Potassium Carbonate → HCID 73335538, compound

HRID 710629Notes

Reaction equation

HRID 710629 reaction equation
[Cl:1][C:2]1[C:3]([C:20]([F:23])([F:22])[F:21])=[N:4][N:5]([CH2:8][C:9]([N:11]2[CH2:16][CH2:15][CH2:14][C:13]3[NH:17][N:18]=[CH:19][C:12]2=3)=[O:10])[C:6]=1[CH3:7].[F:24][C:25]1[CH:26]=[CH:27][C:28](Br)=[N:29][CH:30]=1.CN[C@@H]1CCCC[C@H]1NC.C([O-])([O-])=O.[K+].[K+]>CCOC(C)=O.O1CCOCC1>[Cl:1][C:2]1[C:3]([C:20]([F:23])([F:21])[F:22])=[N:4][N:5]([CH2:8][C:9]([N:11]2[CH2:16][CH2:15][CH2:14][C:13]3[N:17]([C:28]4[CH:27]=[CH:26][C:25]([F:24])=[CH:30][N:29]=4)[N:18]=[CH:19][C:12]2=3)=[O:10])[C:6]=1[CH3:7]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 27831712-Bromo-5-fluoropyridineHCID 86711671HCID 86711671, compound

Product 1

HCID 73335538HCID 73335538, compound

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

2-(4-Chloro-5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)-1-(6,7-dihydro-1H-pyrazolo[4,3-b]pyridin-4(5H)-yl)ethanone (104 mg, 0.3 mmol) was combined with 5-fluoro-2-bromopyridine (106 mg, 0.6 mmol), 0.3 mL of dioxane, Cu(I)I (11.4 mg, 0.06 mmol, 20%), (±)-trans-N,N′-dimethylcyclohexane-1,2-diamine (21.3 mg, 0.15 mmol, 50%), and K2CO3 (83 mg, 0.6 mmol). The slurry was heated to 120° C. until complete (approx 3 hours). The reaction mixture was diluted in 4 mL of EtOAc and washed with 2×H2O. The organic layer was concentrated and the residue was purified by reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent) to provide the title compound as a white solid. 1H NMR (400 MHz, CDCl3, mixture of rotamers) δ 8.91 (s, 0.8H), 8.33 (d, J=2.7 Hz, 0.2H), 8.28 (d, J=2.9 Hz, 0.8H), 7.87-7.94 (m, 1H), 7.68-7.77 (m, 1H), 5.42 (s, 1.6H), 5.41 (s, 0.4H), 3.93 (s, 1.6H), 3.88 (s, 0.4H), 2.88 (t, J=6.4 Hz, 2H), 2.29 (s, 0.6H), 2.28 (s, 2.4H), 2.18 (m, 2H); MS: (ES) m/z calculated for C18H16ClF4N6O [M+H]+ 443.1, found 443.0.

Workup

  1. washwashed with 2×H2O
  2. concentrationThe organic layer was concentrated
  3. customthe residue was purified by reverse phase HPLC (C18 column, acetonitrile-H2O with 0.1% TFA as eluent)

Sources & evidence

ORD record
ord-c2dbb8b5f8304f97a364f5265ff62e50
Source dataset
uspto-grants-2015_11
Patent number
US09181241B2

Reaction notes

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