Triethylamine → methyl 1-(3-chloropyridin-2-yl)-3-{(E)-2-[5-(trifluoromethyl)-2H-tetrazol-2-yl]vinyl}-1H-pyrazole-5-carboxylate

HRID 1630676Notes

Reaction equation

HRID 1630676 reaction equation
[Cl:1][C:2]1[C:3]([N:8]2[C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][C:10]([CH:17](O)[CH2:18][N:19]3[N:23]=[N:22][C:21]([C:24]([F:27])([F:26])[F:25])=[N:20]3)=[N:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1.ClC1C(N2C(C(OC)=O)=CC(C(O)CN3C(C(F)(F)F)=NN=N3)=N2)=NC=CC=1.CS(Cl)(=O)=O.C(N(CC)CC)C>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:3]([N:8]2[C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][C:10](/[CH:17]=[CH:18]/[N:19]3[N:23]=[N:22][C:21]([C:24]([F:26])([F:25])[F:27])=[N:20]3)=[N:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 66587513methyl 1-(3-chloropyridin-2-yl)-3-{1-hydroxy-2-[5-(trifluoromethyl)-2H-tetrazol-2-yl]ethyl}-1H-pyrazole-5-carboxylateHCID 66587622methyl 1-(3-chloropyridin-2-yl)-3-{1-hydroxy-2-[5-(trifluoromethyl)-1H-tetrazol-1-yl]ethyl}-1H-pyrazole-5-carboxylate

Product 1

HCID 66587669methyl 1-(3-chloropyridin-2-yl)-3-{(E)-2-[5-(trifluoromethyl)-2H-tetrazol-2-yl]vinyl}-1H-pyrazole-5-carboxylateYield 61.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

225 mg (0.54 mmol) of methyl 1-(3-chloropyridin-2-yl)-3-{1-hydroxy-2-[5-(trifluoromethyl)-2H-tetrazol-2-yl]ethyl}-1H-pyrazole-5-carboxylate and methyl 1-(3-chloropyridin-2-yl)-3-{1-hydroxy-2-[5-(trifluoromethyl)-1H-tetrazol-1-yl]ethyl}-1H-pyrazole-5-carboxylate in a ratio of 66:34 were initially charged in 7.0 ml of toluene, 75.3 mg (0.65 mmol) of methanesulphonyl chloride and 166 mg (1.64 mmol) of triethylamine were added at 0° C. and the mixture was stirred at reflux temperature for 10 hours. The reaction mixture was diluted with toluene and washed with sodium bicarbonate solution. The organic phases were dried over magnesium sulphate and the solvent was distilled off under reduced pressure. The residue was chromatographed on silica gel, which gave 132 mg (45% of theory) of methyl 1-(3-chloropyridin-2-yl)-3-{(E)-2-[5-(trifluoromethyl)-2H-tetrazol-2-yl]vinyl}-1H-pyrazole-5-carboxylate and methyl 1-(3-chloropyridin-2-yl)-3-{(E)-2-[5-(trifluoromethyl)-1H-tetrazol-1-yl]vinyl}-1H-pyrazole-5-carboxylate in a ratio of 69:31. (logP: 3.37/3.49; MH+: 400.1; 1H-NMR (400 MHz, CD3CN, δ, ppm): 3.78 (s, 3H), 7.35 (m, 1H), 7.60 (m, 1H), 7.75 (m, 1H), 8.08 (m, 1H), 8.32 (m, 1H), 8.55 (m, 1H).)

Workup

  1. temperatureat reflux temperature for 10 hours
  2. washwashed with sodium bicarbonate solution
  3. dry with materialThe organic phases were dried over magnesium sulphate
  4. distillationthe solvent was distilled off under reduced pressure
  5. customThe residue was chromatographed on silica gel, which

Sources & evidence

ORD record
ord-5d2a61b8125d4cefa91e79606a9dd9c3
Source dataset
uspto-grants-2014_07
Patent number
US08791139B2

Reaction notes

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