1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 178472467, compound

HRID 1713785Notes

Reaction equation

HRID 1713785 reaction equation
O.[NH2:2][NH2:3].[CH3:4][O:5][C:6](=O)[C:7]([NH:9][C:10]1[CH:27]=[CH:26][C:13]([O:14][C@@H:15]2[CH2:20][CH2:19][C@H:18]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:17][CH2:16]2)=[CH:12][CH:11]=1)=[O:8].[F:29][C:30]1[CH:35]=[C:34]([F:36])[C:33]([F:37])=[CH:32][C:31]=1[N:38]=C=S.CCN=C=NCCCN(C)C>CCO.CC(N(C)C)=O.O.C(OCC)C>[F:29][C:30]1[CH:35]=[C:34]([F:36])[C:33]([F:37])=[CH:32][C:31]=1[NH:38][C:4]1[O:5][C:6]([C:7]([NH:9][C:10]2[CH:27]=[CH:26][C:13]([O:14][C@@H:15]3[CH2:20][CH2:19][C@H:18]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:17][CH2:16]3)=[CH:12][CH:11]=2)=[O:8])=[N:3][N:2]=1

Participants

9

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 24654Hydrazine hydrate (1:1)2×HCID 27607942,4,5-TrifluorophenylisothiocyanateHCID 178472471HCID 178472471, compound2×

Product 1

HCID 178472467HCID 178472467, compoundYield 81.1%

Reagents, catalysts & solvents 4

HCID 702EthanolSolvent2×HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 31374DimethylacetamideSolvent2×

Procedure

Hydrazine monohydrate (32 μL, 0.65 mmol) was added in one portion to a stirred solution of ethyl cis-4-(4-{[methoxy(oxo)acetyl]amino}phenoxy)cyclohexanecarboxylate (Intermediate 108) (188 mg, 0.54 mmol) in EtOH (3 mL) and the reaction mixture was stirred at room temperature for 10 mins. EtOH (40 mL) and hydrazine monohydrate (9.0 μL, 0.18 mmol) were added and the reaction mixture was stirred for a further 20 mins. Diethylether (50 mL) was added and the mixture was filtered to leave a solid. The filtrate was concentrated in vacuo to leave a gum. The solid and the gum were combined to give the crude hydrazide that was used with no further purification; MS m/e (M−H)− 348. A solution of 2,4,5-trifluorophenyl isothiocyanate (103 mg, 0.54 mmol) in DMA (1 mL) was added in one portion to a stirred solution of the crude hydrazide (189 mg, 0.54 mmol) in DMA (4 mL) and the reaction mixture was stirred at room temperature for 1 h. EDCI (125 mg, 0.65 mmol) was added in one portion and the reaction mixture was heated to 60° C. for 2 mins and then stirred at room temperature for 60 h. The reaction mixture was concentrated in vacuo to leave an oil. Hot water was added and the residue was stirred for 5 min to give a precipitate, which was filtered to give the title compound as a light brown solid (221 mg, 81%); 1H NMR δ 1.20 (3H, t), 1.65-1.71 (4H, m), 1.76-1.85 (4H, m), 2.52 (1H, m), 4.09 (2H, q), 4.51 (1H, s), 6.96 (2H, d), 7.67-7.74 (3H, m), 8.15-8.18 (1H, m), 10.95 (1H, s), 11.05 (1H, s); MS m/e (M−H)− 503.

Workup

  1. stirringthe reaction mixture was stirred for a further 20 mins
  2. filtrationthe mixture was filtered
  3. customto leave a solid
  4. concentrationThe filtrate was concentrated in vacuo
  5. customto leave a gum
  6. customto give the crude hydrazide that
  7. customwas used with no further purification
  8. stirringthe reaction mixture was stirred at room temperature for 1 h
  9. temperaturethe reaction mixture was heated to 60° C. for 2 mins
  10. stirringstirred at room temperature for 60 h
  11. concentrationThe reaction mixture was concentrated in vacuo
  12. customto leave an oil
  13. stirringthe residue was stirred for 5 min
  14. customto give a precipitate, which
  15. filtrationwas filtered

Sources & evidence

ORD record
ord-e39656d9115e49b396b72b5020f6aa7f
Source dataset
uspto-grants-2010_09
Patent number
US07795283B2

Reaction notes

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