Hydrochloric Acid → HCID 178520528, compound

HRID 1486975Notes

Reaction equation

HRID 1486975 reaction equation
[F:1][C:2]([F:24])([F:23])[C:3]1[CH:4]=[C:5]([C:13]2[NH:14][C:15](/[CH:18]=[CH:19]\[C:20]([OH:22])=O)=[N:16][N:17]=2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.Cl.[F:26][C:27]1([F:31])[CH2:30][NH:29][CH2:28]1.Cl.CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1>ClCCl.CO.ClCCl.C(Cl)CCl>[F:11][C:9]([F:10])([F:12])[C:7]1[CH:6]=[C:5]([C:13]2[NH:14][C:15](/[CH:18]=[CH:19]\[C:20]([N:29]3[CH2:30][C:27]([F:31])([F:26])[CH2:28]3)=[O:22])=[N:16][N:17]=2)[CH:4]=[C:3]([C:2]([F:24])([F:23])[F:1])[CH:8]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27582473,3-Difluoroazetidine hydrochlorideHCID 178525371HCID 178525371, compound

Product 1

HCID 178520528HCID 178520528, compoundYield 78%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

In a 3-neck 50 mL round-bottomed flask, (Z)-3-(5-(3,5-bis(trifluoromethyl)phenyl)-4H-1,2,4-triazol-3-yl)acrylic acid (2) (0.065 g, 1 eq.), 3,3-difluoroazetidine HCl (0.028 g, 1.2 eq.) and EDC. HCl (0.042 g, 1.2 eq.) was dissolved in dichloromethane (5 mL). DIPEA (0.028 g, 1.2 eq.) was added at −5° C. followed by HOBt (0.033 g, 1.2 eq.) added at same temperature. Reaction was maintained at this temp for 1 h. Reaction completion was monitored on TLC using MeOH: dichloromethane (0.5:9.5) as mobile phase. The reaction mixture was quenched into the ice-water slurry (50 mL) and was extracted with ethyl acetate (3×20 mL). Organic layer was washed with brine solution (3×25 mL). The organic layer was dried using anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to provide the 0.80 g crude compound which was purified by column chromatography using ethylacetate and hexane as mobile phase. Product was eluted in 35% ethylacetate in hexane to afford 0.055 g (78%) title compound.

Workup

  1. additionadded at same temperature
  2. customReaction
  3. temperaturewas maintained at this temp for 1 h
  4. customReaction completion
  5. customThe reaction mixture was quenched into the ice-water slurry (50 mL)
  6. extractionwas extracted with ethyl acetate (3×20 mL)
  7. washOrganic layer was washed with brine solution (3×25 mL)
  8. customThe organic layer was dried
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customto provide the 0.80 g crude compound which
  12. customwas purified by column chromatography
  13. washProduct was eluted in 35% ethylacetate in hexane

Sources & evidence

ORD record
ord-39d10fde058d418ebc02eba34ae54b1b
Source dataset
uspto-grants-2016_08
Patent number
US09428490B2

Reaction notes

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