Triethylamine → Benzyl 3-(5-cyano-4-(2,6-difluorophenyl)-N-isopropyl-1H-1,2,3-triazole-1-carboxamido)benzoate

HRID 2097674Notes

Reaction equation

HRID 2097674 reaction equation
[CH:1]([NH:4][C:5]1[CH:6]=[C:7]([CH:18]=[CH:19][CH:20]=1)[C:8]([O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:9])([CH3:3])[CH3:2].C(N(CC)CC)C.ClC(Cl)(O[C:32](=[O:38])OC(Cl)(Cl)Cl)Cl.[F:40][C:41]1[CH:46]=[CH:45][CH:44]=[C:43]([F:47])[C:42]=1[C:48]1[N:49]=[N:50][NH:51][C:52]=1[C:53]#[N:54]>ClCCl.CN(C1C=CN=CC=1)C.CCOC(C)=O>[C:53]([C:52]1[N:51]([C:32]([N:4]([C:5]2[CH:6]=[C:7]([CH:18]=[CH:19][CH:20]=2)[C:8]([O:10][CH2:11][C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)=[O:9])[CH:1]([CH3:3])[CH3:2])=[O:38])[N:50]=[N:49][C:48]=1[C:42]1[C:43]([F:47])=[CH:44][CH:45]=[CH:46][C:41]=1[F:40])#[N:54]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 58501909Benzyl 3-(isopropylamino)benzoateHCID 1785106704-(2,6-difluorophenyl)-1H-1,2,3-triazole-5-carbonitrile

Product 1

HCID 58501889Benzyl 3-(5-cyano-4-(2,6-difluorophenyl)-N-isopropyl-1H-1,2,3-triazole-1-carboxamido)benzoate

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of benzyl 3-(isopropylamino)benzoate (5) in dry dichloromethane (0.4 M) under Ar at 0° C. was added triethylamine (1.5 equiv) followed by triphosgene (1.5 equiv). The resulting mixture was stirred at rt for 15 min and was concentrated in vacuo. The residue was suspended in dry toluene (0.4 M), DMAP (1.0 equiv) and 4-(2,6-difluorophenyl)-1H-1,2,3-triazole-5-carbonitrile (2) (1.0 equiv) were added and the resulting suspension was heated to reflux for 1 h, then cooled to rt, diluted with AcOEt and washed with water, 10% HCl and brine. The organic layer was dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by flash chromatography (Hexanes/AcOEt as eluant). Benzyl 3-(5-cyano-4-(2,6-difluorophenyl)-N-isopropyl-1H-1,2,3-triazole-1-carboxamido)benzoate (6) was obtained as a pale yellow foam.

Workup

  1. concentrationwas concentrated in vacuo
  2. temperaturethe resulting suspension was heated
  3. temperatureto reflux for 1 h
  4. temperaturecooled to rt
  5. washwashed with water, 10% HCl and brine
  6. dry with materialThe organic layer was dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by flash chromatography (Hexanes/AcOEt as eluant)

Sources & evidence

ORD record
ord-76b01bf5e1bb4d20b77aa21e9aeb2d7a
Source dataset
uspto-grants-2013_05
Patent number
US08450350B2

Reaction notes

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