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

HRID 1637724Notes

Reaction equation

HRID 1637724 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[CH:18]([CH3:28])/[CH:19]=[CH:20]/[C:21]([N:23]([CH2:26][CH3:27])[CH2:24][CH3:25])=[O:22]>CN(C=O)C>[CH2:26]([N:23]([CH2:24][CH3:25])[C:21](=[O:22])/[CH:20]=[CH:19]/[CH:18]([S:14][C:9]1[N:8]=[C:7]([NH2:6])[CH:12]=[C:11]([Cl:13])[N:10]=1)[CH3:28])[CH3:27]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 18799937(E)-4-chloro-N,N-diethyl-2-pentenamideHCID 178505342HCID 178505342, compound

Product 1

HCID 6476887(E)-N,N-Diethyl-4-[(4-amino-6-chloro-2-pyrimidinyl)thio]-2-pentenamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To (E)-N,N-Diethyl-4-hydroxy-2-pentenamide (0.67 g, 3.93 mmol) in methylene chloride cooled to -15° C. in a flame dried flask is added dichlorotriphenylphosphorane (1.40 g, 4.33 mmol). The reaction is warmed to ambient temperature, quenched by addition of ice (10 ml), extracted with methylene chloride (3×20 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 (75/25). The appropriate fractions are combined (Rf =0.48, TLC, hexane/ethyl acetate, 25/75) and concentrated in vacuo to give (E)-4-chloro-N,N-diethyl-2-pentenamide. 4-Amino-6-chloro-2-mercaptopyrimidine mesylate (0.56 g, 2.19 mmol) is dissolved in DMF (4 ml) and sodium hydride (0.12 g, 4.82 mmol) at ambient temperature followed by the addition of (E)-4-chloro-N,N-diethyl-2-pentenamide (0.41 g, 2.19 mmol). The reaction is stirred for 15 hours, quenched with excess water, extracted with ethyl acetate (3×25 ml). The extracts are combined, washed with saline (25 ml), dried over sodium sulfate, concentrated in vacuo and chromatographed on silica gel (230-400 mesh, 100 ml), eluting with a gradient of hexane/ethyl acetate (80/20-60/40). The appropriate fractions are combined (Rf =0.27, TLC, hexane/ethyl acetate, 25/75) and concentrated in vacuo to give the title compound, mp 152-153° C.

Workup

  1. customquenched with excess water
  2. extractionextracted with ethyl acetate (3×25 ml)
  3. washwashed with saline (25 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 a gradient of hexane/ethyl acetate (80/20-60/40)
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-edfd0e685eb742168af42af73c8413ab
Source dataset
uspto-grants-2000_03
Patent number
US06043248

Reaction notes

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