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

HRID 710671Notes

Reaction equation

HRID 710671 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH3:12])[C:9]([OH:11])=O)=[CH:4][C:3]=1[C:13]([F:16])([F:15])[F:14].[F:17][C:18]1[CH:23]=[CH:22][C:21]([N:24]2[C:32]3[CH2:31][CH2:30][CH2:29][NH:28][C:27]=3[CH:26]=[N:25]2)=[CH:20][CH:19]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH3:12])[C:9]([N:28]2[CH2:29][CH2:30][CH2:31][C:32]3[N:24]([C:21]4[CH:22]=[CH:23][C:18]([F:17])=[CH:19][CH:20]=4)[N:25]=[CH:26][C:27]2=3)=[O:11])=[CH:4][C:3]=1[C:13]([F:16])([F:15])[F:14]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 572006802-[4-Chloro-3-(trifluoromethyl)phenyl]propanoic acidHCID 679846101-(4-fluorophenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-b]pyridine

Product 1

HCID 733361142-[4-chloro-3-(trifluoromethyl)phenyl]-1-[1-(4-fluorophenyl)-6,7-dihydro-5H-pyrazolo[4,3-b]pyridin-4-yl]propan-1-oneYield 29%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 2-[4-chloro-3-(trifluoromethyl)phenyl]propanoic acid (47 mg, 0.184 mmol) and 1-(4-fluorophenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-b]pyridine (40 mg, 0.184 mmol) in DMF (1 mL) was added Hunig's base (59 mg, 0.46 mmol) and 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uranium hexafluorophosphate methanaminium (HATU) (77 mg, 0.2 mmol). The mixture was stirred at room temperature for 1 hour, and then was partitioned between water (4 mL) and ethyl acetate (6 mL). The organic layer was washed with brine and 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 (24 mg, 29%). 1H NMR (400 MHz, CDCl3) δ 8.51 (s, 1H), 7.62 (d, J=2.0 Hz, 1H), 7.48-7.42 (m, 4H), 7.16-7.11 (m, 2H), 4.11 (m, 1H), 3.76 (m, 1H), 3.52 (m, 1H), 2.77 (m, 2H), 1.96 (m, 1H), 1.80 (m, 1H), 1.55 (d, J=7.2 Hz, 3H); MS: (ES) m/z calculated for C22H18ClF4N3O [M+H]+ 452.1, found 452.1.

Workup

  1. customwas partitioned 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-73a62c2dabeb480eb99d3de04c2c37a5
Source dataset
uspto-grants-2015_11
Patent number
US09181241B2

Reaction notes

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