Formic Acid → HCID 86724088, compound

Temperature

50 °C

To acetic anhydride (5 mL, 53 mmol), was added formic acid (2.83 mL, 75 mmol). The resulting mixture was heated for about 15 min at about 50° C. To this mixture (after cooling to about 0° C.), was added 4-(2,4-dichlorophenyl)-1,3,6,6-tetramethyl-7,8-dihydro-4H-pyrazolo[3,4-e][1,4]thiazepine (50 mg, 0.14 mmol, Ex. D.4). The reaction mixture was stirred, for about 24 h, at rt. Subsequently, 5% aqueous sodium bicarbonate (25 mL) and ethyl acetate (50 mL) were added. The layers were separated and the organic layer was washed with water (25 mL), dried (MgSO4), filtered and concentrated in vacuo. The resulting residue was purified by column chromatography (SiO2, ethyl acetate), to afford 4-(2,4-dichlorophenyl)-1,3,6,6-tetramethyl-4,7-dihydropyrazolo[3,4-e][1,4]thiazepine-8-carbaldehyde (35 mg, 0.09 mmol, 65%), as a white solid. LC-MS (Table 1, Method a) Rt=4.53/4.71 min (rotamers), m/z 384 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 1.30 (3H, s) 1.49 (3 H, s) 1.65 (3 H, br s) 3.58-3.85 (2 H, br s) 3.73 (3 H, s) 5.48 (1 H, s) 7.11 (1 H, br s) 7.20 (1 H, br s) 7.44 (1 H, br s) 8.45 (1 H, s) (Major) 1H NMR (400 MHz, CDCl3) δ ppm 1.17 (3H, br s) 1.34 (3 H, br s) 1.93 (3 H, s) 3.41 (1 H, d, J=14.2 Hz) 3.69 (3 H, s) 3.76 (1 H, d, J=14.2 Hz) 5.54 (1 H, s) 7.12 (1 H, br s) 7.20 (1 H, br s) 7.39 (1 H, br s) 8.23 (1 H, br s) (Minor).

1. temperatureTo this mixture (after cooling to about 0° C.)
2. customThe layers were separated
3. washthe organic layer was washed with water (25 mL)
4. dry with materialdried (MgSO4)
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe resulting residue was purified by column chromatography (SiO2, ethyl acetate)

ORD record

ord-e0b09b42d54740c0bb8eb7c3765c8bc1

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09150592B2