Methanol → 3-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)propan-1-amine

HRID 62038

Reaction equation

HRID 62038 reaction equation
[F:1][C:2]([F:36])([F:35])[O:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH:14]=[N:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([CH2:21][CH2:22][CH2:23][N:24]4C(=O)C5C(=CC=CC=5)C4=O)=[CH:17][CH:16]=3)=[N:11]2)=[CH:6][CH:5]=1.CO.O.NN>ClCCl>[F:36][C:2]([F:1])([F:35])[O:3][C:4]1[CH:5]=[CH:6][C:7]([N:10]2[CH:14]=[N:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([CH2:21][CH2:22][CH2:23][NH2:24])=[CH:17][CH:16]=3)=[N:11]2)=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 24654Hydrazine hydrate (1:1)HCID 904048582-(3-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)propyl)isoindoline-1,3-dione

Product 1

HCID 904042683-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)propan-1-amine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

To 2-(3-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl) propyl)isoindoline-1,3-dione (0.373 g, 0.758 mmol) in a 25 mL vial equipped with a stir bar, Vigreux column, and nitrogen was added methanol (7.6 mL) followed by hydrazine monohydrate (0.110 mL, 2.27 mmol). The reaction was heated to 50° C. The reaction mixture was cooled to room temperature and diluted with dichloromethane. The layers were separated and the aqueous layer was extracted with dichloromethane (2×). The organic layers were washed with sodium hydroxide (1 N, 4×), poured through a phase separator and concentrated. The off-white solid was dried over the weekend at 50° C. at about 25 in. Hg providing the title compound as an off-white solid (0.262 g, 95%): 1H NMR (400 MHz, DMSO-d6) δ 9.38 (s, 1H), 8.10-8.04 (m, 2H), 8.04-7.98 (m, 2H), 7.66-7.59 (m, 2H), 7.35 (d, J=8.1 Hz, 2H), 2.69-2.63 (m, 2H), 2.56 (t, J=6.9 Hz, 2H), 1.74-1.59 (m, 2H), NH2 not observed; 19F NMR (376 MHz, DMSO-d6) δ −56.96; ESIMS m/z 363 ([M+H]+).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with dichloromethane (2×)
  4. washThe organic layers were washed with sodium hydroxide (1 N, 4×)
  5. additionpoured through a phase separator
  6. concentrationconcentrated
  7. customThe off-white solid was dried over the weekend at 50° C. at about 25 in

Sources & evidence

ORD record
ord-ab0aa4f7d49247d1a0f8b85b3e97fb37
Source dataset
uspto-grants-2016_09
Patent number
US09445594B2

Linked notes

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