9-Benzenesulfonyl-3-bromo-5-[1-(2,2-difluoroethyl)-piperidin-4-yloxy]-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile → 9-Benzenesulfonyl-5-[1-(2,2-difluoroethyl)-piperidin-4-yloxy]-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

HRID 60324Notes

Reaction equation

HRID 60324 reaction equation
[C:1]1([S:7]([N:10]2[C:14]3[CH:15]=[N:16][C:17]([C:30]#[N:31])=[C:18]([O:19][CH:20]4[CH2:25][CH2:24][N:23]([CH2:26][CH:27]([F:29])[F:28])[CH2:22][CH2:21]4)[C:13]=3[C:12]3[CH:32]=[C:33](Br)[CH:34]=[N:35][C:11]2=3)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>[Pd].ClCCl>[C:1]1([S:7]([N:10]2[C:14]3[CH:15]=[N:16][C:17]([C:30]#[N:31])=[C:18]([O:19][CH:20]4[CH2:21][CH2:22][N:23]([CH2:26][CH:27]([F:28])[F:29])[CH2:24][CH2:25]4)[C:13]=3[C:12]3[CH:32]=[CH:33][CH:34]=[N:35][C:11]2=3)(=[O:9])=[O:8])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

4

Reactant 1

HCID 583652179-Benzenesulfonyl-3-bromo-5-[1-(2,2-difluoroethyl)-piperidin-4-yloxy]-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

Product 1

HCID 583651179-Benzenesulfonyl-5-[1-(2,2-difluoroethyl)-piperidin-4-yloxy]-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrileYield 32%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 6344DichloromethaneSolvent

Procedure

A suspension of 9-benzenesulfonyl-3-bromo-5-[1-(2,2-difluoroethyl)-piperidin-4-yloxy]-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (240 mg, 0.42 mmol) and palladium on carbon (10 wt %, 50 mg) in industrial methylated spirits (5 mL) and dichloromethane (5 mL) was stirred at ambient temperature under an atmosphere of hydrogen for 5 days. The reaction vessel was purged with nitrogen then the reaction mixture was filtered through a PTFE filter cup. The filtrate was evaporated in-vacuo and the resultant residue purified by flash chromatography (silica, 10 g column, ISCO, 0-2% methanol in dichloromethane) to afford the title compound as an off-white solid (66 mg, 32%). LCMS (Method B): RT=3.74 min, M+H+=518.

Workup

  1. customThe reaction vessel was purged with nitrogen
  2. filtrationthe reaction mixture was filtered through a PTFE
  3. filtrationfilter cup
  4. customThe filtrate was evaporated in-vacuo
  5. customthe resultant residue purified by flash chromatography (silica, 10 g column, ISCO, 0-2% methanol in dichloromethane)

Sources & evidence

ORD record
ord-9de385b8aab34c2cac41e520ae0acc6b
Source dataset
uspto-grants-2016_09
Patent number
US09440976B2

Reaction notes

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