Diisopropylethylamine → HCID 86680151, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 5-((4-methoxyphenyl)methoxy)-1-(2-methyl-4-nitro-pyrazol-3-yl)azepan-4-ol (0.80 g, 2.18 mmol) in EtOH (30 mL) and water (3 mL) was added iron powder (0.90 g, 16.11 mmol) The reaction mixture was heated at 100° C. for 2 hr, cooled to room temperature, filtered through Celite® and the filtrate concentrated under reduced pressure. The residue was dissolved in DCM (50 mL) and washed with water (50 mL). The aqueous layer was re-extracted with DCM (50 mL) and the combined organic layers passed through a phase separation cartridge and concentrated under reduced pressure to give a pale orange gum. To a solution of this gum (0.55 g, 1.60 mmol) in DMF (5 mL) was added 5-(tert-butoxycarbonylamino)-2-(2,6-difluorophenyl)thiazole-4-carboxylic acid (0.62 g, 1.76 mmol), HATU (0.85 g, 2.40 mmol) and DIPEA (0.56 mL, 3.20 mmol). The reaction mixture was stirred at room temperature for 66 hr, quenched with a saturated aqueous NaHCO3 (200 mL) and extracted with EtOAc (3×150 mL). The combined organic layers were washed with brine (100 mL), separated, dried over MgSO4 and concentrated under reduced pressure. Purification via silica gel column chromatography (0-10% MeOH/EtOAc) gave tert-butyl N-(2-(2,6-difluorophenyl)-4-((5-(4-hydroxy-5-((4-methoxyphenyl)methoxy)azepan-1-yl)-1-methyl-pyrazol-4-yl)carbamoyl)thiazol-5-yl]carbamate as a pale pink solid (530 mg, 35% over two steps). 1H NMR (400 MHz, CDCl3) δ 10.44 (s, 1H), 9.02 (s, 1H), 7.91 (s, 1H), 7.38-7.28 (m, 1H), 7.25 (d, J=8.2 Hz, 2H), 7.00 (t, J=8.7 Hz, 2H), 6.92-6.84 (m, 2H), 4.61 (d, J=11.1 Hz, 1H), 4.40 (d, J=11.1 Hz, 1H), 3.91 (t, J=8.6 Hz, 1H), 3.81 (s, 3H), 3.73 (s, 3H), 3.55 (td, J=8.4, 3.4 Hz, 1H), 3.34-3.13 (m, 4H), 3.10 (s, 1H), 2.22-2.14 (m, 2H), 1.93-1.77 (m, 2H), 1.62-1.50 (m, 9H).

Provenance & Evidence