Propanal → 9-(1-Hydroxypropyl)-3,4,7,8-tetrahydro-[1,4]diazepino[7,1-a]isoquinoline-2,5-dione

HRID 532956Notes

Reaction equation

I[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][N:6]1[C:16](=[O:17])[CH2:15][NH:14][C:13](=[O:18])[CH:12]=[C:7]12.C([Mg]Cl)(C)C.[CH:24](=[O:27])[CH2:25][CH3:26]>C1COCC1>[OH:27][CH:24]([C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][N:6]1[C:16](=[O:17])[CH2:15][NH:14][C:13](=[O:18])[CH:12]=[C:7]12)[CH2:25][CH3:26]

Participants

Conditions

Temperature: -78 °C

Procedure

124-1. A mixture of 9-iodo-3,4,7,8-tetrahydro-[1,4]diazepino[7,1-a]isoquinoline-2,5-dione (2.2 g, 6.21 mmol) in dry THF (150 mL) was cooled to −78° C. under Ar, and a 2M solution of iPrMgCl in THF (18.6 mL, 37.3 mmol) was added dropwise. The mixture was stirred at −78° C. for 30 min and propionaldehyde (3.61 g, 62.1 mmol) was then added. The mixture was stirred at −78° C. for another 30 min and then allowed to warm to RT overnight. The reaction mixture was poured onto a saturated aq. solution of WWI and extracted with AcOEt. The combined org. layers were then dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by flash chromatography (SiO2, heptane to AcOEt/MeOH 9:1) to give the title compound (231 mg). UPLC-MS: MS 287.2 (M+H+); UPLC rt 0.59 min.

Workup

stirringThe mixture was stirred at −78° C. for another 30 min
temperatureto warm to RT overnight
additionThe reaction mixture was poured onto a saturated aq. solution of WWI
extractionextracted with AcOEt
dry with materiallayers were then dried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customThe crude product was purified by flash chromatography (SiO2, heptane to AcOEt/MeOH 9:1)

Sources & evidence

ORD record: ord-f405c8bde4884f48bd8ecfd0ff7fa453
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08853203B2

Reaction notes

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