Nitrogen → 1-[5-[2-(ethylcarbamoylamino)-7-[(E)-methoxyiminomethyl]-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methylpiperidine-4-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

A stirred solution of (E)-2-(3-ethylureido)-7-((methoxyimino)methyl)benzo[d]thiazol-5-yl trifluoromethanesulfonate (225 mg, 0.34 mmol), bis(neopentyl)glycolatodiboron (180 mg, 0.8 mmol) and potassium acetate (100 mg, 1.02 mmol) in anhydrous DMF (3.5 ml) was purged with N2 for 15 min. 1,1′-bis(diphenylphosphino)ferrocene palladium(II)chloride (30 mg, 0.034 mmol) was added, the reaction vessel was sealed and heated at 80° C. for 2 h. The reaction mixture was cooled to ambient temperature, treated with 1-(5-bromopyrimidin-2-yl)-4-methylpiperidine-4-carboxylic acid (120 mg, 0.4 mmol) followed by aqueous cesium carbonate solution (3.7M 0.5 ml, 0.343 mmol). The reaction mixture was purged with N2 for 5 min, treated with 1,1′-bis(diphenylphosphino)ferrocene palladium(II)chloride (30 mg, 0.034 mmol), sealed and heated at 80° C. for 2 h. The reaction was allowed to cool, filtered and Compound 72 purified by preperative HPLC as a brown solid (40 mg, LC-MS indicated 97% purity) (24%). 1H NMR (CH3OH-d4): δ 8.67 (2H, s), 8.40 (1H, s), 7.86 (1H, d, J=1.66 Hz), 7.53 (1H, d, J=1.67 Hz), 4.42 (2H, dt, J=13.74, 4.26 Hz), 4.11 (3H, s), 3.45-3.32 (2H, m), 2.21 (2H, dt, J=13.45, 3.31 Hz), 1.49 (2H, ddd, J=13.45, 10.71, 4.04 Hz), 1.30 (3H, s), 1.26 (3H, t, J=7.28 Hz). MS: 498 [M+H]+

Provenance & Evidence