Hydrochloric Acid → HCID 178441168, compound

Participants

Reaction Steps

To a solution of tert-butyl 4-(1H-indol-5-yloxy)-5-methyl-5H-pyrrolo[3,4-d]pyrimidine-6 (7H)-carboxylate (150 mg, 0.409 mmol) in DMF (4 mL) at rt, di(1H-imidazol-1-yl)methanone (86 mg, 0.532 mmol) is added followed by TEA (0.34 mL, 2.46 mmol). After 3 h at room temperature 5-tert-butyl-1H-pyrazol-3-amine (342 mg, 2.46 mmol) is added and the reaction left stirring at rt for 48 h. At this point as 1N HCl solution in water (2 mL) is added and EtOAc (5 mL) is added. The layers are separated and the water layer extracted 3 times with EtOAc. The organics are dried and evaporated. DCM (4 mL) and TFA (10 mL, 130 mmol) are added at 0° C. and the reaction allowed to warm to rt over 1 h. At this point the reaction is complete. TFA/DCM is evaporated and then the product is taken up in EtOAc (100 mL). NH4OH (20 mL) is added and then water. The organics are separated and the water layer extracted with EtOAc (2 times). The organics are dried and evaporated. The crude product is added to a silica gel column (ISCO) and eluted with DCM/MeOH/NH4OH (100:0:0 to 93:6:1) to isolate 5-methyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yloxy)-indole-1-carboxylic acid (5-tert-butyl-2H-pyrazol-3-yl)-amide. MS (ESI) m/z 432.0 (M+1); 1H NMR (400 MHz, MeOD) δ ppm 8.50 (s, 1H) 8.33 (d, J=9.09 Hz, 1H) 7.89 (d, J=3.54 Hz, 1H) 7.41 (d, J=2.27 Hz, 1H) 7.10 (dd, J=8.97, 2.40 Hz, 1H) 6.71 (d, J=3.54 Hz, 1H) 6.37 (s, 1H) 4.71 (d, J=6.57 Hz, 1H) 4.10-4.22 (m, 2H) 1.60 (d, J=6.82 Hz, 3H) 1.37 (s, 9H).

Provenance & Evidence