Diisopropylethylamine → HCID 86680041, compound

Participants

Reaction Steps

A solution of tert-butyl N-(−2-methoxy-5-(2-methyl-4-nitro-pyrazol-3-yl)cyclohept-4-en-1-yl)carbamate (180 mg, 0.49 mmol) in MeOH (30 mL) was passed through the H-Cube® (full H2, 70° C., flow rate: 1 mL/min, 30 mm 20% Pd/C cartridge). The solvent was removed under reduced pressure to give a colourless oil. To a solution of this oil in DCM (30 mL) was added DIPEA (2.00 mL, 11.48 mmol) and 5-(tert-butoxycarbonylamino)-2-(2-fluorophenyl)thiazole-4-carboxylic acid (171 mg, 0.50 mmol) followed by PyBOP (596 mg, 1.15 mmol) and the mixture was stirred at room temperature for 16 hr. The reaction was quenched with water (20 mL) and extracted with DCM (80 mL). The organic layer was separated, dried over MgSO4 and concentrated under reduced pressure. Purification via silica gel chromatography (70-80% EtOAc/isohexane) gave tert-butyl N-(5-(4-((5-(tert-butoxycarbonylamino)-2-(2,6-difluorophenyl)thiazole-4-carbonyl)amino)-2-methyl-pyrazol-3-yl]-2-methoxy-cycloheptyl]carbamate as a mixture of four diastereomers as an off-white solid (175 mg, 54% over two steps). 1H NMR (400 MHz, CDCl3) δ 10.39 and 10.36 (2s, 1H), 8.69 and 8.62 (2s, 1H), 8.32-8.28 and 8.21-8.14 (2 m, 1H), 7.85 and 7.75 (2s, 1H), 7.43-7.36 (m, 1H), 7.32 (t, J=7.6 Hz, 1H), 7.25-7.17 (m, 1H), 5.19 and 5.08 (2d, J=8.8 Hz, 1H), 3.84 (s, 3H), 3.78-3.54 (m, 2H), 3.37 and 3.27 (2s, 3H), 3.11-2.94 (m, 1H), 2.32-1.30 (m, 8H), 1.55 (s, 9H), 1.43 (s, 9H).

Provenance & Evidence