Diisopropylethylamine → HCID 71492986, compound

HRID 1465876Notes

Reaction equation

HRID 1465876 reaction equation
[F:1][C:2]([F:24])([F:23])[C:3]1[CH:4]=[C:5]([C:13]2[N:17]=[CH:16][N:15](/[CH:18]=[CH:19]\[C:20]([OH:22])=O)[N:14]=2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH3:25][C:26]1[C:27]([N:32]([CH3:34])[NH2:33])=[N:28][CH:29]=[CH:30][CH:31]=1.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.CCN(C(C)C)C(C)C>CCOC(C)=O.C(Cl)Cl.CO>[F:1][C:2]([F:23])([F:24])[C:3]1[CH:4]=[C:5]([C:13]2[N:17]=[CH:16][N:15](/[CH:18]=[CH:19]\[C:20]([NH:33][N:32]([CH3:34])[C:27]3[C:26]([CH3:25])=[CH:31][CH:30]=[CH:29][N:28]=3)=[O:22])[N:14]=2)[CH:6]=[C:7]([C:9]([F:12])([F:10])[F:11])[CH:8]=1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 53403328HCID 53403328, compoundHCID 86703006(Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid

Product 1

HCID 71492986HCID 71492986, compoundYield 62.7%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-70 °C

Procedure

A 50-mL, 3-necked, round-bottomed flask was charged with a solution of (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid (0.25 g) in EtOAc (20 mL). The solution was cooled to −70° C. and was treated consecutively with 3-methyl-2-(1-methylhydrazinyl)pyridine (0.135 g, 1.0 eq.), T3P (50% in EtOAc; 1.4 mL, 4 eq.) and DIPEA (0.6 mL, 6 eq.). The clear reaction mixture was stirred at −60° C. for 4 hr. The progress of the reaction was followed by TLC analysis using 2.5% MeOH in CH2Cl2 as mobile phase and visualizing under UV. The reaction mixture was concentrated under reduced pressure (25° C., 20 mm Hg) to afford a crude compound that was purified by column chromatography (60/120 mesh SiO2 and eluting with a MeOH:CH2Cl2 gradient). The desired compound started eluting with 0.3-0.4% MeOH in dichloromethane Fractions containing the desired material were combined to obtain 0.21 g (yield: 40%) (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)-N′-methyl-N′-(3-methylpyridin-2-yl)acrylohydrazide. 1H NMR (400 MHz, DMSO-d6) δ=10.73 (s, 1H), 9.32 (s, 1H), 8.52 (s, 2H), 8.45-8.46 (d, J=4.4 Hz, 1H), 8.29 (s, 1H), 7.97-7.99 (d, J=8 Hz, 1H), 7.48-7.50 (d, J=10 Hz, 1H), 7.01-7.05 (m, 1H), 5.86-5.88 (d, J=10 Hz, 1H), 3.26 (s, 3H); LCMS for C20H14F9N6O [M+H]+ 525.35. found 525.19 (RT 3.31 min, purity 99.40%).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure (25° C., 20 mm Hg)
  2. customto afford a crude compound that
  3. customwas purified by column chromatography (60/120 mesh SiO2
  4. washeluting with a MeOH
  5. washThe desired compound started eluting with 0.3-0.4% MeOH in dichloromethane Fractions
  6. additioncontaining the desired material

Sources & evidence

ORD record
ord-75b721d91aee43dbb6305ef6f834c6c1
Source dataset
uspto-grants-2015_04
Patent number
US08999996B2

Reaction notes

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