Sodium hydride → (4,4-Difluoro-piperidin-1-yl)-[5-(1-isopropyl-piperidin-4-yloxy)-1-methanesulfonyl-1H-pyrrolo[2,3-b]pyridin-2-yl]-methanone

HRID 1437713Notes

Reaction equation

HRID 1437713 reaction equation
[F:1][C:2]1([F:29])[CH2:7][CH2:6][N:5]([C:8]([C:10]2[NH:28][C:13]3=[N:14][CH:15]=[C:16]([O:18][CH:19]4[CH2:24][CH2:23][N:22]([CH:25]([CH3:27])[CH3:26])[CH2:21][CH2:20]4)[CH:17]=[C:12]3[CH:11]=2)=[O:9])[CH2:4][CH2:3]1.[H-].[Na+].[CH3:32][S:33](Cl)(=[O:35])=[O:34]>CN(C=O)C>[F:29][C:2]1([F:1])[CH2:7][CH2:6][N:5]([C:8]([C:10]2[N:28]([S:33]([CH3:32])(=[O:35])=[O:34])[C:13]3=[N:14][CH:15]=[C:16]([O:18][CH:19]4[CH2:20][CH2:21][N:22]([CH:25]([CH3:27])[CH3:26])[CH2:23][CH2:24]4)[CH:17]=[C:12]3[CH:11]=2)=[O:9])[CH2:4][CH2:3]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 31297Methanesulfonyl chlorideHCID 16727356(4,4-Difluoro-piperidin-1-yl)-[5-(1-isopropyl-piperidin-4-yloxy)-1H-pyrrolo[2,3-b]pyridin-2-yl]-methanone

Product 1

HCID 16727132(4,4-Difluoro-piperidin-1-yl)-[5-(1-isopropyl-piperidin-4-yloxy)-1-methanesulfonyl-1H-pyrrolo[2,3-b]pyridin-2-yl]-methanoneYield 44%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

The suspension of 0.25 g (0.6 mmol) (4,4-difluoro-piperidin-1-yl)-[5-(1-isopropyl-piperidin-4-yloxy)-1H-pyrrolo[2,3-b]pyridin-2-yl]-methanone (example 13) and 30 mg (0.68 mmol; 55% dispersion in mineral oil) sodium hydride in 3 ml DMF was heated to 70° C. To the resulting solution 53 μl (77 mg, 0.67 mmol) methanesulfonyl chloride were added. After 1.5 h the heating bath was removed and the solution was poured on water and was extracted three times with ethyl acetate. The combined organic layers were washed with water and brine, dried over magnesium sulfate, filtered and evaporated. The crude product was purified by flash-chromatography on silica gel with dichloromethane:methanol:ammonia (9:1:0.1 v/v) to give 13 mg (44%) of the product as a light brown foam.

Workup

  1. customAfter 1.5 h the heating bath was removed
  2. additionthe solution was poured on water
  3. extractionwas extracted three times with ethyl acetate
  4. washThe combined organic layers were washed with water and brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude product was purified by flash-chromatography on silica gel with dichloromethane:methanol:ammonia (9:1:0.1 v/v)

Sources & evidence

ORD record
ord-fe51c294db1a4bf18daf6615db4a3499
Source dataset
uspto-grants-2009_11
Patent number
US07622466B2

Reaction notes

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