Sodium hydride → 6-Chloro-2-[1-(4-ethyl-5-methoxy-2-pyridyl)ethylsulfanyl]pyrimidin-4-amine

HRID 1637772Notes

Reaction equation

HRID 1637772 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]1[CH:20]=[N:21][C:22]([CH:27](Cl)[CH3:28])=[CH:23][C:24]=1[CH2:25][CH3:26]>CN(C)C=O.C(OCC)(=O)C>[NH2:6][C:7]1[CH:12]=[C:11]([Cl:13])[N:10]=[C:9]([S:14][CH:27]([C:22]2[CH:23]=[C:24]([CH2:25][CH3:26])[C:19]([O:18][CH3:17])=[CH:20][N:21]=2)[CH3:28])[N:8]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 187997473-Methoxy-4-ethyl-6-(1-chloroethyl)-pyridineHCID 178505342HCID 178505342, compound

Product 1

HCID 4928036-Chloro-2-[1-(4-ethyl-5-methoxy-2-pyridyl)ethylsulfanyl]pyrimidin-4-amineYield 71.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 4-amino-6-chloro-2-mercapto-pyrimidine mesylate salt (290 mg, 1.1 mmol) in 2 mL of N,N-dimethylformamide at 0° C. is treated with 92 mg (60% in oil, 2.3 mmol) of sodium hydride and warmed to room temperature for 1 h. A solution of 3-methoxy-4-ethyl-6-(1-chloroethyl)-pyridine (225 mg, 1.1 mmol) in 2×1 mL of N,N-dimethylformamide is added dropwise to the mixture and the reaction was stirred for 18 h. The reaction is diluted with 50 mL of ethyl acetate, was washed with 4×25 mL of 50% saturated sodium chloride and dried over potassium carbonate. The organics are concentrated in vacuo and the crude material is chromatographed over 20 g of silica gel (230-400 mesh), eluting with 50% ethyl acetate/hexanes to afford 256 mg of an oil which upon crystallization from ether gave 188 mg (53%) of Cpd #245 (Melting Pt. 136-137° C.).

Workup

  1. washwas washed with 4×25 mL of 50% saturated sodium chloride
  2. dry with materialdried over potassium carbonate
  3. concentrationThe organics are concentrated in vacuo
  4. customthe crude material is chromatographed over 20 g of silica gel (230-400 mesh)
  5. washeluting with 50% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-20286445ac59494bb67dd82dc4e41552
Source dataset
uspto-grants-2000_03
Patent number
US06043248

Reaction notes

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