Ammonium Chloride → 9-(Tert-butyl)-3,4,7,8-tetrahydro-[1,4]diazepino[7,1-a]isoquinoline-2,5-dione

HRID 926332Notes

Reaction equation

Br[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.F[B-](F)(F)F.[CH:24]1([C:30]2NC=C[N+]=2C2CCCCC2)[CH2:29]CCC[CH2:25]1.C([Mg]Cl)(C)(C)C.[NH4+].[Cl-]>C1COCC1.Cl[Ni]Cl>[C: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)([CH3:30])([CH3:29])[CH3:25]

Participants

Conditions

Temperature: -20 °C

Procedure

125-1. A mixture of 9-bromo-3,4,7,8-tetrahydro-[1,4]diazepino[7,1-a]isoquinoline-2,5-dione (2.0 g, 6.51 mmol), NiCl2*2H2O (0.43 g, 2.60 mmol) and dicyclohexylimidazolium tetrafluoroborate (0.83 g, 2.60 mmol) in THF (80 mL) was cooled to −20° C. and then treated with a 1M solution of tBuMgCl (39.0 mL, 39.0 mmol) dropwise. The mixture was allowed to slowly warm to RT, then poured onto a saturated aq. solution of NH4Cl and extracted with AcOEt. The combined org. layers were then dried over Na2SO4, filtered and concentrated in vacuo. Purification by flash chromatography (SiO2, heptane to AcOEt to AcOEt/MeOH 95:5) afforded the title compound (370 mg). UPLC-MS: MS 285.2 (M+H+); UPLC rt 0.91 min.

Workup

temperatureto slowly warm to RT
extractionextracted with AcOEt
dry with materiallayers were then dried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customPurification by flash chromatography (SiO2, heptane to AcOEt to AcOEt/MeOH 95:5)

Sources & evidence

ORD record: ord-6cd95bf040c94b6191699534645143f4
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09284331B2

Reaction notes

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