Triethylamine → HCID 178469090, compound

HRID 572228Notes

Reaction equation

HRID 572228 reaction equation
NN.[CH2:3]([O:5][C:6](=[O:31])[C:7]1[CH:12]=[CH:11][C:10]([O:13][C@H:14]2[CH2:19][CH2:18][C@@H:17]([N:20]3[C:28](=[O:29])C4C(=CC=CC=4)C3=O)[CH2:16][CH2:15]2)=[CH:9][CH:8]=1)[CH3:4].[F:32][C:33]([F:45])([F:44])[O:34][C:35]1[CH:40]=[CH:39][C:38]([N:41]=C=O)=[CH:37][CH:36]=1.C(N(CC)CC)C>C(Cl)Cl.CN(C=O)C.O.CO>[CH2:3]([O:5][C:6](=[O:31])[C:7]1[CH:8]=[CH:9][C:10]([O:13][C@H:14]2[CH2:15][CH2:16][C@@H:17]([NH:20][C:28]([NH:41][C:38]3[CH:39]=[CH:40][C:35]([O:34][C:33]([F:32])([F:44])[F:45])=[CH:36][CH:37]=3)=[O:29])[CH2:18][CH2:19]2)=[CH:11][CH:12]=1)[CH3:4]

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 9321HydrazineHCID 92298p-(Trifluoromethoxy)phenyl isocyanateHCID 178469089HCID 178469089, compound

Product 1

HCID 178469090HCID 178469090, compoundYield 140.2%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

Anhydrous hydrazine (0.17 mL, 5.3 mmol) was added to a solution of compound 14f (1 g, 2.6 mmol) in 20 mL of CH2Cl2 followed by MeOH (20 mL) at room temperature. The reaction mixture was allowed to stir for 1 d. The resulting white precipitates were filtered off and the solvent was removed in vacuo. The resulting white solids were dissolved in aqueous 1N HCl solution and washed with CH2Cl2. The aqueous layer was basified with excess 1N NaOH solution and then extracted with CH2Cl2. After drying with MgSO4, the solvent was evaporated affording crude amine, which was used in the next step without further purification. To a solution of crude amine in DMF (50 mL) was added 4-(trifluoromethoxy)phenyl isocyanate (1.1 g, 4.3 mmol) followed by triethylamine (0.74 mL, 5.3 mmol) at 0° C. The reaction mixture was stirred overnight. The reaction mixture was poured into water, and the resulting precipitates were collected and washed with water. The crude product was purified by column chromatography to give the titled compound (1.7 g, 85%) as a white solid. 1H NMR (CDCl3): δ 7.98 (d, J=9 Hz, 2H), 7.35 (d, J=9 Hz, 2H), 7.13 (d, J=9 Hz, 2H), 6.87 (d, J=9 Hz, 2H), 6.85 (s, 1H), 5.01 (d, J=8 Hz, 1H), 4.57-4.51 (m, 1H), 4.36 (q, J=7 Hz, 2H), 3.89-3.72 (m, 1H), 2.07-1.52 (m, 8H), 1.39 (t, J=7 Hz, 3H). MS (ESI) m/z: 467.2 (M+H+).

Workup

  1. customThe resulting white precipitates
  2. filtrationwere filtered off
  3. customthe solvent was removed in vacuo
  4. dissolutionThe resulting white solids were dissolved in aqueous 1N HCl solution
  5. washwashed with CH2Cl2
  6. extractionextracted with CH2Cl2
  7. dry with materialAfter drying with MgSO4
  8. customthe solvent was evaporated
  9. customaffording crude amine, which
  10. customwas used in the next step without further purification
  11. stirringThe reaction mixture was stirred overnight
  12. customthe resulting precipitates
  13. customwere collected
  14. washwashed with water
  15. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-4f496747bf8447d4a8a3a4f5eebb8691
Source dataset
uspto-grants-2015_05
Patent number
US09029401B2

Reaction notes

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