tert-Butyl carbazate → HCID 72303809, compound

HRID 450823Notes

Reaction equation

HRID 450823 reaction equation
Cl[C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[CH:18]([C:19]([NH:21][O:22][CH2:23][C:24](O)=[O:25])=[O:20])[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11](=[O:27])[N:10]1[CH:28]1[CH2:33][CH2:32][CH2:31][CH2:30][CH:29]1[NH:34][S:35]([CH3:38])(=[O:37])=[O:36].[NH:39](C(OC(C)(C)C)=O)[NH2:40].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[ClH:69]>O.C(OCC)(=O)C.CN(C=O)C>[Cl:69][C:4]1[CH:5]=[C:6]([Cl:8])[CH:7]=[CH:2][C:3]=1[CH:9]1[CH:18]([C:19]([NH:21][O:22][CH2:23][C:24]([NH:39][NH2:40])=[O:25])=[O:20])[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11](=[O:27])[N:10]1[CH:28]1[CH2:33][CH2:32][CH2:31][CH2:30][CH:29]1[NH:34][S:35]([CH3:38])(=[O:36])=[O:37]

Participants

8

Reactant 4

HCID 70091tert-Butyl carbazateHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 72303326HCID 72303326, compound

Product 1

HCID 72303809HCID 72303809, compoundYield 68.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 591 mg of [({[(3RS,4RS)-3-(2,4-dichlorophenyl)-2-{(1SR,2SR)-2-[(methylsulfonyl)amino]cyclohexyl}-1-oxo-1,2,3,4-tetrahydroisoquinolin-4-yl]carbonyl}amino)oxy]acetic acid were added 8 ml of DMF, 200 mg of tert-butyl hydrazinecarboxylate, 205 mg of HOBt, and 388 mg of WSC hydrochloride, followed by stirring at room temperature for 3 hours. Ethyl acetate and water were added thereto to carry out a liquid separation operation. 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. 7.7 ml of dichloromethane was added thereto, followed by cooling to 0° C., and 1.2 ml of trifluoroacetic acid was added thereto, followed by stirring at room temperature for 5 hours. The residue was purified by silica gel column chromatography (eluent: chloroform-methanol) and recrystallized from ethyl acetate to obtain 417 mg of (3RS,4RS)-3-(2,4-dichlorophenyl)-N-(2-hydrazino-2-oxoethoxy)-2-{(1SR,2SR)-2-[(methylsulfonyl)amino]cyclohexyl}-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide as a white powder 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. addition7.7 ml of dichloromethane was added
  6. temperatureby cooling to 0° C.
  7. addition1.2 ml of trifluoroacetic acid was added
  8. stirringby stirring at room temperature for 5 hours
  9. customThe residue was purified by silica gel column chromatography (eluent: chloroform-methanol)
  10. customrecrystallized from ethyl acetate

Sources & evidence

ORD record
ord-03fb1366548a4825ad0e6ece5efee1a6
Source dataset
uspto-grants-2013_07
Patent number
US08486970B2

Reaction notes

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