4-Chloroaniline → Ethyl 2-(4-chlorophenylamino)pyrimidine-5-carboxylate

HRID 77446Notes

Reaction equation

HRID 77446 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:4][N:3]=1.[Cl:13][C:14]1[CH:20]=[CH:19][C:17]([NH2:18])=[CH:16][CH:15]=1>O1CCOCC1.C(OCC)(=O)C>[Cl:13][C:14]1[CH:20]=[CH:19][C:17]([NH:18][C:2]2[N:7]=[CH:6][C:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:4][N:3]=2)=[CH:16][CH:15]=1

Participants

5

Reactant 2

HCID 78124-ChloroanilineHCID 104878152-Chloro-pyrimidine-5-carboxylic acid ethyl ester

Product 1

HCID 86679731Ethyl 2-(4-chlorophenylamino)pyrimidine-5-carboxylateYield 58%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of ethyl 2-chloropyrimidine-5-carboxylate (0.5 g, 2.68 mmol) and 4-chloroaniline (0.684 g, 5.36 mmol) in dioxane (15 mL) was heated at 100° C. for 8 h, diluted with ethyl acetate and filtered. The filtrate was concentrated and the residue was purified by flash chromatography on silica gel using 0-30% ethyl acetate in hexanes. The desired fractions were concentrated to give ethyl 2-(4-chlorophenylamino)pyrimidine-5-carboxylate as an orange solid (0.43 g, 58%). 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 8.96 (2H, s), 7.57-7.64 (2H, m), 7.45 (1H, br. s.), 7.29-7.36 (2H, m), 4.37 (2H, q, J=7.02 Hz), 1.38 (3H, t, J=7.02 Hz). LCMS: R.T.=4.16 min; [M+H]+=277.96.

Workup

  1. filtrationfiltered
  2. concentrationThe filtrate was concentrated
  3. customthe residue was purified by flash chromatography on silica gel using 0-30% ethyl acetate in hexanes
  4. concentrationThe desired fractions were concentrated

Sources & evidence

ORD record
ord-e4fcb5251d324f75a8fe9440a4457705
Source dataset
uspto-grants-2014_09
Patent number
US08841301B2

Reaction notes

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