Trifluoroacetic acid → 9-Bromo-10-fluoro-3,4,7,8-tetrahydro-[1,4]diazepino[7,1-a]isoquinoline-2,5-dione

HRID 926257Notes

Reaction equation

HRID 926257 reaction equation
[C:1]([N:4]1[CH2:13][CH2:12][C:11]2[C:6](=[CH:7][CH:8]=[C:9]([F:15])[C:10]=2[Br:14])[CH:5]1[CH2:16][C:17]([O:19]C)=O)(=[O:3])[CH3:2].C([N:24]1C=CC2C(=CC=C(F)C=2Br)C1CC(OC)=O)(=O)C.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>ClCCCl>[Br:14][C:10]1[C:9]([F:15])=[CH:8][CH:7]=[C:6]2[C:11]=1[CH2:12][CH2:13][N:4]1[C:1](=[O:3])[CH2:2][NH:24][C:17](=[O:19])[CH:16]=[C:5]12

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 86711334Methyl 2-(2-acetyl-5-bromo-6-fluoro-1,2,3,4-tetrahydroisoquinolin-1-yl)acetateHCID 86711335Methyl 2-(2-acetyl-5-bromo-6-fluoro-1,2-dihydroisoquinolin-1-yl)acetate

Product 1

HCID 867113419-Bromo-10-fluoro-3,4,7,8-tetrahydro-[1,4]diazepino[7,1-a]isoquinoline-2,5-dione

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

methyl 2-(2-acetyl-5-bromo-6-fluoro-1,2,3,4-tetrahydroisoquinolin-1-yl)acetate. A stirred solution of methyl 2-(2-acetyl-5-bromo-6-fluoro-1,2-dihydroisoquinolin-1-yl)acetate (70.6 g, 206 mmol), triethylsilane (176 g, 1517 mmol) and trifluoroacetic acid (121 mL, 1568 mmol) in 1,2-dichloroethane (500 mL) was stirred at 80° C. for 3.5 h. The reaction mixture was cooled to rt and the solvent was evaporated under reduced pressure. The remaining volatile components were evaporated under high vacuo and 40° C. bath temperature. To the resulting yellow residue saturated aqueous NaHCO3 (500 mL) was added while stirring and the mixture was extracted with DCM (3×400 mL). The organic layer was washed with saturated aqueous NaHCO3 (250 mL) and brine (200 mL). The organic layer was treated with charcoal, then dried with sodium sulfate, filtered through a pad of Hyflo and the solvent was removed under reduced pressure. The crude product was crystallized from diethyl ether (200 mL) to yield the title compound as white crystals (47.6 g). UPLC-MS: MS 344.1/346.1 (M+H+); UPLC rt 0.95 min.

Workup

  1. customthe solvent was evaporated under reduced pressure
  2. customThe remaining volatile components were evaporated under high vacuo and 40° C. bath temperature
  3. additionTo the resulting yellow residue saturated aqueous NaHCO3 (500 mL) was added
  4. extractionthe mixture was extracted with DCM (3×400 mL)
  5. washThe organic layer was washed with saturated aqueous NaHCO3 (250 mL) and brine (200 mL)
  6. additionThe organic layer was treated with charcoal
  7. dry with materialdried with sodium sulfate
  8. filtrationfiltered through a pad of Hyflo
  9. customthe solvent was removed under reduced pressure
  10. customThe crude product was crystallized from diethyl ether (200 mL)

Sources & evidence

ORD record
ord-9580ed6ee5ef415f99289df4587debe8
Source dataset
uspto-grants-2016_03
Patent number
US09284331B2

Reaction notes

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