Dichloromethane → Ethyl 1-[5-[2-(ethylcarbamoylamino)-6-methoxy-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylate

Participants

Reaction Conditions

Reaction Steps

1-(5-Bromo-6-methoxy-1,3-benzothiazol-2-yl)-3-ethyl-urea (Intermediate 11) (200 mg, 66 mass %, 0.40 mmol), ethyl 4-methyl-1-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-yl]piperidine-4-carboxylate (crude, 638 mg, 47 mass %, 0.80 mmol) and Pd(dppf)Cl2.DCM (16 mg, 0.02 mmol) were dissolved in dioxane (7.5 mL) in a microwave vial and a solution of cesium carbonate (391 mg, 1.20 mmol) in water (2.5 mL) was added. The vial was capped, the mixture degassed and heated in the microwave at 110° C. for 30 minutes. The mixture was poured into water, extracted into EtOAc (4×20 mL) and the organic layers washed with brine, dried over Na2SO4 and concentrated to dryness in vacuo. A yellow solid was obtained and the mixture purified by chromatography, Biotage SP4, 12 g Si cartridge, 0-5% MeOH in DCM. The relevant fractions were combined to give a brown solid which was further purified by chromatography, Biotage SP4, 12 g Si cartridge, 50% EtOAc in hexane (isocratic) then the column flushed with EtOAc. The relevant fractions were combined to give Compound 191 as a white solid, 110 mg (55%). 1H NMR (MeCN-d3): δ 1.19 (3H, t, J=7.2 Hz), 1.26 (3H, s), 1.29 (3H, t, J=7.1 Hz), 1.49 (2H, ddd, J=14.0, 10.5 and 4.1 Hz), 2.14 (2H, m), 3.32 (4H, m), 3.87 (3H, s), 4.20 (2H, q, J=7.1 Hz), 4.37 (2H, dt, J=14.0 and 4.1 Hz), 6.16 (1H, br s), 7.51 (1H, s), 7.61 (1H, s), 8.55 (2H, s), 8.77 (1H, br s). MS: 499.12 [M+H]+.

Provenance & Evidence