Ethyl 1-[5-[2-(3-ethyl-5-methyl-2-oxo-1,3,5-triazinan-1-yl)-7-methoxy-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylate → 1-[5-[2-(Ethylcarbamoylamino)-7-methoxy-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid

Participants

Reaction Steps

Ethyl 1-[5-[2-(3-ethyl-5-methyl-2-oxo-1,3,5-triazinan-1-yl)-7-methoxy-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylate (225 mg, 0.41 mmol) was dissolved in a mixture of NaOH (1M) (1 mL) and THF (3 mL) and the mixture stirred at rt for 3 hrs. A further portion of NaOH (1M) (1 mL) was added and stirring at rt continued for a further 1 hr. The reaction was heated at 60° C. for 16 hrs then at 100 C for 2 hrs and then with a further portion of NaOH (1 M, 1 mL) for 4 hrs. 5 M NaOH solution (1 mL, 5 mmol) was added and stirring continued at rt overnight, followed by 60° C. for 2 hrs. The reaction mixture was concentrated by freeze-drying then purified using reverse-phase chromatography (C18 column), eluting with 20-60% ACN gradient in water (with 0.1% formic acid), to give Compound 200 (60 mg, light yellow solid). 1H NMR (MeOD) δ 8.63 (s, 2H), 7.43 (s, 1H), 6.94 (s, 1H), 4.45-4.35 (m, 2H), 4.05 (s, 3H), 3.46-3.35 (m, 4H, obscured by solvent), 2.23-2.16 (m, 2H), 1.53-1.42 (m, 2H), 1.28 (s, 3H), 1.24 (t, J=7.2 Hz, 3H). [M+H]+471.1.

Provenance & Evidence