2-Methyl-3-butyn-2-ol → 4-(4-(1-ethyl-7-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenyl)-2-methylbut-3-yn-2-ol

Participants

Reaction Conditions

Reaction Steps

To a microwave vial was added CuI (2.7 mg, 0.014 mmol), PdCl2(PPh3)2 (0.040 g, 0.056 mmol), PPh3 (0.059 g, 0.23 mmol), 4-(4-bromo-2-methylphenyl)-1-ethyl-7-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepine (0.500 g, 1.13 mmol, prepared using B from Example #2, step A with ethyl hydrazine oxalate, J with 4-bromobenzaldehyde and 1-sulfanylpropan-2-one [Enamine] and K with Na(OAc)3BH) as a solution in DMF (3.76 ml), 2-methylbut-3-yn-2-ol (0.197 ml, 2.26 mmol) and TEA (2.36 ml, 16.9 mmol). The vial was sealed and the solution was sparged with N2 for about 15 min. The mixture was heated in a microwave (300 W, pressure limit 250 atm) at 150° C. for 6 h. The mixture was diluted with water (25 mL) and extracted with EtOAc (2×25 mL). The organic layer was washed with water (25 mL), brine (25 mL), dried with MgSO4, filtered and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel; heptane/EtOAc 1:0 to 0:1) to give 4-(4-(1-ethyl-7-methyl-3-(pyridin-2-yl)-4,6,7,8-tetrahydro-1H-pyrazolo[3,4-e][1,4]thiazepin-4-yl)-3-methylphenyl)-2-methylbut-3-yn-2-ol (0.3 g, 59% yield); LC-MS (Table 1, Method g) Rt=2.52 and 2.55 min.; MS m/z: 447.17 and 447.17 (M+H)+.

Provenance & Evidence