Ammonia → HCID 71542227, compound

Participants

Reaction Steps

The title compound was synthesized analogous to step 1 (Method D) described in example 34, but using (S)—N-(3-bromo-7-iodo-5′,6′-dihydrospiro[chromeno[2,3-b]pyridine-5,4′-[1,3]oxazin]-2′-yl)benzamide (88 mg, 0.153 mmol, Intermediate 24B) and 5-methoxypyrazine-2-carboxamide (28.1 mg, 0.183 mmol). The residue from step 1 was dissolved in THF (1 mL) and treated with ammonia (2.0 M solution in methanol; 1.145 mL, 2.291 mmol) at 50° C. After 12 hours another portion of ammonia, (2.0 M solution in methanol; 1.145 mL, 2.291 mmol) was added and the reaction mixture was allowed to stir for additional 5 hours The solvent was removed under reduced pressure and the residue was purified by preparative reversed-phase HPLC using a Phenomenex Gemini column, 10 micron, C18, 110 Å, 100×50 mm, 0.1% TFA in CH3CNH2O, gradient 10% to 100% over 20 min. The combined fractions were concentrated. The residue was dissolved in MeOH and loaded onto a Varian Bond Elut SCX column. The product was eluted with a 2M solution of NH3 in MeOH. 10 mg of (S)—N-(2′-amino-3-bromo-5′,6′-dihydrospiro[chromeno[2,3-b]pyridine-5,4′-[1,3]oxazin]-7-yl)-5-methoxypyrazine-2-10 carboxamide were obtained as an off-white solid. MS m/z=497.1 [M]+. Calculated for C21H17BrN6O4: 497.30. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.82-1.92 (m, 1H) 1.94-2.04 (m, 1H) 4.08 (s, 3H) 4.11-4.18 (m, 1H) 4.20-4.30 (m, 1H) 7.31 (d, J=9.21 Hz, 1H) 7.69-7.77 (m, 2H) 7.94 (d, J=2.34 Hz, 1H) 8.18 (d, J=1.32 Hz, 1H) 8.32 (d, J=2.48 Hz, 1H) 9.04 (d, J=1.32 Hz, 1H) 9.55 (s, 1H).

Provenance & Evidence