2,4-Dichlorobenzaldehyde → HCID 136348430, compound

Temperature

100 °C

A mixture of 5-amino-1,3-dimethyl-pyrazol (1.87 g, 16.8 mmol), 2,4-dichlorobenzaldehyde (2.95 g, 16.8 mmol, Fluorochem), and 2-mercapto-2-methylpropanoic acid (2.5 g, 20.8 mmol) was heated, in a microwave for about 60 min, at about 100° C. Subsequently, the reaction mixture was sealed and heated, for about 24 h, at about 150° C. After cooling to rt, THF (300 ml) was added, followed by EDC.HCl (4.25 g, 22 mmol) and DMAP (4-dimethylamino-pyridine, 0.2 g, 1.64 mmol). Subsequently, the reaction mixture was stirred for about 24 h, at rt. NaOH (2 M aqueous, 10 mL) and ethyl acetate (200 mL) were added. The layers were separated and the aqueous layer was extracted with ethyl acetate (50 mL). The combined organic layers were washed with water (2×50 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (SiO2, diethyl ether, followed by ethyl acetate) to afford 4-(2,4-dichlorophenyl)-1,3,6,6-tetramethyl-4,8-dihydropyrazolo[3,4-e][1,4]thiazepin-7-one (3.11 g, 8.4 mmol, 50%) as white solid: 1H-NMR (CDCl3, Bruker 400 MHz) δ 1.51 (3 H, s); 1.64 (3 H, s); 1.67 (3H, s); 3.78 (3H, s); 5.77 (1H, s); 7.17 (1H, dd, J=8.4, 2.0 Hz); 7.28 (1 H, d, J=8.4 Hz); 7.41 (1 H, d, J=2.0 Hz); H, m); 8.43 (1 H, bs).

1. customSubsequently, the reaction mixture was sealed
2. temperatureheated, for about 24 h, at about 150° C
3. temperatureAfter cooling to rt
4. customThe layers were separated
5. extractionthe aqueous layer was extracted with ethyl acetate (50 mL)
6. washThe combined organic layers were washed with water (2×50 mL)
7. dry with materialdried (MgSO4)
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe residue was purified by column chromatography (SiO2, diethyl ether, followed by ethyl acetate)

ORD record

ord-0b9bfa91771f40d2bd4b4a9cfbdffd42

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09150592B2