bis(1-methyl-1H-1,2,3-triazol-5-yl)methanone → HCID 86716150, compound

HRID 627570Notes

Reaction equation

HRID 627570 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]([F:15])([F:14])[F:13])[C:6]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[C:5]2[C:22]([F:25])([F:24])[F:23].C([Mg]Cl)(C)C.[CH3:31][N:32]1[C:36]([C:37]([C:39]2[N:43]([CH3:44])[N:42]=[N:41][CH:40]=2)=[O:38])=[CH:35][N:34]=[N:33]1>C1COCC1>[CH3:44][N:43]1[C:39]([C:37]([C:36]2[N:32]([CH3:31])[N:33]=[N:34][CH:35]=2)([C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[N:8]=[C:7]([C:12]([F:15])([F:13])[F:14])[C:6]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:5]3[C:22]([F:25])([F:24])[F:23])[OH:38])=[CH:40][N:41]=[N:42]1

Participants

5

Reactant 3

HCID 86715669bis(1-methyl-1H-1,2,3-triazol-5-yl)methanone2×HCID 867160666-Bromo-3-phenyl-2,4-bis(trifluoromethyl)quinoline2×HCID 178418918HCID 178418918, compound

Product 1

HCID 86716150HCID 86716150, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A ˜−70° C. solution of 6-iodo-3-phenyl-2,4-bis(trifluoromethyl)quinoline (152 mg, 0.326 mmol; Intermediate 8, step d) in THF (0.322 mL) was treated with iPrMgCl (2.06 M in THF; 0.158 mL, 0.326 mmol) dropwise via syringe under argon over the course of 30 sec to provide an amber solution that became a yellow opaque slurry within 2 min. After 2 additional min the dark yellow opaque slurry was removed from the cold bath and immediately treated rapidly dropwise with a pre-formed solution of bis(1-methyl-1H-1,2,3-triazol-5-yl)methanone (74.2 mg, 0.386 mmol; Intermediate 57) in THF (2.6 mL) over 45 sec. The reaction was stirred at room temperature for 3 hours and was then quenched with 5 M NH4Cl (1 mL). The aqueous layer was extracted with MTBE (1×3 mL), and the combined organic layers were dried (Na2SO4), filtered, and concentrated. The residue was dry load flash chromatographed with a heptane to 80% EtOAc/heptane gradient to provide the title compound as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 8.45 (d, J=8.59 Hz, 1H), 8.29 (br. s., 1H), 8.21 (s, 1H), 7.87 (d, J=9.09 Hz, 1H), 7.40-7.56 (m, 5H), 7.29 (s, 2H), 3.87 (s, 6H). MS m/e 534.2 [M+H]+.

Workup

  1. customto provide an amber solution that
  2. customwithin 2 min
  3. customAfter 2 additional min the dark yellow opaque slurry was removed from the cold bath
  4. customwas then quenched with 5 M NH4Cl (1 mL)
  5. extractionThe aqueous layer was extracted with MTBE (1×3 mL)
  6. dry with materialthe combined organic layers were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was dry load flash
  10. customchromatographed with a heptane to 80% EtOAc/heptane gradient

Sources & evidence

ORD record
ord-7d818b49d13d448aa61a177fff67c5b1
Source dataset
uspto-grants-2016_04
Patent number
US09309222B2

Reaction notes

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