Hydrochloric Acid → HCID 178522242, compound

HRID 660132Notes

Reaction equation

HRID 660132 reaction equation
[NH:1]([C:3](=[O:25])[C:4]([NH:6][C:7]1[CH:24]=[CH:23][C:10]([O:11][C@@H:12]2[CH2:17][CH2:16][C@H:15]([C:18]([O:20]CC)=[O:19])[CH2:14][CH2:13]2)=[CH:9][CH:8]=1)=[O:5])[NH2:2].[F:26][C:27]1[CH:28]=[C:29]([N:34]=[C:35]=S)[CH:30]=[CH:31][C:32]=1[F:33].CCN=C=NCCCN(C)C.[OH-].[Na+].Cl>CN(C=O)C.CO.C1COCC1.O>[F:26][C:27]1[CH:28]=[C:29]([NH:34][C:35]2[O:25][C:3]([C:4]([NH:6][C:7]3[CH:8]=[CH:9][C:10]([O:11][C@@H:12]4[CH2:13][CH2:14][C@H:15]([C:18]([OH:20])=[O:19])[CH2:16][CH2:17]4)=[CH:23][CH:24]=3)=[O:5])=[N:1][N:2]=2)[CH:30]=[CH:31][C:32]=1[F:33]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 27583313,4-Difluorophenyl IsothiocyanateHCID 178472469HCID 178472469, compound2×

Product 1

HCID 178522242HCID 178522242, compoundYield 47%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

Ethyl cis-4-(4-{[hydrazino(oxo)acetyl]amino}phenoxy)cyclohexanecarboxylate (Intermediate 1, 698 mg, 2.00 mmol) was added in one portion to a stirred solution of 3,4-difluorophenyl isothiocyanate (411 mg, 2.40 mmol) in DMF (10 mL) and the reaction mixture was stirred at 65° C. for 30 mins. EDCI (461 mg, 2.40 mmol) was added in one portion and the reaction mixture was heated to 85° C. for 3 h. The mixture was cooled to ambient temperature and water (15 mL) was added and the resulting suspension was filtered to leave a cream solid. The solid was taken up in a mixture of MeOH (8 mL) and THF (4 mL) and a 2N aqueous solution of NaOH (4 mL) was added in one portion and the reaction mixture was stirred at ambient temperature for 16 h. The reaction mixture was acidified by the addition of 2M HCl and the resulting precipitate was filtered, washed with water (10 mL) and dried under high vacuum to leave a solid. The solid was recrystallised from refluxing glacial acetic acid to give the title compound as a white solid (428 mg, 47%).

Workup

  1. temperaturethe reaction mixture was heated to 85° C. for 3 h
  2. temperatureThe mixture was cooled to ambient temperature
  3. filtrationthe resulting suspension was filtered
  4. customto leave a cream solid
  5. stirringthe reaction mixture was stirred at ambient temperature for 16 h
  6. filtrationthe resulting precipitate was filtered
  7. washwashed with water (10 mL)
  8. customdried under high vacuum
  9. customto leave a solid
  10. customThe solid was recrystallised
  11. temperaturefrom refluxing glacial acetic acid

Sources & evidence

ORD record
ord-ac24954286314df8b8fbdb56376be4e3
Source dataset
uspto-grants-2011_12
Patent number
US08084478B2

Reaction notes

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