Hydrochloric Acid → 2-hydroxy-4-(6-(1-methyl-1H-pyrazol-4-yl)-2-oxo-5-phenyl-1,2,3,4-tetrahydropyrimidin-4-yl)benzoic acid

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Reaction Conditions

Reaction Steps

A mixture of 1-(1-methyl-1H-pyrazol-4-yl)-2-phenylethanone (Intermediate 88) (150 mg, 0.75 mmol), methyl 4-formyl-2-hydroxybenzoate (Intermediate 84) (135 mg, 0.75 mmol), urea (138 mg, 2.3 mmol) and conc. HCl (0.5 mL) in EtOH (5 mL) was refluxed under N2 atmosphere overnight. The mixture was concentrated under reduced pressure. The residue was taken up in MeOH (10 mL) and aq. NaOH (2 M, 10 mL) and was stirred at 60° C. under N2 overnight. The mixture was cooled, and then acidified with aqueous HCl (2 M, 12 mL) to pH=3 followed by a standard aqueous/EtOAc workup and purification by prep-HPLC (0.1% TFA as additive) to give Compound 167 (58 mg, 2-step yield 20%) as off-white solid. 1H NMR (CD3OD 400 MHz): δ 7.81 (d, J=8.0 Hz, 1H), 7.38 (s, 1H), 7.25-7.20 (m, 3H), 6.88-6.78 (m, 3H), 6.84 (d, J=8.0 Hz, 1H), 6.82 (s, 1H), 5.17 (s, 1H), 3.77 (s, 3H). MS (ESI): m/z 390.7 [M+1]+.

Provenance & Evidence