Cesium carbonate → 1-Methyl-4-(2-methyl-4-methylsulfonyl-phenyl)-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine

温度

120 °C

To a degassed solution of 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.057 g, 0.1 mmol) and tris(dibenzylideneacetone)dipalladium(0) (0.045 g, 0.025 mmol) in toluene (6 mL) was added 4-(4-bromo-2-methyl-phenyl)-1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine (0.400 g, 0.96 mmol, Example #4 step D), cesium carbonate (0.470 g, 1.5 mmol) and sodium methanesulfinate (0.118 g, 1.2 mmol). The resulting mixture was heated at about 120° C. overnight. After cooling to rt, the mixture was diluted with ethyl acetate (50 mL), washed with water (20 mL) and brine (20 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (SiO2, DCM/methanol 1:1) followed by prep-HPLC (Table 2, Method b) to give 1-methyl-4-(2-methyl-4-methylsulfonyl-phenyl)-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine (0.015 g, 0.036 mmol, 3%) as an off white solid: LC-MS (Table 1, Method a) Rt=2.98 min; m/z 415 (M+H)+; 1H-NMR (CDCl3, Bruker 400 MHz) δ 2.65-2.73 (1H, m) 2.70 (3H, s) 2.81 (1H, ddd, J=15.0, 9.3, 2.4 Hz) 3.01 (3H, s) 3.23-3.32 (1H, m) 3.61-3.71 (1H, m) 3.84 (3H, s) 3.86 (1H, br s) 6.79 (1H, s) 7.09 (1H, ddd, J=7.4, 5.1, 1.0 Hz) 7.40 (1H, d, J=8.1 Hz) 7.58-7.64 (2H, m) 7.73 (1H, d, J=1.6 Hz) 7.86 (1H, d, J=8.0 Hz) 8.44 (1H, d, J=4.8 Hz).

1. temperatureAfter cooling to rt
2. washwashed with water (20 mL) and brine (20 mL)
3. dry with materialdried (MgSO4)
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customThe residue was purified by column chromatography (SiO2, DCM/methanol 1:1)

ORDレコード

ord-e3ee9fc77c1c4301a0c30f6262bcc2f5

出典データセット

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09150592B2