1,2-Dimethoxyethane → N-(4-(Chlorodifluoromethoxy)phenyl)-4-((3S,4S)-3,4-dihydroxypyrrolidin-1-yl)-3-(pyrimidin-5-yl)benzamide

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Reaction Steps

3-Bromo-N-(4-(chlorodifluoromethoxy)phenyl)-4-((3S,4S)-3,4-dihydroxypyrrolidin-1-yl)benzamide (Stage 244.1, 80 mg, 0.167 mmol), pyrimidin-5-ylboronic acid (41.5 mg, 0.335 mmol), Pd(PPh3)2Cl2 (11.76 mg, 0.017 mmol) and Na2CO3 (71.0 mg, 0.670 mmol) were added to a MW vial and treated with a mixture of DME (710 μL), water (203 μL) and EtOH (101 μL). The vial was sealed, evacuated/purged with argon and subjected to MW irradiation at 125° C. for 10 min, diluted with MeOH (1 mL) and DCM (2 mL), treated with Si-Thiol (Silicycle, 1.44 mmol/g, 69.8 mg, 0.1 mmol). The solvent was evaporated off under reduced pressure to give a crude product that was purified by flash chromatography (RediSep® Silica gel column, 12 g, DCM/(MeOH-1% NH4OH), from 2% to 12% (MeOH-1% NH4OH). Product was further purified by preparative SFC (Column DEAP, from 25% to 30% in 10 min) to yield the title product as a white solid. UPLC-MS (Condition 3) tR=0.90 min, m/z=476.9 [M+H]+, m/z=521.0 [M+ formic acid-H]; 1H-NMR (400 MHz, DMSO-d6) δ ppm 2.75 (d, J=10.39 Hz, 2H) 3.27 (dd, J=10.33, 3.61 Hz, 2H) 3.88 (br. s, 2H) 5.09 (d, J=3.18 Hz, 2H) 6.97 (d, J=8.93 Hz, 1H) 7.33 (d, J=9.05 Hz, 2H) 7.82-7.90 (m, 3H) 7.94 (dd, J=8.80, 2.20 Hz, 1H) 8.86 (s, 2H) 9.17 (s, 1H) 10.11 (s, 1H).

Provenance & Evidence