4-Amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-ethenyl-6-methoxycarbonylpyrimidine → 6-Amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-ethyl-pyrimidine-4-carboxylic acid methyl ester

HRID 245286Notes

Reaction equation

HRID 245286 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:10]([CH:11]=[CH2:12])=[C:9]([NH2:13])[N:8]=[C:7]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[C:16]([O:21][CH3:22])[C:15]=2[F:23])[N:6]=1)=[O:4]>C(O)C.[OH-].[Pd+2].[OH-]>[CH3:1][O:2][C:3]([C:5]1[C:10]([CH2:11][CH3:12])=[C:9]([NH2:13])[N:8]=[C:7]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[C:16]([O:21][CH3:22])[C:15]=2[F:23])[N:6]=1)=[O:4]

Participants

4

Reactant 1

HCID 594321224-Amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-ethenyl-6-methoxycarbonylpyrimidine

Product 1

HCID 594321126-Amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-ethyl-pyrimidine-4-carboxylic acid methyl esterYield 62.2%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 702EthanolSolvent

Procedure

6-Amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-vinyl-pyrimidine-4-carboxylic acid methyl ester (200 mg, 0.7 mmol) was dissolved in ethanol (10 mL), palladium hydroxide (20% on carbon, 50 mg) was added, and the reaction mixture was stirred under an atmosphere of hydrogen for 4 h. The catalyst was then filtered off, the filtrate concentrated, and the product purified by flash chromatography on silica gel (hexane/ethyl acetate gradient) to yield the title compound (148 mg, 62% yield): mp 144-146° C.: 1H NMR (CDCl3) δ 7.61 (m, 1H), 7.20 (m, 1H), 5.19 (br s, 2H), 3.99 (d, 3H), 3.98 (s, 3H), 2.68 (q, 2H), 1.28 (t, 3H).

Workup

  1. filtrationThe catalyst was then filtered off
  2. concentrationthe filtrate concentrated
  3. customthe product purified by flash chromatography on silica gel (hexane/ethyl acetate gradient)

Sources & evidence

ORD record
ord-ffee27ab220d4a13a6ff1dbd87348a7f
Source dataset
uspto-grants-2014_02
Patent number
US08658791B2

Reaction notes

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