Potassium Phosphate, Tribasic → HCID 89980399, compound

Participants

Reaction Conditions

Reaction Steps

Example 96-1. 9-bromo-2-(4-(methoxymethyl)-1H-imidazol-1-yl)-7,8-dihydro-[1,4]diazepino[7,1-a]isoquinolin-5(4H)-one (7.73 g, 19.26 mmol) was dissolved in toluene (155 mL) and S-Phos (2.58 g, 6.16 mmol), cyclopropylboronic acid (3.45 g, 38.5 mmol) and K3PO4 (8.59 g, 40.5 mmol) were added. The suspension was degassed, Pd(OAc)2 (0.87 g, 3.85 mmol) was added under Argon and the mixture was heated at 100° C. for 1 h. The mixture was allowed to warm to RT and filtered through a pad of celite. The residue was diluted with DCM and extracted with water, saturated aqueous NaHCO3 solution and brine. The combined organic layers were dried with sodium sulfate, filtered and the solvent was removed under reduced pressure. The crude product was purified by flash-column chromatography over silicagel (Biotage Isolera Four, eluent: 1% MeOH in DCM for 5 min, then from 1% MeOH in DCM to 5% MeOH in DCM in 60 min, 5% MeOH in DCM for 10 min) to yield a beige foam (6.85 g). The residue was crystallized from AcOEt to afford the title compound as white crystals (5.8 g). UPLC-MS: MS 363.3 (M+H+); UPLC rt 0.95 min. 1H NMR (400 MHz, DMSO-d6): δ ppm 0.50-0.72 (m, 2 H), 0.79-1.06 (m, 2 H), 1.77-2.08 (m, 1 H), 2.93-3.14 (m, 2 H), 3.24 (s, 3 H), 3.87 (br. s, 2 H), 4.13-4.39 (m, 4 H), 7.09-7.21 (m, 2 H), 7.24-7.35 (m, 1 H), 7.62 (s, 1 H), 7.84-7.94 (m, 1 H), 8.20 (s, 1 H).

Provenance & Evidence