Diisopropylethylamine → HCID 71492988, compound

HRID 1465878Notes

Reaction equation

HRID 1465878 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][N:26]([C:28]1[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=1)[NH2:27].C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.CCN(C(C)C)C(C)C>C(Cl)Cl.O.CO>[F:11][C:9]([F:12])([F:10])[C:7]1[CH:6]=[C:5]([C:13]2[N:17]=[CH:16][N:15](/[CH:18]=[CH:19]\[C:20]([NH:27][N:26]([CH3:25])[C:28]3[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=3)=[O:22])[N:14]=2)[CH:4]=[C:3]([C:2]([F:24])([F:23])[F:1])[CH:8]=1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 22591580HCID 22591580, compoundHCID 86703006(Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid

Product 1

HCID 71492988HCID 71492988, compoundYield 43%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-60 °C

Procedure

A 50-mL, 3-necked, round bottom flask charged with a solution of (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid (0.25) in CH2Cl2 (12 mL) was treated with 3-(1-methylhydrazinyl)pyridine (0.105 g, 1.2 eq.). The mixture was cooled to −60° C. and treated with T3P (propyl phosphonic anhydride; 0.50 mL, 1.2 eq.) and DIPEA (0.24 mL, 2.0 eq.) and stirred for 1 h. The progress of the reaction was followed by TLC analysis using 10% MeOH:CH2Cl2 as mobile phase and visualizing under UV light. The reaction mixture was then poured into water (50 mL) and extracted with CH2Cl2 (2×50 mL). The combined organic layers were washed with brine (50 mL), dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure (25° C., 20 mmHg) to afford crude compound which was purified by column chromatography (SiO2, 60/120 mesh, MeOH:CH2Cl2 as mobile phase). The desired compound started eluting in 3.0% MeOH:CH2Cl2. The fractions containing the compound were collected and concentrated under reduced pressure to afford 140 mg (yield: 43%) (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)-N′-methyl-N′-(pyridin-3-yl)acrylohydrazide. 1H NMR (400 MHz, DMSO-d6) δ, 10.55 (s, 1H), 9.41 (s, 1H), 9.15 (s, 2H), 8.58 (s, 1H), 8.53 (s, 1H), 8.29 (s, 1H), 7.51-7.54 (d, J=10.4 Hz, 1H), 7.18-7.22 (m, 2H), 6.05-6.07 (d, J=10.4 Hz, 1H), 3.20 (s, 3H); LCMS for C19H15F6N6O [M+H]+ 457.35. found 457.19 (RT 2.43 min, purity: 83.48%).

Workup

  1. extractionextracted with CH2Cl2 (2×50 mL)
  2. washThe combined organic layers were washed with brine (50 mL)
  3. dry with materialdried over anhydrous MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure (25° C., 20 mmHg)
  6. customto afford crude compound which
  7. customwas purified by column chromatography (SiO2, 60/120 mesh, MeOH:CH2Cl2 as mobile phase)
  8. washThe desired compound started eluting in 3.0% MeOH
  9. additionThe fractions containing the compound
  10. customwere collected
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-6511f316c846452e9906cdb6225e8653
Source dataset
uspto-grants-2015_04
Patent number
US08999996B2

Reaction notes

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