1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 1-Oxodihydroisoquinoline-4-carboxamide

HRID 450810Notes

Reaction equation

HRID 450810 reaction equation
ClC1C=C(Cl)C=CC=1[CH:9]1[CH:18]([C:19](O)=[O:20])[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11](=[O:22])[N:10]1C1CCCCC1NS(C)(=O)=O.O1CCCCC1OC1C=C(C=CC=1)CO[NH2:46].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>O.C(OCC)(=O)C.CN(C=O)C>[O:22]=[C:11]1[C:12]2[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:18]([C:19]([NH2:46])=[O:20])[CH2:9][NH:10]1

Participants

8

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 59479025O-[3-(tetrahydro-2H-pyran-2-yl oxy)benzyl]hydroxylamineHCID 68445921(3RS,4RS)-3-(2,4-dichlorophenyl)-2-{(1SR,2SR)-2-[(mesyl)amino]cyclohexyl}-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid

Product 1

HCID 690850981-Oxodihydroisoquinoline-4-carboxamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 400 mg of (3RS,4RS)-3-(2,4-dichlorophenyl)-2-{(1SR,2SR)-2-[(mesyl)amino]cyclohexyl}-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid were added 8 ml of DMF, 243 mg of O-[3-(tetrahydro-2H-pyran-2-yl oxy)benzyl]hydroxylamine, 159 mg of HOBt, and 243 mg of WSC, followed by stifling at room temperature for 3 hours. The reaction solution was added with ethyl acetate and water to carry out a liquid separation operation, and the organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and then evaporated under reduced pressure. To the residue was added methanol, and concentrated hydrochloric acid was added dropwise thereto under ice-cooling, followed by stirring under ice-cooling for 1 hour. The precipitated crystal was collected by filtration to obtain 275 mg of (3RS,4RS)-3-(2,4-dichlorophenyl)-N-[(3-hydroxybenzyl)oxy]-2-{(1SR,2SR)-2-Rmesyl)amino]cyclohexyl}-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide as a white crystal.

Workup

  1. customa liquid separation operation
  2. washthe organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution
  3. dry with materiala saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate
  4. customevaporated under reduced pressure
  5. additionTo the residue was added methanol, and concentrated hydrochloric acid
  6. additionwas added dropwise
  7. temperatureunder ice-cooling
  8. temperaturecooling for 1 hour
  9. filtrationThe precipitated crystal was collected by filtration

Sources & evidence

ORD record
ord-40d56f65b2ec4e88908c2a3c93e7919c
Source dataset
uspto-grants-2013_07
Patent number
US08486970B2

Reaction notes

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