1-(2-Aminophenyl)-4-chloro-1-butanone → HCID 178478460, compound

To a suspension of 1-(2-aminophenyl)-4-chloro-1-butanone (508 mg, 2.6 mmol) in concentrated HCl (3.5 mL) at −5° C. was added a solution of NaNO2 (193 mg, 2.8 mmol) in H2O (0.75 mL), and the reaction mixture was stirred for 1 h. A solution of SnCl2-2H2O (1.37 g, 6.07 mmol) in concentrated HCl (1.9 mL) was added at −5° C. to the solution, and this stirred for 1 h under ice cooling. The reaction was quenched with H2O and extracted into Et2O (100 mL). The organic solution was washed with H2O (50 mL) and brine (50 mL), dried over MgSO4 and concentrated in vacuo. Purification by column chromatography afforded 3-(3-chloropropyl)-1H-indazole (126 mg, 25%) as a yellow solid. The title compound was isolated as a yellow oil (38 mg, 77%) according to the method of Example 286, Step C from (8aS,12aR)-6,7,8a,9,10,11,12,12a-octahydro-5H-pyrido[4,3-b][1,4]thiazepino[2,3,4-hi]indole (30 mg, 0.12 mmol) and 3-(3-chloropropyl)-1H-indazole (44 mg, 0.24 mmol). 1H NMR (CDCl3) δ1.83-2.19 (m, 7H), 2.23-2.35 (m, 1H), 2.43-2.54 (m, 2H), 2.72-2.79 (m, 1H), 2.81-2.88 (m, 1H), 2.92-3.11 (m, 4H), 3.12-3.21 (m, 1H), 3.24-3.29 (m, 1H), 3.51-3.62 (m, 1H), 3.80-3.92 (m, 1H), 6.61 (t, 1H, J=7.5 Hz), 6.84 (d, 1H, J=6.6 Hz), 6.94 (dd, 1H, J=1.1, 7.7 Hz), 7.11-7.16 (m, 1H), 7.34-7.48 (m, 2H), 7.70 (d, 1H, J=8.0 Hz) ppm.

1. stirringthis stirred for 1 h under ice cooling
2. customThe reaction was quenched with H2O
3. extractionextracted into Et2O (100 mL)
4. washThe organic solution was washed with H2O (50 mL) and brine (50 mL)
5. dry with materialdried over MgSO4
6. concentrationconcentrated in vacuo
7. customPurification by column chromatography

ORD record

ord-616c6bc2f8b6473b812eb45a255c3400

Source dataset

uspto-grants-2004_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06713471B1