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

HRID 60327Notes

Reaction equation

HRID 60327 reaction equation
[C:1]1([S:7]([N:10]2[C:14]3[CH:15]=[N:16][C:17]([C:32]#[N:33])=[C:18]([O:19][CH:20]4[CH2:25][CH2:24][N:23]([CH2:26][CH2:27][S:28]([CH3:31])(=[O:30])=[O:29])[CH2:22][CH2:21]4)[C:13]=3[C:12]3[CH:34]=[C:35](Br)[CH:36]=[N:37][C:11]2=3)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C>[Pd].ClCCl>[C:1]1([S:7]([N:10]2[C:14]3[CH:15]=[N:16][C:17]([C:32]#[N:33])=[C:18]([O:19][CH:20]4[CH2:21][CH2:22][N:23]([CH2:26][CH2:27][S:28]([CH3:31])(=[O:30])=[O:29])[CH2:24][CH2:25]4)[C:13]=3[C:12]3[CH:34]=[CH:35][CH:36]=[N:37][C:11]2=3)(=[O:9])=[O:8])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 2

HCID 8471TriethylamineHCID 583650969-Benzenesulfonyl-3-bromo-5-[1-(2-methanesulfonylethyl)-piperidin-4-yloxy]-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

Product 1

HCID 583651709-Benzenesulfonyl-5-[1-(2-methanesulfonylethyl)-piperidin-4-yloxy]-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrileYield 66.5%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 6344DichloromethaneSolvent

Procedure

A suspension of 9-benzenesulfonyl-3-bromo-5-[1-(2-methanesulfonyl-ethyl)-piperidin-4-yloxy]-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (245 mg, 0.39 mmol) and palladium on carbon (10 wt %, 50 mg) in industrial methylated spirits (5 mL), dichloromethane (5 mL), and triethylamine (3 mL) was stirred at ambient temperature under an atmosphere of hydrogen for 24 hours. 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, 0-50% ethyl acetate in dichloromethane) to afford the title compound as an off-white solid (140 mg, 65%). LCMS (Method C): RT=4.97 min, M+H+=400. 1H NMR (300 MHz, DMSO-d6): 9.49 (s, 1H), 8.76 (dd, J=4.8, 1.6 Hz, 1H), 8.63 (dd, J=7.9, 1.7 Hz, 1H), 8.25-8.24 (m, 2H), 7.76 (t, J=7.4 Hz, 1H), 7.64-7.63 (m, 3H), 4.76-4.75 (m, 1H), 3.26 (t, J=7.4 Hz, 2H obscured by solvent peak), 3.02 (s, 3H), 2.88 (d, J=11.3 Hz, 2H), 2.72 (t, J=6.8 Hz, 2H), 2.14-2.14 (m, 4H), 1.91-1.91 (m, 2H).

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, 0-50% ethyl acetate in dichloromethane)

Sources & evidence

ORD record
ord-05d08099f5bb46818e3795081ca9d370
Source dataset
uspto-grants-2016_09
Patent number
US09440976B2

Reaction notes

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