Sodium hydride → methyl (E)-4-(4-amino-6-chloro-pyrimidin-2-yl)sulfanyl-3-methyl-pent-2-enoate

HRID 1637728Notes

Reaction equation

HRID 1637728 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+].[CH3:17][O:18][C:19](=[O:26])/[CH:20]=[C:21](\[CH3:25])/[CH:22](Cl)[CH3:23]>CN(C=O)C>[CH3:17][O:18][C:19](=[O:26])/[CH:20]=[C:21](\[CH3:25])/[CH:22]([S:14][C:9]1[N:8]=[C:7]([NH2:6])[CH:12]=[C:11]([Cl:13])[N:10]=1)[CH3:23]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 86755256(E)-4-chloro-3-methyl-2-pentenoic acid methyl esterHCID 178505342HCID 178505342, compound

Product 1

HCID 6476889methyl (E)-4-(4-amino-6-chloro-pyrimidin-2-yl)sulfanyl-3-methyl-pent-2-enoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To (E)-4-hydroxy-3-methyl-2-pentenoic acid methyl ester (1.00 g, 6.94 mmol) in methylene chloride cooled to -15° C. in a flame dried flask is added dichlorotriphenylphosphorane (2.47 g, 7.63 mmol). The reaction is warmed to ambient temperature, quenched by addition of ice (10 ml), extracted with methylene chloride (2×10 ml), washed with saline (10 ml), dried over sodium sulfate, concentrated in vacuo, and chromatographed on silica gel (230-400 mesh, 75 ml), eluting with hexane/ethyl acetate (95/5). The appropriate fractions are combined (Rf =0.55, TLC, hexane/ethyl acetate, 75/25) and concentrated in vacuo to give (E)-4-chloro-3-methyl-2-pentenoic acid methyl ester. 4-Amino-6-chloro-2-mercaptopyrimidine mesylate (0.30 g, 1.16 mmol) is dissolved in DMF (4 ml) and sodium hydride (0.06 g, 2.56 mmol) at ambient temperature followed by the addition of (E)-4-chloro-3-methyl-2-pentenoic acid methyl ester (0.19 g, 1.16 mmol). The reaction is stirred for 15 hours, quenched with excess water, extracted with ethyl acetate (3×15 ml). The extracts are combined, washed with saline (15 ml), dried over sodium sulfate, concentrated in vacuo and chromatographed on silica gel (230-400 mesh, 100 ml), eluting with hexane/ethyl acetate (85/15). The appropriate fractions are combined (Rf =0.18, TLC, hexane/ethyl acetate, 50/50) and concentrated in vacuo to give the title compound, mp 124-126° C.

Workup

  1. customquenched with excess water
  2. extractionextracted with ethyl acetate (3×15 ml)
  3. washwashed with saline (15 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 (85/15)
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e47ac45a9efa47b8a0617fcb654a2815
Source dataset
uspto-grants-2000_03
Patent number
US06043248

Reaction notes

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