Diisopropylethylamine → HCID 178461210, compound

HRID 1852777Notes

Reaction equation

HRID 1852777 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.Cl.[F:29][CH2:30][C@@H:31]1[CH2:35][CH2:34][CH2:33][NH:32]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:32]4[CH2:33][CH2:34][CH2:35][C@H:31]4[CH2:30][F:29])=[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 53346549(2S)-2-(fluoromethyl)pyrrolidine hydrochlorideHCID 178461197HCID 178461197, compound

Product 1

HCID 178461210HCID 178461210, 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, 382.2 mg, 0.86 mmol), (S)-2-(fluoromethyl)pyrrolidine hydrochloride (240 mg, 1.72 mmol), potassium fluoride (250 mg, 4.30 mmol), DMSO (2.6 mL), and N,N-diisopropylethylamine (0.75 mL, 4.30 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)-2-[(2S)-2-(fluoromethyl)pyrrolidin-1-yl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ESI calc'd. for C25H28ClFN6 [M+H]+ 467. found 467.

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-fddae614bae74818b1c5eb8fe62a3749
Source dataset
uspto-grants-2015_02
Patent number
US08962611B2

Reaction notes

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