Triethylamine → 9-Iodo-3,4,7,8-tetrahydro-[1,4]diazepino[7,1-a]isoquinoline-2,5-dione

HRID 926248Notes

Reaction equation

HRID 926248 reaction equation
[I: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-].C(CC1C2C(=C(I)C=CC=2)CCN1C(=O)C[NH3+])(O)=O.CCN(CC)CC.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>CN(C=O)C.CCOC(C)=O.C([O-])(O)=O.[Na+].CO>[I: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

9

Reactant 4

HCID 8471TriethylamineHCID 111923Propylphosphonic anhydrideHCID 867113252-(1-(carboxymethyl)-5-iodo-3,4-dihydroisoquinolin-2(1H)-yl)-2-oxoethanaminium chlorideHCID 86711327HCID 86711327, compound

Product 1

HCID 867113799-Iodo-3,4,7,8-tetrahydro-[1,4]diazepino[7,1-a]isoquinoline-2,5-dione

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

9-iodo-1,3,4,7,8,12b-hexahydro-[1,4]diazepino[7,1-a]isoquinoline-2,5-dione. A suspension of 2-(1-(carboxymethyl)-5-iodo-3,4-dihydroisoquinolin-2(1H)-yl)-2-oxoethanaminium chloride (46.1 g, 112 mmol) and Et3N (95 mL, 682 mmol) in dry DMF (1.1 L) was treated with a solution of T3P in DMF (98 mL, 169 mmol) exothermic. The mixture was stirred at RT overnight. The mixture was then concentrated in vacuo and the residue obtained was taken up in AcOEt and diluted with an saturated aq. solution of NaHCO3. The aqueous phase was extracted with AcOEt and the combined org. layers were then washed with brine, dried over Na2SO4, filtered and concentrated in vacuo to give a brown solid. The crude product obtained was suspended in MeOH and filtered. The filter cake was washed with MeOH and DCM, and then dried in vacuo to give the title compound (12.4 g) as a beige powder that was used as it is in the next step. UPLC-MS: MS 357.1 (M+H+); UPLC rt 0.73 min.

Workup

  1. concentrationThe mixture was then concentrated in vacuo
  2. customthe residue obtained
  3. extractionThe aqueous phase was extracted with AcOEt
  4. washlayers were then washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give a brown solid
  9. customThe crude product obtained
  10. filtrationfiltered
  11. washThe filter cake was washed with MeOH and DCM
  12. customdried in vacuo

Sources & evidence

ORD record
ord-5832cf4d4b8c41c79132a60f9f6cb73a
Source dataset
uspto-grants-2016_03
Patent number
US09284331B2

Reaction notes

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