Cesium fluoride → HCID 178467427, compound

HRID 81287Notes

Reaction equation

HRID 81287 reaction equation
Br[C:2]1[N:18]([CH2:19][C@H:20]2[CH2:25][CH2:24][C@H:23]([CH3:26])[CH2:22][CH2:21]2)[C:5]2[C:6]([O:11][CH:12]([CH:14]3[CH2:17][CH2:16][CH2:15]3)[CH3:13])=[N:7][C:8]([Cl:10])=[CH:9][C:4]=2[N:3]=1.[C:27]1([C@@H:33]2[CH2:38][O:37][CH2:36][CH2:35][NH:34]2)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.[F-].[Cs+]>CS(C)=O.O>[Cl:10][C:8]1[N:7]=[C:6]([O:11][CH:12]([CH:14]2[CH2:17][CH2:16][CH2:15]2)[CH3:13])[C:5]2[N:18]([CH2:19][C@H:20]3[CH2:25][CH2:24][C@H:23]([CH3:26])[CH2:22][CH2:21]3)[C:2]([N:34]3[CH2:35][CH2:36][O:37][CH2:38][C@H:33]3[C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[N:3][C:4]=2[CH:9]=1

Participants

6

Reactant 3

HCID 25953Cesium fluorideHCID 13110207(R)-3-phenylmorpholineHCID 178467426HCID 178467426, compound

Product 1

HCID 178467427HCID 178467427, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
125 °C

Procedure

To a solution of 2-bromo-6-chloro-4-(1-cyclobutylethoxy)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridine (1.5 g, 3.40 mmol) in DMSO (15 mL), in a microwave tube was added (R)-3-phenylmorpholine (797 mg, 4.77 mmol) and cesium fluoride (3.6 g, 23.8 mmol). The reaction was heated at 125° C. in a microwave for 45 mins. The reaction was then diluted with water (50 mL) and extracted with ethyl acetate (2×30 mL). The combined organic extracts were washed with water (20 mL) and brine (20 mL), dried over anhydrous Na2SO4, filtered, and concentrated. The residue was purified by silica gel chromatography (eluting with 8-10% EtOAc/petroleum ether) to yield (3R)-4-(6-chloro-4-(1-cyclobutylethoxy)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridin-2-yl)-3-phenylmorpholine. MS ES/APCl calc'd. for C30H39ClN4O2 [M+H]+ 523. found 523.

Workup

  1. extractionextracted with ethyl acetate (2×30 mL)
  2. washThe combined organic extracts were washed with water (20 mL) and brine (20 mL)
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography (eluting with 8-10% EtOAc/petroleum ether)

Sources & evidence

ORD record
ord-1dd85ac7cfec4e119d813792de5bd221
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Reaction notes

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