Hydrochloric Acid → Tert-butyl 1,2,4a,5,6,7-hexahydrobenzo[b]pyrazino[1,2-d][1,4]diazepine-3(4h)-carboxylate

HRID 1035279Notes

Reaction equation

O=[C:2]1[NH:8][C:7]2[CH:9]=[CH:10][CH:11]=[CH:12][C:6]=2[N:5]2[CH2:13][CH2:14][N:15]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:16][CH:4]2[CH2:3]1.B.Cl.C(=O)(O)[O-].[Na+]>O1CCCC1.ClCCl.CO>[CH2:13]1[N:5]2[C:6]3[CH:12]=[CH:11][CH:10]=[CH:9][C:7]=3[NH:8][CH2:2][CH2:3][CH:4]2[CH2:16][N:15]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:14]1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of Example 1C (1 g, 3.15 mmol) in tetrahydrofuran (10 mL) was added borane (1 M/tetrahydrofuran, 12.6 mL, 12.6 mmol). The solution was heated to 80° C. for 4 hours. Methanol (20 mL) was added, and the reaction heated at 80° C. for 1 hour. The reaction was cooled to room temperature and 1 M HCl (30 mL) was added. This solution was stirred for 30 minutes, before the solution was neutralized with sodium bicarbonate (aqueous). Dichloromethane was used to extract the product. The product was purified via flash chromatography (20-70% ethyl acetate/hexanes) to afford the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 6.77 (d, J=7.54 Hz, 1H), 6.64-6.73 (m, 1H), 6.48-6.59 (m, 2H), 5.27 (s, 1H), 3.54-3.67 (m, 1H), 3.35-3.50 (m, 2H), 3.20-3.29 (m, 1H), 2.96-3.19 (m, 4H), 2.85-2.96 (m, 1H), 1.76-1.92 (m, 1H), 1.59-1.75 (m, 1H), 1.41 (s, 9H); MS (APCI+) m/z 304.3 (M+H)+.

Workup

temperaturethe reaction heated at 80° C. for 1 hour
temperatureThe reaction was cooled to room temperature
extractionto extract the product
customThe product was purified via flash chromatography (20-70% ethyl acetate/hexanes)

Sources & evidence

ORD record: ord-62f520f733aa4b77938d477c19197ac9
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08546377B2

Reaction notes

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