CO[C:3]([CH:5]1[C:9](=O)[CH2:8][O:7][CH2:6]1)=[O:4].[F:11][C:12]1[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:13]=1[C:14]([NH2:16])=[NH:15]>C(O)C>[Cl:21][C:18]1[CH:19]=[CH:20][C:12]([F:11])=[C:13]([C:14]2[N:16]=[C:3]([OH:4])[C:5]3[CH2:6][O:7][CH2:8][C:9]=3[N:15]=2)[CH:17]=1To a suspension of 4-oxo-tetrahydrofuran-3-carboxylic acid methyl ester (prepared according to Dowd, P.; Choi, S-C. Tetrahedron, 1991, 47, 4847-4860; 800 mg, 5.55 mmol, 1 eq) in ethanol (20 ml) was added a solution of 2-fluoro-5-chlorobenzamidine (961 mg, 5.55 mmol, 1 eq) in EtOH (10 ml). The reaction mixture was heated to 80° C. overnight. The reaction mixture was cooled to rt and the white precipitate was filtered and washed with cold ethyl actetate (2×20 ml). The crude residue was partitioned between chloroform and water. The aqueous layer was acidified to pH 4 and the product was extracted with chloroform (3×50 ml). The organic layers were combined, washed with brine, dried over MgSO4, filtered and concentrated in vacuo to give a crude solid which was purified by flash column chromatography (5% MeOH in EtOAc) to give a white solid 2-(5-Chloro-2-fluorophenyl)-5,7-dihydrofuro[3,4-d]pyrimidin-4-ol (440 mg, 30%).
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