L-Hydroxyproline → HCID 66558671, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 8-bromo-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene, also named as 9-bromo-2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine 95 (200 mg, 0.27 mmol), (R)-pyrrolidynlmethylpyrrolidine (412 mg, 1.33 mmol), K3PO4 (228 mg, 0.53 mmol), CuI (20 mg, 0.05 mmol) and L-4-transhydroxyproline (14 mg, 0.11 mmol) in DMSO (1 mL) was heated at 100° C. for 18 h. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH. The resulting residue was purified by column chromatography (Si-PCC, gradient 0-10% MeOH in DCM then C18, gradient 5-45% MeOH in H2O). The resulting residue was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH. The resulting residue was freeze-dried from MeCN/H2O to afford 144 (41 mg, 34%) as a white solid. LCMS: RT 4.78 min [M+H]+ 448.4. 1H NMR (DMSO, 400 MHz): δ 8.19 (1H, d, J=8.92 Hz), 7.88 (1H, d, J=0.63 Hz), 7.77 (1H, s), 6.45 (1H, dd, J=9.00, 2.43 Hz), 6.13 (1H, d, J=2.38 Hz), 5.96-5.93 (1H, m), 4.47-4.36 (4H, m), 3.89-3.81 (1H, m), 3.40-3.38 (1H, m), 3.14-3.04 (1H, m), 2.64-2.57 (2H, m), 2.50-2.34 (4H, m), 1.98-1.96 (4H, m), 1.74-1.66 (4H, m), 1.47 (6H, d, J=6.61 Hz)

Provenance & Evidence