Acrylic Acid → 1-{4-[4-(2,4-dichlorophenyl)-1H-pyrrole-2-carbonyl]piperazin-1-yl}prop-2-en-1-one

HRID 588840Notes

Reaction equation

HRID 588840 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:10]=[C:11]([C:14]([N:16]2[CH2:21][CH2:20][N:19]([C:22]([O:24]C(C)(C)C)=O)[CH2:18][CH2:17]2)=[O:15])[NH:12][CH:13]=1.Cl.CO.[C:32](O)(=O)[CH:33]=C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C>>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:10]=[C:11]([C:14]([N:16]2[CH2:17][CH2:18][N:19]([C:22](=[O:24])[CH:32]=[CH2:33])[CH2:20][CH2:21]2)=[O:15])[NH:12][CH:13]=1

Participants

6

Reactant 5

HCID 6581Acrylic AcidHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 21893726Hydrochloride methanolHCID 90460345tert-Butyl 4-(4-(2,4-dichlorophenyl)-1H-pyrrole-2-carbonyl)piperazine-1-carboxylate

Product 1

HCID 1176071431-{4-[4-(2,4-dichlorophenyl)-1H-pyrrole-2-carbonyl]piperazin-1-yl}prop-2-en-1-oneYield 27%

Procedure

The mixture of tert-butyl 4-(4-(2,4-dichlorophenyl)-1H-pyrrole-2-carbonyl)piperazine-1-carboxylate (270 mg, 0.64 mmol) in HCl/MeOH (20 mL, 57.2 mmol) was stirred for 1 h. The mixture was concentrated in vacuo and the residue was dissolved in DMF (5 mL). To this mixture, acrylic acid (50 mg, 0.7 mmol), BOP (437 mg, 0.72 mmol) and DIEA (248 mg, 1.92 mmol) were added. The reaction mixture was stirred at room temperature for 1 h. The mixture was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (dichloromethane/methanol=60:1) to afford the desired product (40 mg, 27% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ: 11.88 (s, 1H), 7.66-7.63 (m, 2H), 7.43 (m, 1H), 7.38 (s, 1H), 6.91 (s, 1H), 6.85-6.78 (m, 1H), 6.18-6.13 (dd, J=2.4, 12.4 Hz, 1H), 5.74-5.71 (dd, J=2.4, 10.4 Hz, 1H), 3.76 (s, 4H), 3.68-3.63 (m, 4H). ESI-MS m/z: 377.3 [M−H]−.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. dissolutionthe residue was dissolved in DMF (5 mL)
  3. stirringThe reaction mixture was stirred at room temperature for 1 h
  4. customThe mixture was partitioned between ethyl acetate and water
  5. washThe organic layer was washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash column chromatography on silica gel (dichloromethane/methanol=60:1)

Sources & evidence

ORD record
ord-274e2c1808cc4d3cae10235f3c19ad01
Source dataset
uspto-grants-2016_01
Patent number
US09227978B2

Reaction notes

Loading…