Hydrochloric Acid → HCID 66719153, compound

Participants

Reaction Conditions

Reaction Steps

1-(1-(2-(Pyrrolidin-1-yl)ethyl)-1H-indazol-5-yl)-4-(trimethylstannyl)pyridin-2(1H)-one (prepared according to Example 30, step a) (250 mg, 0.530 mmol), 5-methyl-2-(methylthio)benzo[d]oxazole (198 mg, 1.11 mmol), copper(II) bromide (331 mg, 1.16 mmol) and palladium tetrakistriphenylphosphine (61 mg, 0.053 mmol) were stirred in dry THF (6 mL) under a nitrogen atmosphere. The mixture was heated to 70° C. for 20 h. Upon cooling, the mixture was diluted with THF, filtered through celite and rinsed with THF/methylene chloride. The organics were concentrated and purified by flash chromatography (40 g ISCO column eluting with methylene chloride and methanol/ammonia (10:1); 100% methylene chloride to 15% methanol/ammonia over 35 min at 40 mL/min) then further purified by Preparatory HPLC. The appropriate fractions were concentrated and partitioned between methylene chloride and Na2CO3. The organics were dried with Na2SO4, filtered, and concentrated to provide the free base. This was dissolved in methylene chloride (2 mL) and treated with 1 equivalent of 2 M HCl in Et2O, and the mixture was concentrated to provide the title compound (55.8 mg, 24%) as a yellow solid: mp 270-280° C.; 1H NMR (500 MHz, CD3OD) δ 8.27 (s, 1H), 7.94 (d, J=1.7 Hz, 1H), 7.88 (d, J=7.1 Hz, 1H), 7.83 (d, J=8.9 Hz, 1H), 7.64-7.61 (m, 2H), 7.58-7.55 (dd, J=8.9, 1.9 Hz, 1H), 7.44 (d, J=1.7 Hz, 1H), 7.37 (d, J=8.4 Hz, 1H), 7.24-7.22 (dd, J=7.1, 1.9 Hz, 1H), 4.89 (t, J=5.7, 2H), 3.88 (t, J=5.7, 2H), 3.74-3.70 (m, 2H), 3.21-3.16 (m, 2H), 2.51 (s, 3H), 2.20-2.16 (m, 2H) 2.04-2.01 (m, 2H); ESI MS m/z 440 [M+H]+; HPLC (Method C) 98.7% (AUC), tR=13.1 min.

Provenance & Evidence