Diisopropylethylamine → 1-[1-(4-fluorophenyl)-6,7-dihydro-5H-pyrazolo[4,3-b]pyridin-4-yl]-2-[5-methyl-3-(trifluoromethyl)-1,2,4-triazol-1-yl]propan-1-one

HRID 710679Notes

Reaction equation

HRID 710679 reaction equation
[CH3:1][C:2]1[N:6]([CH:7]([CH3:11])[C:8]([OH:10])=O)[N:5]=[C:4]([C:12]([F:15])([F:14])[F:13])[N:3]=1.[F:16][C:17]1[CH:22]=[CH:21][C:20]([N:23]2[C:31]3[CH2:30][CH2:29][CH2:28][NH:27][C:26]=3[CH:25]=[N:24]2)=[CH:19][CH:18]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[F:16][C:17]1[CH:18]=[CH:19][C:20]([N:23]2[C:31]3[CH2:30][CH2:29][CH2:28][N:27]([C:8](=[O:10])[CH:7]([N:6]4[C:2]([CH3:1])=[N:3][C:4]([C:12]([F:15])([F:14])[F:13])=[N:5]4)[CH3:11])[C:26]=3[CH:25]=[N:24]2)=[CH:21][CH:22]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 679846101-(4-fluorophenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-b]pyridineHCID 867116872-[5-Methyl-3-(trifluoromethyl)-1,2,4-triazol-1-yl]propanoic acid

Product 1

HCID 733362121-[1-(4-fluorophenyl)-6,7-dihydro-5H-pyrazolo[4,3-b]pyridin-4-yl]-2-[5-methyl-3-(trifluoromethyl)-1,2,4-triazol-1-yl]propan-1-oneYield 30%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 2-[5-methyl-3-(trifluoromethyl)-1,2,4-triazol-1-yl]propanoic acid (0.051 g, 0.23 mmol) and 1-(4-fluorophenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-b]pyridine (0.050 g, 0.23 mmol) in DMF (1 mL) were added Hunig's base (0.059 g, 0.46 mmol) and 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uranium hexafluorophosphate methanaminium (HATU) (0.096 g, 0.25 mmol). The mixture was stirred at room temperature for 1 hour and then partitioned between water (4 mL) and ethyl acetate (6 mL). The organic layer was washed with brine, dried (Na2SO4), filtered, concentrated in vacuo, and purified by reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent) to give the desired product as a white solid (0.029 g, 0.069 mmol, 30%). 1H NMR (400 MHz, CDCl3) δ 8.42 (s, 1H), 7.44 (ddd, J=10.4, 5.2, 2.8 Hz, 2H), 7.21-7.10 (m, 2H), 5.61 (q, J=7.1 Hz, 1H); 3.77 (ddd, J=12.6, 7.5, 3.0 Hz, 1H), 3.52 (ddd, J=12.5, 8.4, 3.0 Hz, 1H), 2.82 (td, J=6.4, 2.4 Hz, 2H), 2.52 (s, 3H), 2.10-1.80 (m, 5H); MS: (ES) m/z calculated for C19H18ClF3N6O [M+H]+ 423.1, found 422.9.

Workup

  1. custompartitioned between water (4 mL) and ethyl acetate (6 mL)
  2. washThe organic layer was washed with brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. custompurified by reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent)

Sources & evidence

ORD record
ord-052bd1e7acbd47fba9dbe7eb0a8b2820
Source dataset
uspto-grants-2015_11
Patent number
US09181241B2

Reaction notes

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