Hydrochloric Acid → 6-Amino-5-chloro-2-(4-chloro-2-fluorophenyl)pyrimidine-4-carboxylic acid ethyl ester

HRID 1807372Notes

Reaction equation

Cl.[C:2](Cl)(=O)[CH3:3].[NH2:6][C:7]1[N:12]=[C:11]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=2[F:20])[N:10]=[C:9]([C:21]([OH:23])=[O:22])[C:8]=1[Cl:24].C(OCC)(=O)C.CCCCCC>C(O)C>[CH2:2]([O:22][C:21]([C:9]1[C:8]([Cl:24])=[C:7]([NH2:6])[N:12]=[C:11]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=2[F:20])[N:10]=1)=[O:23])[CH3:3]

Participants

Conditions

Temperature: 62 °C

Procedure

A 1N solution of HCl in ethanol was generated by adding 0.565 mL of acetyl chloride dropwise to 12 mL of ethanol cooled in an ice bath. This solution was added to 200 mg of 6-amino-5-chloro-2-(4-chloro-2-fluorophenyl)-pyrimidine-4-carboxylic acid and the resulting solution was heated at 62° C. overnight. The reaction mixture was concentrated and the residue partitioned between ethyl acetate and water. The organic phase was dried and concentrated, and the product was purified by column chromatography (dichloromethane/ethyl acetate gradient). A second chromatography utilizing an amine-functionalized silica gel column (Biotage KP-NH) and an ethyl acetate/hexane gradient solvent system yielded the title compound (139 mg, 63.5% yield): mp 131-132° C.: 1H NMR (CDCl3): δ 7.97 (m, 1H), 7.2 (m, 2H), 5.63 (br s, 2H), 4.48 (q, 2H), 1.44 (t, 3H).

Workup

temperaturecooled in an ice bath
concentrationThe reaction mixture was concentrated
customthe residue partitioned between ethyl acetate and water
customThe organic phase was dried
concentrationconcentrated
customthe product was purified by column chromatography (dichloromethane/ethyl acetate gradient)

Sources & evidence

ORD record: ord-b38b760175a740a4838628ea5fd90741
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08357633B2

Reaction notes

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