HCID 86612970, compound → HCID 66814564, compound

HRID 1993620Notes

Reaction equation

HRID 1993620 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([C:16]2[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[C:18]([F:26])[CH:17]=2)=[N:9][C:10]2[N:14]([CH3:15])[N:13]=[N:12][N:11]=2)=[N:6][CH:7]=1.[CH2:27]([Mg]Cl)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([NH:9][C:10]2[N:14]([CH3:15])[N:13]=[N:12][N:11]=2)([C:16]2[CH:21]=[C:20]([C:22]([F:23])([F:25])[F:24])[CH:19]=[C:18]([F:26])[CH:17]=2)[CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[N:6][CH:7]=1

Participants

4

Reactant 2

HCID 86612970HCID 86612970, compoundHCID 178418336HCID 178418336, compound

Product 1

HCID 66814564HCID 66814564, compoundYield 16%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

At −78° C. to a solution of N-((5-chloropyridin-2-yl)(3-fluoro-5-(trifluoromethyl)phenyl)methylene)-1-methyl-1H-tetrazol-5-amine (135 mg, 0.35 mmol) in CH2Cl2 (2 mL) was added BnMgCl (0.4 mL, 1 M in ether, 0.4 mol) drop wise. The reaction mixture was stirred at −78° C. for 5 min, then was allowed to slowly warm up to room temperature. After 30 min, the reaction mixture was quenched by saturated NH4Cl, extracted by CH2Cl2. The organic layer was dried over MgSO4, filtered, and concentrated. The residue was purified by ISCO chromatography (12 g column) using hexanes/EtOAc (0-20%) over 16 min to give N-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)-1-methyl-1H-tetrazol-5-amine as a yellow solid (26 mg, 16% yield). LCMS RT=4.05 min [M+H] 477.26 (Phenomenex Luna C18 column, 4.6×50 mm eluting with 10-90% MeOH/H2O over 4 minutes containing 0.1% TFA; 4 mL/min, monitoring at 220 nm). NMR: 400 MHz 1H (CDCl3) 8.34 ppm, 1H, d, J=2.02 Hz; 7.63 ppm, 2H, m; 7.39 ppm, 1H, d, J=9.85 Hz; 7.25 ppm, 1H, d, J=3.79 Hz; 7.21 ppm, 1H, d, J=8.08 Hz; 7.11 ppm, 2H, m; 7.02 ppm, 2H, t, J=7.33 Hz; 6.42 ppm, 2H, d, J=7.07 Hz; 4.40 ppm, 1H, d, J=13.14 Hz; 4.09 ppm, 3H, s; 3.68 ppm, 1H, d, J=13.14 Hz.

Workup

  1. temperatureto slowly warm up to room temperature
  2. waitAfter 30 min
  3. customthe reaction mixture was quenched by saturated NH4Cl
  4. extractionextracted by CH2Cl2
  5. dry with materialThe organic layer was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by ISCO chromatography (12 g column)
  9. customover 16 min

Sources & evidence

ORD record
ord-892ac44946c04140a28e290ab3fdd939
Source dataset
uspto-grants-2010_01
Patent number
US07652023B2

Reaction notes

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