Hydrochloric Acid → 2-(4-tert-butoxycarbonylbenzyl)-6-dimethylcarbamoyl-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxylic Acid Methyl Ester

HRID 750258Notes

Reaction equation

HRID 750258 reaction equation
[CH3:1][O:2][C:3]([C:5]1[N:6]([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])=[CH:28][CH:27]=2)[C:7](=[O:24])[C:8]2[C:13]([C:14]=1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[CH:12][C:11]([C:21]([OH:23])=O)=[CH:10][CH:9]=2)=[O:4].[Cl-].C[NH3+].Cl.[CH2:43]([N:45]=[C:46]=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1.Cl>C1COCC1.O.C(N(CC)CC)C>[CH3:1][O:2][C:3]([C:5]1[N:6]([CH2:25][C:26]2[CH:27]=[CH:28][C:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])=[CH:30][CH:31]=2)[C:7](=[O:24])[C:8]2[C:13]([C:14]=1[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)=[CH:12][C:11]([C:21](=[O:23])[N:45]([CH3:46])[CH3:43])=[CH:10][CH:9]=2)=[O:4]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 11637Methanamine, hydrochloride (1:1)HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 691566122-(4-tert-butoxycarbonylbenzyl)-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3,6-dicarboxylic Acid 3-methyl Ester

Product 1

HCID 691567922-(4-tert-butoxycarbonylbenzyl)-6-dimethylcarbamoyl-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carboxylic Acid Methyl EsterYield 50.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of 2-(4-tert-butoxycarbonylbenzyl)-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3,6-dicarboxylic acid 3-methyl ester (300 mg) in THF (6 ml) were added methyl ammonium chloride (150 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (230 mg), 1-hydroxy-1H-benzotriazole monohydrate (180 mg) and triethylamine (1 ml) at room temperature. The reaction mixture was stirred at 40° C. for 12 hrs. Water and 1N-hydrochloric acid were added to acidify the aqueous layer and the mixture was extracted with ethyl acetate. The organic layer was washed with water, saturated aqueous sodium hydrogen carbonate solution, water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was crystallized from methanol to give the title compound (160 mg).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with water, saturated aqueous sodium hydrogen carbonate solution, water and saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. customthe obtained residue was crystallized from methanol

Sources & evidence

ORD record
ord-68c381e626cf4d3abedf78cffd75543a
Source dataset
uspto-grants-2008_07
Patent number
US07402595B2

Reaction notes

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