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

HRID 532876Notes

Reaction equation

HRID 532876 reaction equation
[C:1]([N:4]1[CH:13]=[CH:12][C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[Br:14])[CH:5]1[CH2:15][C:16]([O:18]C)=O)(=[O:3])[CH3:2].BrC1C=CC=C2C=1C=C[N:25]=C2.C([Si](OC(OC)=C)(C)C)(C)(C)C.Cl>C(Cl)Cl>[Br:14][C:10]1[CH:9]=[CH:8][CH:7]=[C:6]2[C:11]=1[CH2:12][CH2:13][N:4]1[C:1](=[O:3])[CH2:2][NH:25][C:16](=[O:18])[CH:15]=[C:5]12

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 7364875-BromoisoquinolineHCID 45644911-(tert-Butyldimethylsilyloxy)-1-methoxyetheneHCID 89979853Methyl 2-(2-acetyl-5-bromo-1,2-dihydroisoquinolin-1-yl)acetate

Product 1

HCID 867113289-Bromo-3,4,7,8-tetrahydro-[1,4]diazepino[7,1-a]isoquinoline-2,5-dione

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

methyl 2-(2-acetyl-5-bromo-1,2-dihydroisoquinolin-1-yl)acetate. To a stirred solution of 5-bromoisoquinoline (100 g, 481 mmol) in DCM (1900 mL) acetyl chloride (35.9 mL, 505 mmol) was dropped at RT and the solution was stirred for 60 min. The solution was cooled to −78° C. (yellow suspension) and then a solution of tert-butyl((1-methoxyvinyl)oxy)dimethylsilane (95 g, 505 mmol) in DCM (500 mL) was added in one portion. The resulting yellow solution was stirred at −78° C. for 1 h and then allowed to warm to rt overnight. 2N aqueous HCl (400 mL) was added and the reaction mixture was stirred for 10 min. The organic layer was separated and washed with brine (2×). The combined organic layers were dried with sodium sulfate, filtered and the solvent was removed under reduced pressure. The residue was dissolved in diethyl ether (1000 mL), charcoal was added and the mixture was filtrated through a pad of celite. The solvent was evaporated and the crude product was dried under high vacuo overnight to yield the title compound (147 g) which was used without further purification. UPLC-MS: MS 324.0/326.0 (M+H+); UPLC rt 1.03 min.

Workup

  1. stirringThe resulting yellow solution was stirred at −78° C. for 1 h
  2. temperatureto warm to rt overnight
  3. stirringthe reaction mixture was stirred for 10 min
  4. customThe organic layer was separated
  5. washwashed with brine (2×)
  6. dry with materialThe combined organic layers were dried with sodium sulfate
  7. filtrationfiltered
  8. customthe solvent was removed under reduced pressure
  9. dissolutionThe residue was dissolved in diethyl ether (1000 mL)
  10. additioncharcoal was added
  11. filtrationthe mixture was filtrated through a pad of celite
  12. customThe solvent was evaporated
  13. dry with materialthe crude product was dried under high vacuo overnight

Sources & evidence

ORD record
ord-edb391fe0546469f9385a1ce0816dde1
Source dataset
uspto-grants-2014_10
Patent number
US08853203B2

Reaction notes

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