Dimethylformamide → HCID 178465570, compound

HRID 450801Notes

Reaction equation

HRID 450801 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][CH2:5][CH2:4][CH:3]1[N:8]1[CH:17]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=2[Cl:25])[CH:16]([C:26]([NH:28][O:29][CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)=[O:27])[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]1=[O:37].CN(C=O)C.C(=O)([O-])[O-].[Na+].[Na+].Cl.[C:50](SC)(=[NH:52])[CH3:51]>O>[CH2:30]([O:29][NH:28][C:26]([CH:16]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9](=[O:37])[N:8]([CH:3]2[CH2:4][CH2:5][CH2:6][CH2:7][CH:2]2[NH:1][C:50](=[NH:52])[CH3:51])[CH:17]1[C:18]1[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=1[Cl:25])=[O:27])[C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium Carbonate2×HCID 20191366HCID 20191366, compound2×HCID 72303218HCID 72303218, compound

Product 1

HCID 178465570HCID 178465570, compoundYield 39%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

To a mixed liquid of 269 mg of (3RS,4RS)-2-[(1SR,2SR)-2-aminocyclohexyl]-N-(benzyloxy)-3-(2,4-dichlorophenyl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide and 5 ml of DMF were added 58 mg of sodium carbonate and 119 mg of methyl ethanimidothioate hydrochloride, followed by stirring at 60° C. for 1 hour. Thereafter, while stirring at 60° C., 233 mg of sodium carbonate and 478 mg of methyl ethanimidothioate hydrochloride were further added in four divided portions every 1 hour. After cooling the reaction solution, water was added thereto, followed by extraction with chloroform-isopropyl alcohol (5:1). The organic layer was dried over anhydrous magnesium sulfate and then concentrated. The residue was purified by silica gel column chromatography (eluent: chloroform-methanol-aqueous ammonia) and then crystallized with ethyl acetate to obtain 113 mg of (3RS,4RS)—N-(benzyloxy)-3-(2,4-dichlorophenyl)-2-[(1SR,2SR)-2-(ethanimidoylamino)cyclohexyl]-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide as a white crystal.

Workup

  1. stirringThereafter, while stirring at 60° C.
  2. additionwas added
  3. extractionfollowed by extraction with chloroform-isopropyl alcohol (5:1)
  4. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel column chromatography (eluent: chloroform-methanol-aqueous ammonia)
  7. customcrystallized with ethyl acetate

Sources & evidence

ORD record
ord-631707ccb0d647a794acebbf596e951f
Source dataset
uspto-grants-2013_07
Patent number
US08486970B2

Reaction notes

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