Pyrazole → HCID 68445749, compound

HRID 1747073Notes

Reaction equation

HRID 1747073 reaction equation
Cl[CH2:2][CH2:3][NH:4][C:5]([CH:7]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10](=[O:17])[N:9]([CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH:19]2[NH:24][S:25]([CH3:28])(=[O:27])=[O:26])[CH:8]1[C:29]1[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][C:30]=1[Cl:36])=[O:6].[I-].[Na+].[NH:39]1[CH:43]=[CH:42][CH:41]=[N:40]1.C(OCC)(=O)C>CN(C=O)C.O>[Cl:36][C:30]1[CH:31]=[C:32]([Cl:35])[CH:33]=[CH:34][C:29]=1[CH:8]1[CH:7]([C:5]([NH:4][CH2:3][CH2:2][N:39]2[CH:43]=[CH:42][CH:41]=[N:40]2)=[O:6])[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10](=[O:17])[N:9]1[CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][CH:19]1[NH:24][S:25]([CH3:28])(=[O:27])=[O:26]

Participants

7

Reactant 4

HCID 1048PyrazoleHCID 5238Sodium IodideHCID 8857Ethyl AcetateHCID 68450795HCID 68450795, compound

Product 1

HCID 68445749HCID 68445749, compoundYield 29.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 573 mg of (3RS,4RS)—N-(2-chloroethyl)-3-(2,4-dichlorophenyl)-2-{(1SR,2SR)-2-[(methylsulfonyl)amino]cyclohexyl}-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide in 10 ml of DMF were added 150 mg of sodium iodide and 340 mg of 1H-pyrazole, followed by stirring at 100° C. for 24 hours. Ethyl acetate and water were added thereto to carry out a liquid separation operation, and the organic layer was washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent:chloroform-methanol) to obtain a colorless crystal. The crystal was recrystallized from ethanol to obtain 176 mg of (3RS,4RS)-3-(2,4-dichlorophenyl)-2-{(1SR,2SR)-2-[(methylsulfonyl)amino]cyclohexyl}-1-oxo-N-[2-(1H-pyrazol-1-yl)ethyl]-1,2,3,4-tetrahydroisoquinoline-4-carboxamide as a colorless powdered crystal.

Workup

  1. customa liquid separation operation
  2. washthe organic layer was washed with a saturated aqueous sodium chloride solution
  3. dry with materialdried over anhydrous sodium sulfate
  4. customevaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (eluent:chloroform-methanol)
  6. customto obtain a colorless crystal
  7. customThe crystal was recrystallized from ethanol

Sources & evidence

ORD record
ord-48730d80334b491c8ff15db13d5eb182
Source dataset
uspto-grants-2015_10
Patent number
US09150541B2

Reaction notes

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