Hydrochloric Acid → 9-Bromo-3,4,7,8-tetrahydro-[1,4]diazepino[7,1-a]isoquinoline-2,5-dione

methyl 2-(5-bromo-2-(2-((tert-butoxycarbonyl)amino)acetyl)-1,2,3,4-tetrahydroisoquinolin-1-yl)acetate. To a stirred solution of methyl 2-(5-bromo-1,2,3,4-tetrahydroisoquinolin-1-yl)acetate (76 g, 267 mmol), Boc-glycine (51.5 g, 294 mmol) and triethylamine (74.6 mL, 535 mmol) in AcOEt (1350 mL), T3P (191 mL, 321 mmol, 50% m/m in AcOEt) was added and the solution was stirred at RT for 90 min. 0.2N aqueous HCl (400 mL) was added and the reaction mixture was stirred for 5 min. The organic layer was separated and washed with 0.2 N aqueous HCl (1×250 mL), saturated aqueous NaHCO3 (2×250 mL) and brine (1×250 mL). The combined organic layers were dried with sodium sulfate, filtered and the solvent was removed under reduced pressure. The residue was dried under high vacuo overnight to yield the title compound as white foam (113 g) which was used without further purification. UPLC-MS: MS 441.2/443.2 (M+H+); UPLC rt 1.12 min.

1. stirringthe reaction mixture was stirred for 5 min
2. customThe organic layer was separated
3. washwashed with 0.2 N aqueous HCl (1×250 mL), saturated aqueous NaHCO3 (2×250 mL) and brine (1×250 mL)
4. dry with materialThe combined organic layers were dried with sodium sulfate
5. filtrationfiltered
6. customthe solvent was removed under reduced pressure
7. customThe residue was dried under high vacuo overnight

ORD-Eintrag

ord-3626f7414df44cd7bdf87cf425f37b35

Quelldatensatz

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09284331B2