Sodium hydride → Tert-butyl 2-((tert-butoxycarbonyl)(5-(8-morpholino-2-((quinolin-2-yloxy)methyl)imidazo[1,2-a]pyrazin-5-yl)pyridin-2-yl)amino)acetate

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Reaction Steps

Compound 48a (200.0 mg, 0.450 mmol) was treated with 60% sodium hydride (19.2 mg, 0.48 mmol) in DMF (5 mL) for 15 min. tert-Butyl bromoacetate (25.6 mg, 0.25 mmol) was then added, and the resulting mixture was stirred for 5 h at rt. The reaction was diluted with EtOAc and washed with water. The organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (0-100% EtOAc/heptanes) to give tert-butyl 2-((tert-butoxycarbonyl)(5-(8-morpholino-2-((quinolin-2-yloxy)methyl)imidazo[1,2-a]pyrazin-5-yl)pyridin-2-yl)amino)acetate as an off-white solid, which was subsequently deprotected with TFA following the methods described in the Example 47, Step B to afford the title compound 107 as an off-white solid after trituration with ether. 1H-NMR (400 MHz, CD3OD) δ (ppm): 3.84-3.93 (m, 4H), 4.27 (s, 2H), 4.31-4.39 (m, 4H), 5.66 (s, 2H), 6.97 (d, J=8.8 Hz, 1H), 7.11 (d, J=9.0 Hz, 1H), 7.31 (s, 1H), 7.39-7.45 (m, 1H), 7.66 (ddd, J=8.4, 6.9, 1.3 Hz, 1H), 7.80 (d, J=8.3 Hz, 2H), 7.95-8.01 (m, 2H), 8.12-8.18 (m, 2H). Mass Spectrum (LCMS, ESI pos.) Calcd. For C27H25N7O4: 512.2 [M+H]. found 512.2.

Provenance & Evidence