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

Temperatur

150 °C

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)+.

1. customThe vial was sealed
2. customthe solution was sparged with N2 for about 15 min
3. additionThe mixture was diluted with water (25 mL)
4. extractionextracted with EtOAc (2×25 mL)
5. washThe organic layer was washed with water (25 mL), brine (25 mL)
6. dry with materialdried with MgSO4
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe crude material was purified by flash chromatography (silica gel; heptane/EtOAc 1:0 to 0:1)

ORD-Eintrag

ord-33a9b522c04a4117993ea5fac5c290d2

Quelldatensatz

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09150592B2