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

HRID 60322Notes

Reaction equation

HRID 60322 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[C:20]3[C:21]4[CH:36]=[C:35]([Br:37])[CH:34]=[N:33][C:22]=4[N:23]([S:24]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)(=[O:26])=[O:25])[C:19]=3[CH:18]=[N:17][C:16]=2[C:38]#[N:39])[CH2:10][CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>ClCCl>[C:27]1([S:24]([N:23]2[C:19]3[CH:18]=[N:17][C:16]([C:38]#[N:39])=[C:15]([O:14][CH:11]4[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]4)[C:20]=3[C:21]3[CH:36]=[C:35]([Br:37])[CH:34]=[N:33][C:22]2=3)(=[O:25])=[O:26])[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 583652284-(9-Benzenesulfonyl-3-bromo-6-cyano-9H-dipyrido[2,3-b;4',3'-d]pyrrol-5-yloxy)piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 670274629-benzenesulfonyl-3-bromo-5-(piperidin-4-yloxy)-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrileYield 84%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-(9-benzenesulfonyl-3-bromo-6-cyano-9H-dipyrido[2,3-b;4′,3′-d]pyrrol-5-yloxy)piperidine-1-carboxylic acid tert-butyl ester (12.6 g, 20.6 mmol) in dichloromethane (36 mL) was added TFA (36 mL). After 1 hour at ambient temperature the reaction mixture was concentrated in-vacuo and the residue partitioned between saturated aqueous sodium carbonate solution (800 mL) and dichloromethane (2 L). The organic phase was separated, dried (Na2SO4), filtered and evaporated in-vacuo to afford the title compound as an off-white solid (8.8 g, 84%) which was used without further purification. 1H NMR (300 MHz, DMSO-d6): 9.46 (s, 1H), 8.90 (d, J=2.3 Hz, 1H), 8.64 (d, J=2.3 Hz, 1H), 8.23-8.22 (m, 2H), 7.78 (t, J=7.4 Hz, 1H), 7.64 (t, J=7.8 Hz, 2H), 4.85-4.85 (m, 1H), 3.17 (s, 1H), 3.00 (dt, J=13.0, 4.1 Hz, 2H), 2.50-2.49 (m, 2H obscured by solvent peak), 2.15-1.97 (m, 2H), 1.75-1.75 (m, 2H).

Workup

  1. concentrationAfter 1 hour at ambient temperature the reaction mixture was concentrated in-vacuo
  2. customthe residue partitioned between saturated aqueous sodium carbonate solution (800 mL) and dichloromethane (2 L)
  3. customThe organic phase was separated
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated in-vacuo

Sources & evidence

ORD record
ord-fc50b18bd19546e1a419af24dc4978e8
Source dataset
uspto-grants-2016_09
Patent number
US09440976B2

Reaction notes

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