4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzaldehyde → 1-(2-fluoro-6-propan-2-ylphenyl)-3-[(E)-[4-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]phenyl]methylideneamino]thiourea

HRID 1475612Notes

Reaction equation

HRID 1475612 reaction equation
[F:1][C:2]([F:24])([F:23])[O:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH:14]=[N:13][C:12]([C:15]3[CH:22]=[CH:21][C:18]([CH:19]=O)=[CH:17][CH:16]=3)=[N:11]2)=[CH:6][CH:5]=1.[F:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([CH:32]([CH3:34])[CH3:33])[C:27]=1[NH:35][C:36]([NH:38][NH2:39])=[S:37]>CO>[F:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([CH:32]([CH3:33])[CH3:34])[C:27]=1[NH:35][C:36]([NH:38]/[N:39]=[CH:19]/[C:18]1[CH:21]=[CH:22][C:15]([C:12]2[N:13]=[CH:14][N:10]([C:7]3[CH:8]=[CH:9][C:4]([O:3][C:2]([F:24])([F:23])[F:1])=[CH:5][CH:6]=3)[N:11]=2)=[CH:16][CH:17]=1)=[S:37]

Participants

4

Reactant 2

HCID 578244624-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzaldehydeHCID 86691469N-(2-fluoro-6-isopropylphenyl)hydrazinecarbothioamide

Product 1

HCID 897237331-(2-fluoro-6-propan-2-ylphenyl)-3-[(E)-[4-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]phenyl]methylideneamino]thioureaYield 73.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of 4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzaldehyde (0.760 g, 2.28 mmol) in methanol (22.8 mL) in a 100 mL round-bottomed flask equipped with a magnetic stir bar and reflux condenser was added N-(2-fluoro-6-isopropylphenyl)hydrazinecarbothioamide (0.518 g, 2.28 mmol), and the reaction was heated to 65° C. and stirred for 6 hours. The temperature was lowered to 50° C. and the reaction was stirred overnight. The reaction was cooled to room temperature and the resulting solid was filtered, washed with methanol, and dried under vacuum (25 in Hg) at 55° C. to give the title compound (0.907 g, 1.67 mmol, 73% yield) as a white solid: mp 210-212° C.; 1H NMR (400 MHz, CDCl3) δ 9.54 (s, 1H), 8.60 (s, 1H), 8.56 (s, 1H), 8.30-8.22 (m, 2H), 7.92 (s, 1H), 7.86-7.76 (m, 4H), 7.44-7.38 (m, 2H), 7.35 (dd, J=8.1, 5.6 Hz, 1H), 7.18 (d, J=7.9 Hz, 1H), 7.04 (ddd, J=9.4, 8.2, 1.3 Hz, 1H), 3.22 (p, J=6.9 Hz, 1H), 1.29 (d, J=6.9 Hz, 6H); ESIMS m/z 544 ([M+H]+).

Workup

  1. temperaturereflux condenser
  2. customwas lowered to 50° C.
  3. stirringthe reaction was stirred overnight
  4. temperatureThe reaction was cooled to room temperature
  5. filtrationthe resulting solid was filtered
  6. washwashed with methanol
  7. customdried under vacuum (25 in Hg) at 55° C.

Sources & evidence

ORD record
ord-b4dc4878c74d4c7e80babfb93db2ac96
Source dataset
uspto-grants-2015_04
Patent number
US09018388B2

Reaction notes

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