Ethyl Acetate → (3RS,4RS)-3-(2,4-dichlorophenyl)-N-{[5-(hydroxymethyl)-1,2,4-oxadiazol-3-yl]methoxy}-2-{(1SR,2 SR)-2-[(mesyl)amino]cyclohexyl}-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide

HRID 1747086Notes

Reaction equation

HRID 1747086 reaction equation
C([O:4][CH2:5][C:6]1[O:10][N:9]=[C:8]([CH2:11][O:12][NH:13][C:14]([CH:16]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[C:19](=[O:26])[N:18]([CH:27]3[CH2:32][CH2:31][CH2:30][CH2:29][CH:28]3[NH:33][S:34]([CH3:37])(=[O:36])=[O:35])[CH:17]2[C:38]2[CH:43]=[CH:42][C:41]([Cl:44])=[CH:40][C:39]=2[Cl:45])=[O:15])[N:7]=1)(=O)C.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>CO>[Cl:45][C:39]1[CH:40]=[C:41]([Cl:44])[CH:42]=[CH:43][C:38]=1[CH:17]1[CH:16]([C:14]([NH:13][O:12][CH2:11][C:8]2[N:7]=[C:6]([CH2:5][OH:4])[O:10][N:9]=2)=[O:15])[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:19](=[O:26])[N:18]1[CH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH:28]1[NH:33][S:34]([CH3:37])(=[O:36])=[O:35]

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 72303716(3-{[({[(3RS,4RS)-3-(2,4-dichlorophenyl)-2-{(1SR,2SR)-2-[(mesyl)amino]cyclohexyl}-1-oxo-1,2,3,4-tetrahydroisoquinolin-4-yl]carbonyl}amino)oxy]methyl}-1,2,4-oxadiazol-5-yl)methyl acetate

Product 1

HCID 72303442(3RS,4RS)-3-(2,4-dichlorophenyl)-N-{[5-(hydroxymethyl)-1,2,4-oxadiazol-3-yl]methoxy}-2-{(1SR,2 SR)-2-[(mesyl)amino]cyclohexyl}-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamideYield 51.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 323 mg of (3-{[({[(3RS,4RS)-3-(2,4-dichlorophenyl)-2-{(1SR,2SR)-2-[(mesyl)amino]cyclohexyl}-1-oxo-1,2,3,4-tetrahydroisoquinolin-4-yl]carbonyl}amino)oxy]methyl}-1,2,4-oxadiazol-5-yl)methyl acetate in 6.5 ml of methanol was added 66 mg of potassium carbonate, followed by stirring at room temperature for 3 hours. To the reaction solution was added ethyl acetate, followed by washing with a saturated aqueous sodium chloride solution. The organic layer was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent:chloroform-methanol) and then recrystallized from ethyl acetate to obtain 157 mg of (3RS,4RS)-3-(2,4-dichlorophenyl)-N-{[5-(hydroxymethyl)-1,2,4-oxadiazol-3-yl]methoxy}-2-{(1SR,2SR)-2-[(mesyl)amino]cyclohexyl}-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide as a white crystal.

Workup

  1. washby washing with a saturated aqueous sodium chloride solution
  2. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by silica gel column chromatography (eluent:chloroform-methanol)
  5. customrecrystallized from ethyl acetate

Sources & evidence

ORD record
ord-df74ef206d854083be6781c5a1c25a55
Source dataset
uspto-grants-2015_10
Patent number
US09150541B2

Reaction notes

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