反应详情

温度

90 °C

3-(hydroxymethyl)-7a,8,9,10-tetrahydro-5H-pyrido[3,2-b]pyrrolo[1,2-d][1,4]diazepin-6(7H)-one (100 mg, 0.429 mmol), 4-(piperazin-1-yl)benzonitrile (96 mg, 0.514 mmol), (cyanomethyl)trimethylphosphonium iodide (167 mg, 0.685 mmol) and N,N-diisopropylethylamine (0.374 mL, 2.141 mmol) were suspended in propiononitrile (Volume: 2 mL) and heated in a closed vial at 90° C. for 5 h. The reaction mixture was cooled, diluted with DMSO (2 mL) and purified using preparative HPLC (basic phase, 25-95% ACN). The fractions containing product were concentrated in vacuo and crystallized from water (5 mL). The precipitate was filtered and dried in vacuum to afford 4-(4-((6-oxo-6,7,7a,8,9,10-hexahydro-5H-pyrido[3,2-b]pyrrolo[1,2-d][1,4]diazepin-3-yl)methyl)piperazin-1-yl)benzonitrile (124.2 mg, 0.309 mmol, 72.1% yield) as a light brown solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.51-1.65 (m, 1H) 1.72-1.86 (m, 1H) 1.87-1.97 (m, 1H) 2.14 (qd, J=5.81, 4.04 Hz, 1H) 2.40-2.48 (m, 4H) 2.52-2.59 (m, 1H) 2.66 (dd, 1H) 3.30 (br. s., 4H) 3.33-3.40 (m, 2H) 3.45-3.54 (m, 1H) 3.66 (td, J=10.61, 6.82 Hz, 1H) 3.88 (td, J=9.47, 6.06 Hz, 1H) 7.00 (d, J=9.35 Hz, 2H) 7.14 (d, J=2.02 Hz, 1H) 7.57 (d, J=9.09 Hz, 2H) 7.75 (d, J=2.02 Hz, 1H) 9.56 (d, 1H). [M+H] calc'd for C23H26N6O, 402. found, 402.

1. temperatureThe reaction mixture was cooled
2. custompurified
3. additionThe fractions containing product
4. concentrationwere concentrated in vacuo
5. customcrystallized from water (5 mL)
6. filtrationThe precipitate was filtered
7. customdried in vacuum