Aluminium lithium hydride → HCID 59332834, compound

A suspension of 7-bromo-1,3,4,5-tetrahydro-pyrido[2,3-e][1,4]diazepin-2-one hydrochloride (1.16 g, 4.16 mmol) in THF (35 mL) was cooled in an ice bath and treated dropwise with LiAlH4 (8.4 mL of a 1.0 M solution in THF, 8.4 mmol). After stirring for 30 min, the ice bath was removed and the solution was allowed to warm to room temperature. After heating to reflux overnight, the mixture was cooled in an ice bath. The reaction was quenched sequentially with H2O (0.3 mL), 15% NaOH (0.3 mL) and H2O (0.9 mL). After 5 min, the ice bath was removed and the mixture was stirred at room temperature for 2.5 h. The mixture was filtered through Celite, and the filtrate was concentrated in vacuo to give a yellow syrup. Purification by flash column chromatography (silica gel, CH2Cl2/MeOH, 95:5 to 90:10) gave the title compound (0.42 g, 44%) as a white solid: 1H NMR (300 MHz, CDCl3) δ 8.03 (d, J=2.3 Hz, 1H), 7.44 (d, J=2.0 Hz, 1H), 4.96 (br s, 1H), 3.82 (s, 2H), 3.22-3.15 (m, 2H), 3.08-3.05 (m, 2H), 1.97 (br s, 1H); MS (ESI) m/e 228 (M+H)+.

1. temperaturewas cooled in an ice bath
2. customthe ice bath was removed
3. temperatureAfter heating
4. temperatureto reflux overnight
5. temperaturethe mixture was cooled in an ice bath
6. customThe reaction was quenched sequentially with H2O (0.3 mL), 15% NaOH (0.3 mL) and H2O (0.9 mL)
7. waitAfter 5 min
8. customthe ice bath was removed
9. stirringthe mixture was stirred at room temperature for 2.5 h
10. filtrationThe mixture was filtered through Celite
11. concentrationthe filtrate was concentrated in vacuo
12. customto give a yellow syrup
13. customPurification by flash column chromatography (silica gel, CH2Cl2/MeOH, 95:5 to 90:10)

ORD record

ord-6baca67f9055430b941099536e8dc14c

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08318720B2