Ethyl Acetate → HCID 71492984, compound

HRID 1465875Notes

Reaction equation

HRID 1465875 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:33]=[CH:32][CH:31]=[CH:30][N:29]=1)[NH2:27].CCOC(C)=O.CCN(C(C)C)C(C)C>C(Cl)Cl.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:33]=[CH:32][CH:31]=[CH:30][N:29]=3)=[O:22])[N:14]=2)[CH:4]=[C:3]([C:2]([F:24])([F:23])[F:1])[CH:8]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 77911Pyridine, 2-(1-methylhydrazinyl)-HCID 81531DiisopropylethylamineHCID 86703006(Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid

Product 1

HCID 71492984HCID 71492984, compoundYield 18%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A 50-mL, 3-necked, round-bottomed flask was charged with (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid (0.43 g), 2-(1-methylhydrazinyl)pyridine (0.15 g, 1.0 eq.) in EtOAc (10 mL) T3P (50% in EtOAc; 1.1 g, 1.5 eq.) and DIPEA (0.40 g, 2.5 eq.) were added under nitrogen atmosphere at −60° C. and the progress of the reaction was monitored by TLC (using 10% MeOH:CH2Cl2 as mobile phase and visualization with UV light). The reaction mixture was concentrated under reduced pressure (25° C., 20 mmHg) to afford 0.65 g of crude solid. Purification was performed on Combi-Flash Column chromatography in CH2Cl2 and MeOH (desired compound started eluting at 3.3% MeOH in CH2Cl2). The fractions containing the desired compound were combined and concentrated under reduced pressure (35° C., 20 mm Hg) to afford 90.0 mg (yield: 18%) (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)-N′-methyl-N′-(pyridin-2-yl)acrylohydrazide. 1H NMR (400 MHz, DMSO-d6) δ 9.89 (s, 1H), 9.79 (brs, 1H), 8.57-8.62 (d, 2H), 7.92-7.94 (d, J=11.2 Hz, 1H), 7.59-7.64 (m, 1H), 7.19-7.25 (q, 1H), 6.75-6.89 (m, 2H), 5.85-5.88 (d, J=10.8 Hz, 1H), 3.46 (d, 3H); LCMS for C19H15F6N6O [M+H]+ 457.35. found 456.26 (RT 2.52 min, purity: 100.0%).

Workup

  1. additionwere added under nitrogen atmosphere at −60° C.
  2. concentrationThe reaction mixture was concentrated under reduced pressure (25° C., 20 mmHg)
  3. customto afford 0.65 g of crude solid
  4. customPurification
  5. additionThe fractions containing the desired compound
  6. concentrationconcentrated under reduced pressure (35° C., 20 mm Hg)

Sources & evidence

ORD record
ord-ead91824c4e843bbb9f0d56b6a30830c
Source dataset
uspto-grants-2015_04
Patent number
US08999996B2

Reaction notes

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