/75) and concentrated in vacuo to give 4-chloro-N,N-dipropylcrotonamide. 4-Amino-6-chloro-2-mercaptopyrimidine mesylate (0.30 g, 1.16 mmol) is dissolved in DMF (5 ml) and sodium hydride (0.06 g, 2.55 mmol) at ambient temperature followed by the addition of 4-chloro-N,N-dipropylcrotonamide (0.23 g, 1.13 mmol). The reaction is stirred for 2 to 15 hours, quenched with excess water, extracted with ethyl acetate (3×20 ml). The extracts are combined, washed with saline (20 ml), dried over sodium sulfate, concentrated in vacuo and chromatographed on silica gel (230-400 mesh, 100 ml), eluting with hexane/ethyl acetate (60/40). The appropriate fractions are combined (Rf =0.40, TLC, hexane/ethyl acetate, 25/75) and concentrated in vacuo to give the title compound, mp 139-142° C.

Workup

  1. customquenched with excess water
  2. extractionextracted with ethyl acetate (3×20 ml)
  3. washwashed with saline (20 ml)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customchromatographed on silica gel (230-400 mesh, 100 ml)
  7. washeluting with hexane/ethyl acetate (60/40)
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-74b50972ecff42deb6c943ea5b2aa914
Source dataset
uspto-grants-2000_03
Patent number
US06043248

Reaction notes

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