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

HRID 926253Notes

Reaction equation

HRID 926253 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]([C:16](=[O:26])[CH2:17][NH:18][C:19](OC(C)(C)C)=[O:20])[CH:7]2[CH2:12]C(O)=O.BrC1C=CC=C2C=1CCN(C(=O)CNC(OC(C)(C)C)=O)C2CC(OC)=O.[OH-].[Na+]>CCO>[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:26])[CH2:17][NH:18][C:19](=[O:20])[CH:12]=[C:7]12

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 867113322-(5-Bromo-2-(2-((tert-butoxycarbonyl)amino)acetyl)-1,2,3,4-tetrahydroisoquinolin-1-yl)acetic acidHCID 89980501Methyl 2-(5-bromo-2-(2-((tert-butoxycarbonyl)amino)acetyl)-1,2,3,4-tetrahydroisoquinolin-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 702EthanolSolvent

Procedure

2-(5-bromo-2-(2-((tert-butoxycarbonyl)amino)acetyl)-1,2,3,4-tetrahydroisoquinolin-1-yl)acetic acid. To a stirred solution of methyl 2-(5-bromo-2-(2-((tert-butoxycarbonyl)amino)acetyl)-1,2,3,4-tetrahydroisoquinolin-1-yl)acetate (113 g, 257 mmol) in EtOH (1000 mL), 4N aqueous NaOH (74.5 mL, 298 mmol) was added and the solution was stirred at RT for 2 h. The white precipitate was filtered off and the white solid was washed with a small amount of EtOH (1×) and diethyl ether (2×). The sodium salt was partitioned between 0.5N aqueous HCl and DCM, the organic layer was separated and washed with 0.5N aqueous HCl (1×) and brine (1×). 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 (110 g). UPLC-MS: MS 427.2/429.2 (M+H+); UPLC rt 0.98 min.

Workup

  1. filtrationThe white precipitate was filtered off
  2. washthe white solid was washed with a small amount of EtOH (1×) and diethyl ether (2×)
  3. customThe sodium salt was partitioned between 0.5N aqueous HCl and DCM
  4. customthe organic layer was separated
  5. washwashed with 0.5N aqueous HCl (1×) and brine (1×)
  6. dry with materialThe combined organic layers were dried with sodium sulfate
  7. filtrationfiltered
  8. customthe solvent was removed under reduced pressure
  9. customThe residue was dried under high vacuo overnight

Sources & evidence

ORD record
ord-889b09d19a194c47ab40617b62563446
Source dataset
uspto-grants-2016_03
Patent number
US09284331B2

Reaction notes

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