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

HRID 1772545Notes

Reaction equation

HRID 1772545 reaction equation
[F:1][C:2]([F:26])([F:25])[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][C:22](=O)[CH3:23])=[CH:17][CH:16]=3)=[N:11]2)=[CH:6][CH:5]=1.C([O-])(=O)C.[NH4+].C([BH3-])#[N:33].[Na+]>CO>[F:1][C:2]([F:26])([F:25])[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][CH:22]([NH2:33])[CH3:23])=[CH:17][CH:16]=3)=[N:11]2)=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 517165Ammonium AcetateHCID 5003444Sodium cyanoborohydrideHCID 904125151-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)propan-2-one

Product 1

HCID 904118321-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)propan-2-amineYield 102.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

1-(4-(1-(4-(Trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)propan-2-one (CB57) (1.0 g, 2.8 mmol) and ammonium acetate (1.7 g, 22 mmol) were combined in dry methanol (22 mL) and stirred at room temperature while sodium cyanoborohydride (0.17 g, 2.7 mmol) was added in 3 equal portions over 30 minutes. The reaction was stirred overnight. The reaction was concentrated and partitioned between aqueous potassium carbonate and diethyl ether. The layers were separated, dried, filtered, and concentrated. Purification by reverse-phase flash column (C18) chromatography using 0-100% acetonitrile/water as eluent provided the title compound as a tan solid (1.0 g, 38%): mp 140-160° C.; 1H NMR (400 MHz, CDOD3) d 9.13 (s, 1H), 8.09 (d, J=8.0 Hz, 2H), 8.00 (d, J=9.0 Hz, 2H), 7.52 7.43 (m, 2H), 7.35 (d, J=8.0 Hz, 2H), 3.40-3.33 (m, 1H), 2.86 (t, J=6.7 Hz, 1H), 2.77 (dd, J=13.3, 7.3 Hz, 1H), 1.18 (d, J=6.2 Hz, 3H) (NH2 not observed); ESIMS m/z 363 ([M+H]+).

Workup

  1. additionwas added in 3 equal portions over 30 minutes
  2. concentrationThe reaction was concentrated
  3. custompartitioned between aqueous potassium carbonate and diethyl ether
  4. customThe layers were separated
  5. customdried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by reverse-phase flash column (C18) chromatography

Sources & evidence

ORD record
ord-2dedcaa2fa574464a1b76e868ab8bef5
Source dataset
uspto-grants-2016_02
Patent number
US09249133B2

Reaction notes

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