Lithium methanolate → 4-[3E-(2,4-Dimethoxy-5-pyrrolidin-1-ylphenyl)acryloyl]-N-(3-imidazol-1-ylpropyl)benzenesulfonamide

HRID 347377Notes

Reaction equation

HRID 347377 reaction equation
[C:1]([C:4]1[CH:9]=[CH:8][C:7]([S:10]([NH:13][CH2:14][CH2:15][CH2:16][N:17]2[CH:21]=[CH:20][N:19]=[CH:18]2)(=[O:12])=[O:11])=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[CH3:22][O:23][C:24]1[CH:31]=[C:30]([O:32][CH3:33])[C:29]([N:34]2[CH2:38][CH2:37][CH2:36][CH2:35]2)=[CH:28][C:25]=1[CH:26]=O.C[O-].[Li+]>CN(C=O)C.CO>[CH3:22][O:23][C:24]1[CH:31]=[C:30]([O:32][CH3:33])[C:29]([N:34]2[CH2:38][CH2:37][CH2:36][CH2:35]2)=[CH:28][C:25]=1/[CH:26]=[CH:2]/[C:1]([C:4]1[CH:9]=[CH:8][C:7]([S:10]([NH:13][CH2:14][CH2:15][CH2:16][N:17]2[CH:21]=[CH:20][N:19]=[CH:18]2)(=[O:12])=[O:11])=[CH:6][CH:5]=1)=[O:3]

Participants

6

Reactant 3

HCID 4177230Lithium methanolateHCID 210825102,4-Dimethoxy-5-pyrrolidin-1-ylbenzaldehydeHCID 210825204-acetyl-N-(3-imidazol-1-ylpropyl)benzenesulfonamide

Product 1

HCID 113759074-[3E-(2,4-Dimethoxy-5-pyrrolidin-1-ylphenyl)acryloyl]-N-(3-imidazol-1-ylpropyl)benzenesulfonamideYield 41.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

A solution 4-acetyl-N-(3-imidazol-1-ylpropyl)benzenesulfonamide (Ex-23A, 653 mg, 2.13 mmol) and 2,4-dimethoxy-5-pyrrolidin-1-yl-benzaldehyde (Ex-38B, 500 mg, 2.13 mmol) in DMF (9.3 mL) and MeOH (4.0 mL) was treated with lithium methoxide (162 mg, 4.26 mmol) and stirred for 20 h at room temperature under nitrogen atmosphere. The reaction mixture was quenched with water (75 mL) and extracted ethyl acetate (3×50 mL). The organic phase was brined, dried over sodium sulfate, and concentrated to a red solid. Crystallization from hot ethanol (10 mL) and water (12 mL) gave 461 mg (41%) of the title compound as a red solid, mp 140–143° C. 1H-NMR (300 MHz, DMSO-d6) 8.23 (d, 2H, J=8.7 Hz), 8.05 (d, 1H, J=15.3 Hz), 7.88 (d, 2H, J=9.3 Hz), 7.64 (d, 1H, J=15.3 Hz), 7.51 (s, 1H), 7.17 (s, 1H), 7.05 (s, 1H), 6.81 (s, 1H), 6.67 (s, 1H), 3.92 (t, 2H, J=6.9 Hz), 3.86 (s, 6H), 3.15 (m, 4H), 2.68 (t, 2H, J=6.3 Hz), 1.80 (m, 6H). HRMS (ESI) Calcd. for C27H32N4O5S: 525.2172 (M+H)+; Found; 525.2179.

Workup

  1. customThe reaction mixture was quenched with water (75 mL)
  2. extractionextracted ethyl acetate (3×50 mL)
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated to a red solid
  5. customCrystallization from hot ethanol (10 mL) and water (12 mL)

Sources & evidence

ORD record
ord-b010bc1c4035441e9b3db89548bcc16d
Source dataset
uspto-grants-2007_02
Patent number
US07173129B2

Reaction notes

Loading…