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

HRID 926255Notes

Reaction equation

HRID 926255 reaction equation
[Br:1][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])[CH2:12][CH:7]12.[Cl-].BrC1C=CC=C2C=1CCN(C(=O)C[NH3+])C2CC(O)=O.C(N(CC)CC)C.Cl>C(Cl)Cl.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.CCOC(C)=O>[Br:1][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

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 867113302-(5-bromo-1-(carboxymethyl)-3,4-dihydroisoquinolin-2(1H)-yl)-2-oxoethanaminium chlorideHCID 867113339-Bromo-1,3,4,7,8,12b-hexahydro-[1,4]diazepino[7,1-a]isoquinoline-2,5-dione

Product 1

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

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 111923Propylphosphonic anhydrideSolvent

Procedure

9-bromo-1,3,4,7,8,12b-hexahydro-[1,4]diazepino[7,1-a]isoquinoline-2,5-dione. To a stirred solution of 2-(5-bromo-1-(carboxymethyl)-3,4-dihydroisoquinolin-2(1H)-yl)-2-oxoethanaminium chloride (88 g, 242 mmol) and triethylamine (169 mL, 1210 mmol) in DCM (960 mL), T3P (212 mL, 363 mmol, 50% m/m in AcOEt) was added slowly (exotherm) and the suspension was stirred at rt for 1 h. The solvent was reduced to a small amount under reduced pressure and the thick suspension was treated with 2N aqueous HCl (500 mL). The white suspension was stirred at RT for 15 min and the solid was filtered off. The solid was again treated with 2N aqueous HCl (300 mL), stirred for 10 min and filtered of. The slightly yellow solid was washed with water (1×) and with diethyl ether (2×). The resulting solid was dried at 50° C. under high vacuo overnight to yield the title compound as beige solid (71 g). UPLC-MS: MS 309.1/311.1 (M+H+); UPLC rt 0.72 min.

Workup

  1. stirringThe white suspension was stirred at RT for 15 min
  2. filtrationthe solid was filtered off
  3. additionThe solid was again treated with 2N aqueous HCl (300 mL)
  4. stirringstirred for 10 min
  5. filtrationfiltered of
  6. washThe slightly yellow solid was washed with water (1×) and with diethyl ether (2×)
  7. customThe resulting solid was dried at 50° C. under high vacuo overnight

Sources & evidence

ORD record
ord-8c997dd6cc3240279d7fd69c7fb6983f
Source dataset
uspto-grants-2016_03
Patent number
US09284331B2

Reaction notes

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