Diisopropylethylamine → HCID 178461219, compound

HRID 81099Notes

Reaction equation

HRID 81099 reaction equation
Br[C:2]1[N:12]([CH2:13][C@H:14]2[CH2:19][CH2:18][C@H:17]([CH3:20])[CH2:16][CH2:15]2)[C:5]2[C:6]([Cl:11])=[N:7][C:8]([Cl:10])=[CH:9][C:4]=2[N:3]=1.[C:21]1([C@@H:27]2[CH2:32][O:31][CH2:30][CH2:29][NH:28]2)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[F-].[K+].C(N(CC)C(C)C)(C)C>C(OCC)(=O)C.CS(C)=O>[Cl:11][C:6]1[C:5]2[N:12]([CH2:13][C@H:14]3[CH2:19][CH2:18][C@H:17]([CH3:20])[CH2:16][CH2:15]3)[C:2]([N:28]3[CH2:29][CH2:30][O:31][CH2:32][C@H:27]3[C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[N:3][C:4]=2[CH:9]=[C:8]([Cl:10])[N:7]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 522689Potassium FluorideHCID 13110207(R)-3-phenylmorpholineHCID 178461196HCID 178461196, compound

Product 1

HCID 178461219HCID 178461219, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a vial were added 2-bromo-4,6-dichloro-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine (3.13 g, 8.30 mmol), (R)-3-phenylmorpholine (purchased from Beyond Pharmatech) (2.71 g, 16.6 mmol), potassium fluoride (2.41 g, 41.5 mmol), DMSO (25.5 mL), and N,N-diisopropylethylamine (7.25 mL, 41.5 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 (0-60% ethyl acetate/hexanes, linear gradient) to afford 4,6-dichloro-3-[(trans-4-methylcyclohexyl)methyl]-2-[(3R)-3-phenylmorpholin-4-yl]-3H-imidazo[4,5-c]pyridine. MS ESI calc'd. for C24H28Cl2N4O [M+H]+ 459. found 459.

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 (0-60% ethyl acetate/hexanes, linear gradient)

Sources & evidence

ORD record
ord-d68058e6991d4cc689fbb6d2456bf0be
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Reaction notes

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