Sodium Bicarbonate → 4-Chloro-N-[3-(3-cyano-4-fluorophenyl)prop-2-yn-1-yl]-N-(2,4-dimethoxybenzyl)-1H-pyrrole-2-carboxamide

HRID 1172793Notes

Reaction equation

HRID 1172793 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:7]([O:9]N2C(=O)CCC2=O)=O)[NH:5][CH:6]=1.[Cl-].[C:18]([C:20]1[CH:21]=[C:22]([C:27]#[C:28][CH2:29][NH2+:30][CH2:31][C:32]2[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][C:33]=2[O:40][CH3:41])[CH:23]=[CH:24][C:25]=1[F:26])#[N:19].C([O-])(O)=O.[Na+]>CC#N.O>[Cl:1][C:2]1[CH:3]=[C:4]([C:7]([N:30]([CH2:29][C:28]#[C:27][C:22]2[CH:23]=[CH:24][C:25]([F:26])=[C:20]([C:18]#[N:19])[CH:21]=2)[CH2:31][C:32]2[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][C:33]=2[O:40][CH3:41])=[O:9])[NH:5][CH:6]=1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 866334231-{[(4-Chloro-1H-pyrrol-2-yl)carbonyl]oxy}pyrrolidine-2,5-dioneHCID 866334243-(3-Cyano-4-fluorophenyl)-N-(2,4-dimethoxybenzyl)prop-2-yn-1-aminium chloride

Product 1

HCID 686870754-Chloro-N-[3-(3-cyano-4-fluorophenyl)prop-2-yn-1-yl]-N-(2,4-dimethoxybenzyl)-1H-pyrrole-2-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

A solution of F1 (1.5 eq), F2 (1 eq) and NaHCO3 (2.5 eq) in a mixture of CH3CN and H2O (20:1) was heated at reflux for 12 hrs and then the MeCN was removed under reduced pressure. The resulting residue was diluted with DCM, washed with 1N HCl solution (2×) and then with brine; dried (Na2SO4), filtered and concentrated under reduced pressure. The resulting residue was purified by Biotage system eluting with EtOAc/petrol ether to obtain the desired compound. MS (ES) C24H19ClFN3O3 requires: 451, found: 452 (M+H)+. 1H NMR (400 MHz, DMSOd6) δ: 11.92 (1H, br. S), 7.91 (1H, dd, J=6.2, 1.9 Hz), 7.78-7.71 (1H, m), 7.54 (1H, t, J=9.0 Hz), 7.17-7.11 (1H, m), 7.07-7.04 (1H, m), 6.62-6.57 (1H, m), 6.56-6.20 (2H, m), 4.75 (2H, br. S), 4.46 (2H, br. S), 3.81-3.72 (6H, m).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 12 hrs
  3. customthe MeCN was removed under reduced pressure
  4. additionThe resulting residue was diluted with DCM
  5. washwashed with 1N HCl solution (2×)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting residue was purified by Biotage system
  10. washeluting with EtOAc/petrol ether

Sources & evidence

ORD record
ord-4c7e8a7a49ef44dcaad2e870b23d20c4
Source dataset
uspto-grants-2010_11
Patent number
US07834015B2

Reaction notes

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