Lithium Hexamethyldisilazide → HCID 68279566, compound

Participants

Reaction Steps

A vial was charged with (S)-3-chloro-7-(2-fluoropyridin-3-yl)-6′,7′-dihydro-2′H-spiro[chromeno[2,3-c]pyridine-5,5′-[1,4]oxazepin]-3′-amine (50.0 mg, 0.122 mmol), 3,3-difluoropyrrolidine hydrochloride (36.0 mg, 0.243 mmol), and RuPhos precatalyst (8.87 mg, 0.012 mmol). The vial was flushed with N2 gas, then lithium bis(trimethylsilyl)amide (1M in THF) (608 μl, 0.608 mmol) was added slowly to the mixture. After about 10 mins, the mixture was diluted with saturated aqueous ammonium chloride and extracted with EtOAc. The combined organic extracts were dried over MgSO4, filtered, and concentrated. The residue was purified on a 12 g Redi-Sep Gold silica-gel column eluting with a 90:10:1 mixture of DCM/MeOH/NH4OH in EtOAc to provide (S)-3-(3,3-difluoropyrrolidin-1-yl)-7-(2-fluoropyridin-3-yl)-6′,7′-dihydro-2′H-spiro[chromeno [2,3-c]pyridine-5,5′-[1,4]oxazepin]-3′-amine as off white solid. 1H NMR (500 MHz, DMSO-d6) δ ppm 2.06 (br. s., 1 H) 2.14 (br. s., 1 H) 2.51-2.61 (m, 2 H) 3.33-3.41 (m, 2 H) 3.58 (t, J=7.59 Hz, 2 H) 3.81 (t, J=13.04 Hz, 2 H) 4.34-4.46 (m, 2 H) 6.00 (br. s., 2 H) 6.57 (s, 1 H) 7.28 (d, J=8.33 Hz, 1 H) 7.48 (t, J=5.34 Hz, 1 H) 7.53 (d, J=8.76 Hz, 1 H) 7.62 (s, 1 H) 8.00-8.07 (m, 1 H) 8.10 (s, 1 H) 8.22 (d, J=4.06 Hz, 1 H).

Provenance & Evidence