Acetonitrile → 3-Amino-7-(2-chlorophenyl)-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-2-carbonitrile

MeCN (10 mL) was added to a solution of NaHMDS (100 mL, 1.0M in THF, 100 mmol) in THF (50 mL) at −78° C. to give a thick white precipitate. 2-Chlorophenyl isothiocyanate (7.72 g, 45.45 mmol) was added to give a brown solution. The mixture was allowed to warm to r.t. over 1 h then diluted with EtOH (50 mL). N,N-Dimethyluracil (6.4 g, 45 mmol) was added and the mixture heated at reflux for 24 h. Volatiles were removed in vacuo and the residue dissolved in MeCN (100 mL). Chloroacetonitrile (2.85 mL, 45 mmol) was added and the mixture heated at 50° C. for 1 h, a second charge of chloroacetonitrile (2.85 mL, 45 mmol) was added and heating continued for 1.5 h. Some of the MeCN (˜50 mL) was removed in vacuo and H2O was added to precipitate the product. The brown solid was filtered off, washed with H2O (50 mL) and Et2O (50 mL) and dried to give the title compound as a brown solid (14.3 g, quant.). δH (DMSO-d6) 8.10 (1H, d, J 9.7 Hz), 7.75-7.73 (1H, m), 7.65-7.54 (3H, m), 7.14 (2H, br s, NH2), 6.54 (1H, d, J 9.7 Hz). LCMS (ES+) RT 2.97 minutes, 302 (M+H)+.

1. customto give a thick white precipitate
2. customto give a brown solution
3. temperaturethe mixture heated
4. temperatureat reflux for 24 h
5. customVolatiles were removed in vacuo
6. dissolutionthe residue dissolved in MeCN (100 mL)
7. temperaturethe mixture heated at 50° C. for 1 h
8. additionwas added
9. temperatureheating
10. customSome of the MeCN (˜50 mL) was removed in vacuo and H2O
11. additionwas added
12. customto precipitate the product
13. filtrationThe brown solid was filtered off
14. washwashed with H2O (50 mL) and Et2O (50 mL)
15. customdried

ORDレコード

ord-93fce16d42bf4fe283404a647d5a61a1

出典データセット

uspto-grants-2009_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07482452B2