L-Hydroxyproline → HCID 66558505, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 9-bromo-2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine 95 from Example 95 (100 mg, 0.27 mmol), (S)-pyrrolidinylmethylpyrrolidine (206 mg, 1.34 mmol), K3PO4 (114 mg, 0.53 mmol), trans-4-hydroxyproline (14 mg, 0.11 mmol) and CuI (10 mg, 0.05 mmol) in DMSO (0.5 mL) was heated at 90° C. for 23 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 dissolved in DCM and washed with 10% citric acid, dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, gradient 0-6% MeOH in DCM) then 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 133 (22 mg, 19%) as a white solid. LCMS: RT 2.81 min [M+H]+ 448.4. 1H NMR (DMSO, 400 MHz): δ 8.19 (1H, d, J=8.93 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), 5.93-5.92 (1H, m), 4.48-4.36 (4H, m), 3.89-3.81 (1H, m), 3.42-3.35 (1H, m), 3.15-3.05 (1H, m), 2.64-2.57 (2H, m), 2.43-2.40 (4H, m), 2.00-1.98 (4H, m), 1.74-1.66 (4H, m), 1.47 (6H, d, J=6.61 Hz)

Provenance & Evidence