Tri-o-tolylphosphine → (E)-N-(3-Chloro-2-propoxybenzyl)-3-(3,3-dimethyl-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)-N-methylacrylamide

A solution of N-(3-chloro-2-propoxybenzyl)-N-methylacrylamide (0.392 g, 1.47 mmol) in propionitrile (5 mL) and DMF (1 mL) was deoxygenated with Ar for 20 min. The solution was treated with diisopropylethylamine (0.40 mL, 2.33 mmol) and 7-bromo-3,3-dimethyl-1,3,4,5-tetrahydro-pyrido[2,3-e][1,4]diazepin-2-one (0.300 g, 1.11 mmol). The solution was deoxygenated with Ar for 20 min. Pd(OAc)2 (0.024 g, 0.111 mmol) and P(o-tol)3 (0.067 g, 0.222 mmol) were then added and the solution was deoxygenated again with Ar for 20 min. The mixture was heated to reflux for 18 h, then allowed to cool. The mixture was diluted with EtOAc (30 mL) and was washed with H2O (3×50 mL). The organic layer was washed with brine (1×100 mL), dried (Na2SO4) and concentrated to an orange oil. Purification by column chromatography (silica gel, CH2Cl2/MeOH, 100 to 98:2) gave the title compound (0.30 g, 59%) as a light yellow solid and as a mixture of amide rotamers: 1H NMR (300 MHz, DMSO-d6) δ 9.80-9.78 (m, 1H), 8.40-8.37 (m, 1H), 8.01-7.92 (m, 1H), 7.54-7.49 (m, 1H), 7.41-7.25 (m, 2H), 7.15-7.05 (m, 2H), 4.86-4.68 (m, 2H), 3.91-3.84 (m, 4H), 3.14-2.95 (m, 4H), 1.83-1.76 (m, 2H), 1.31-1.29 (m, 6H), 1.05-0.99 (m, 3H).

1. customThe solution was deoxygenated with Ar for 20 min
2. customthe solution was deoxygenated again with Ar for 20 min
3. temperatureThe mixture was heated
4. temperatureto reflux for 18 h
5. temperatureto cool
6. additionThe mixture was diluted with EtOAc (30 mL)
7. washwas washed with H2O (3×50 mL)
8. washThe organic layer was washed with brine (1×100 mL)
9. dry with materialdried (Na2SO4)
10. concentrationconcentrated to an orange oil
11. customPurification by column chromatography (silica gel, CH2Cl2/MeOH, 100 to 98:2)

ORD 기록

ord-d7a91475440d4429bb832d18d354aa7d

출처 데이터셋

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08450307B2