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

HRID 1772471Notes

Reaction equation

HRID 1772471 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-amineYield 95.4%

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 (C59) (0.373 g, 0.758 mmol) in a 25 mL vial equipped with a stir bar, Vigreux column, and nitrogen was added methanol (7.58 mL) followed by hydrazine monohydrate (0.110 mL, 2.27 mmol). The reaction was heated to 50° C. until determined to be complete by LCMS. 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 resultant solid was dried in vacuo over 72 hours at 50° C. to provide 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 resultant solid was dried in vacuo over 72 hours at 50° C.

Sources & evidence

ORD record
ord-687af29ab9184d7f94a640826410882e
Source dataset
uspto-grants-2016_02
Patent number
US09249133B2

Reaction notes

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