3-Methoxybenzonitrile → 9-methoxy-2-(3-methoxyphenyl)-7,8-dihydro-[1,4]diazepino[7,1-a]isoquinolin-5(4H)-one

HRID 532906Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[CH2:5][CH2:6][NH:7][C:8]2=[CH:13]/[C:14](/[C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([O:23][CH3:24])[CH:18]=1)=[N:15]/[H].C[O:26][C:27]1C=CC=C2[C:28]=1CCN=C2C.[Li+].CC([N-]C(C)C)C.COC1C=C(C=CC=1)C#N>CCOCC>[CH3:1][O:2][C:3]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[CH2:5][CH2:6][N:7]1[C:27](=[O:26])[CH2:28][N:15]=[C:14]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([O:23][CH3:24])[CH:18]=3)[CH:13]=[C:8]12

Participants

Conditions

Temperature: -30 °C

Procedure

(Z)-2-(5-methoxy-3,4-dihydroisoquinolin-1(2H)-ylidene)-1-(3-methoxyphenyl)ethanimine. 1-1. A flask was charged with 5-methoxy-1-methyl-3,4-dihydroisoquinoline (3.0 g, 17.1 mmol) and Et2O (100 mL) under N2 and cooled to −30° C. A 2M solution of LDA (8.56 mL, 17.1 mmol) was added dropwise. The resulting brown suspension was stirred for 30 min at this temperature, and then cooled to −78° C. A solution of 3-methoxybenzonitrile (2.28 g, 17.1 mmol) in Et2O (25 mL) was added dropwise. The mixture was stirred at −78° C. for 1 h, and then allowed to warm to RT and stirred for another 18 h. the mixture was then poured onto H2O and extracted with AcOEt. The org. layers were dried over Na2SO4, filtered and concentrated in vacuo to give the title compound (5.9 g) as a brown oil that was used as it is in the next step. UPLC-MS: MS 309.3 (M+H+); UPLC rt 0.73 min.

Workup

temperaturecooled to −78° C
stirringThe mixture was stirred at −78° C. for 1 h
temperatureto warm to RT
stirringstirred for another 18 h. the mixture
additionwas then poured onto H2O
extractionextracted with AcOEt
dry with materiallayers were dried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-c16308862cae4d17a3a682c451458576
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08853203B2

Reaction notes

Loading…