Cesium carbonate → HCID 67130049, compound

Participants

Reaction Conditions

Reaction Steps

In a flask, RuPhos (3.63 g, 7.79 mmol) and Pd2dba3 (3.56 g, 3.89 mmol) were combined in t-AmOH (100 mL). The mixture was degassed by bubbling N2 into the solution. The mixture was heated to about 60° C. for about 30 min. Then Cs2CO3 (38.3 g, 117 mmol), tert-butyl 6-amino-3-methyl-1H-indazole-1-carboxylate (16.0 g, 64.9 mmol), and 2-chloro-N-cyclopropylfuro[3,2-d]pyrimidin-4-amine (13.6 g, 64.9 mmol) were added in one portion. To the mixture was added t-AmOH (200 mL) and the mixture was placed under vacuum, purged with N2, and then stiffed at about 75° C. for about 15 h. The mixture was filtered through a plug of Celite®. The filtrate was concentrated and redissolved in DCM (50 mL). The mixture was purified by column chromatography (0-2.5% MeOH in DCM over 30 min on 330 g silica gel) to give a solid. The solid was dissolved in DCM (20 mL) and after about 10 min at rt, a thick precipitate formed which was collected via filtration. The solid was washed with DCM (25 mL) and dried in a vacuum oven at about 70° C. for about 12 h to give tert-butyl 6-(4-(cyclopropylamino)furo[3,2-d]pyrimidin-2-ylamino)-3-methyl-1H-indazole-1-carboxylate (12.5 g, 46%); LC/MS (Table 2, Method c) Rt=2.29 min.; MS m/z: 421 (M+H)+, 1H NMR (400 MHz, CDCl3) δ 8.76 (s, 1H), 7.64 (d, J=2.1 Hz, 1H), 7.50 (d, J=8.6 Hz, 1H), 7.42 (dd, J=8.6, 1.8 Hz, 1H), 7.26 (s, 1H), 6.67 (d, J=2.1 Hz, 1H), 5.29 (s, 1H), 3.20-3.12 (m, 1H), 2.55 (s, 3H), 1.72 (s, 9H), 0.99-0.91 (m, 2H), 0.71-0.64 (m, 2H).

Provenance & Evidence