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

HRID 532872Notes

Reaction equation

HRID 532872 reaction equation
C(OC([NH:8][CH2:9][C:10]([N:12]1[CH2:21][CH2:20][C:19]2[C:14](=[CH:15][CH:16]=[CH:17][C:18]=2[I:22])[CH:13]1[CH2:23][C:24]([O:26]CC)=O)=[O:11])=O)(C)(C)C.IC1C=CC=C2C=1CCNC2CC(OCC)=O.N(C(OC(C)(C)C)=O)CC(O)=O.CCN(CC)CC.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.CN(C=O)C.C([O-])(O)=O.[Na+]>CCOC(C)=O.O>[I:22][C:18]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:19]=1[CH2:20][CH2:21][N:12]1[C:10](=[O:11])[CH2:9][NH:8][C:24](=[O:26])[CH:23]=[C:13]12

Participants

10

Reactant 7

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 78288N-(tert-butoxycarbonyl)glycineHCID 111923Propylphosphonic anhydrideHCID 516892Sodium BicarbonateHCID 86711321Ethyl 2-(5-iodo-1,2,3,4-tetrahydroisoquinolin-1-yl)acetateHCID 86711324Ethyl 2-(2-(2-((tert-butoxycarbonyl)amino)acetyl)-5-iodo-1,2,3,4-tetrahydroisoquinolin-1-yl)acetate

Product 1

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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

ethyl 2-(2-(2-((tert-butoxycarbonyl)amino)acetyl)-5-iodo-1,2,3,4-tetrahydroisoquinolin-1-yl)acetate. A mixture of ethyl 2-(5-iodo-1,2,3,4-tetrahydroisoquinolin-1-yl)acetate (39.5 g, 114 mmol), Boc-Gly-OH (20.1 g, 114 mmol) and Et3N (32 mL, 230 mmol) in AcOEt (570 mL) was treated with a solution of T3P in DMF (80 mL, 137 mmol)—exothermic. The mixture was stirred at RT for 15 h and H2O (200 mL) was then added. The pH was adjusted to 8 by addition of saturated aq. solution of NaHCO3, and the aq. phase was extracted with AcOEt. The combined org. phases were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo to give the title compound (57.4 g) that was used as it is in the next step. UPLC-MS: MS 503.2 (M+H+); UPLC rt 1.20 min.

Workup

  1. extractionthe aq. phase was extracted with AcOEt
  2. washphases were washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-dd4cafbb165f4a0b871d31fc14388a9d
Source dataset
uspto-grants-2014_10
Patent number
US08853203B2

Reaction notes

Loading…