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

온도

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 기록

ord-e3ee9fc77c1c4301a0c30f6262bcc2f5

출처 데이터셋

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09150592B2