Diisopropylethylamine → HCID 178461206, compound

HRID 81175Notes

Reaction equation

HRID 81175 reaction equation
Br[C:2]1[N:19]([CH2:20][C@H:21]2[CH2:26][CH2:25][C@H:24]([CH3:27])[CH2:23][CH2:22]2)[C:5]2[C:6]([C:12]3[CH:13]=[N:14][CH:15]=[C:16]([Cl:18])[CH:17]=3)=[N:7][C:8]([C:10]#[N:11])=[CH:9][C:4]=2[N:3]=1.[F:28][C:29]([F:36])([F:35])[C@@H:30]1[CH2:34][CH2:33][CH2:32][NH:31]1.[F-].[K+].C(N(CC)C(C)C)(C)C>C(OCC)(=O)C.CS(C)=O>[Cl:18][C:16]1[CH:17]=[C:12]([C:6]2[C:5]3[N:19]([CH2:20][C@H:21]4[CH2:26][CH2:25][C@H:24]([CH3:27])[CH2:23][CH2:22]4)[C:2]([N:31]4[CH2:32][CH2:33][CH2:34][C@H:30]4[C:29]([F:36])([F:35])[F:28])=[N:3][C:4]=3[CH:9]=[C:8]([C:10]#[N:11])[N:7]=2)[CH:13]=[N:14][CH:15]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 522689Potassium FluorideHCID 2782840(2S)-2-(trifluoromethyl)pyrrolidineHCID 178461197HCID 178461197, compound

Product 1

HCID 178461206HCID 178461206, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a vial was added 2-bromo-4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile (Preparative Example 3.1, 350 mg, 0.79 mmol), (S)-2-(trifluoromethyl)pyrrolidine (purchased from Sigma Aldrich) (219 mg, 1.57 mmol), potassium fluoride (229 mg, 3.93 mmol), DMSO (2.4 mL), and N,N-diisopropylethylamine (0.69 mL, 3.93 mmol). The vial was sealed and heated to 100° C. for 16 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate, and washed with water and then brine. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (0-100% ethyl acetate/hexanes, linear gradient) to afford 4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-2-[(2S)-2-(trifluoromethyl)pyrrolidin-1-yl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ESI calc'd. for C25H26ClF3N6 [M+H]+ 503. found 503.

Workup

  1. customThe vial was sealed
  2. temperatureThe reaction mixture was cooled to room temperature
  3. washwashed with water
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography (0-100% ethyl acetate/hexanes, linear gradient)

Sources & evidence

ORD record
ord-5f93c462b98843c8a408d9a42ff6ff6f
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Reaction notes

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