Lithium methanolate → 4-{3E-[5-(2-amino-phenylethynyl)-2,4-dimethoxy-phenyl]acryloyl}-N-(3-imidazol-1-ylpropyl)benzenesulfonamide

HRID 347370Notes

Reaction equation

HRID 347370 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].[NH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[C:29]#[C:30][C:31]1[C:32]([O:41][CH3:42])=[CH:33][C:34]([O:39][CH3:40])=[C:35]([CH:38]=1)[CH:36]=O.C[O-].[Li+]>CN(C=O)C.CO>[NH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[C:29]#[C:30][C:31]1[C:32]([O:41][CH3:42])=[CH:33][C:34]([O:39][CH3:40])=[C:35](/[CH:36]=[CH:2]/[C:1]([C:4]2[CH:9]=[CH:8][C:7]([S:10]([NH:13][CH2:14][CH2:15][CH2:16][N:17]3[CH:21]=[CH:20][N:19]=[CH:18]3)(=[O:12])=[O:11])=[CH:6][CH:5]=2)=[O:3])[CH:38]=1

Participants

6

Reactant 3

HCID 4177230Lithium methanolateHCID 161156205-(2-Aminophenylethynyl)-2,4-dimethoxybenzaldehydeHCID 210825204-acetyl-N-(3-imidazol-1-ylpropyl)benzenesulfonamide

Product 1

HCID 694879324-{3E-[5-(2-amino-phenylethynyl)-2,4-dimethoxy-phenyl]acryloyl}-N-(3-imidazol-1-ylpropyl)benzenesulfonamideYield 53.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

Ex-50A: A solution of 4-acetyl-N-(3-imidazol-1-ylpropyl)benzenesulfonamide (Ex-23A, 312 mg, 1.02 mmol) and 5-(2-amino-phenylethynyl)-2,4-dimethoxybenzaldehyde (Ex-35C, 287 mg, 1.02 mmol) in DMF (4.4 mL) and MeOH (1.9 mL) was treated with lithium methoxide (155 mg, 4.08 mmol). The reaction mixture was stirred at room temperature for 16 h under nitrogen. The reaction mixture was quenched with water (25 mL) and extracted with (3:1) ethyl acetate/THF (3×25 mL). The organic phase was brined, dried over sodium sulfate, and concentrated to a yellow oil. The crude material was purified by column chromatography (0–7.5% MeOH in dichloromethane) to give 4-{3E-[5-(2-amino-phenylethynyl)-2,4-dimethoxy-phenyl]acryloyl}-N-(3-imidazol-1-ylpropyl)benzenesulfonamide (309 mg, 53%) as a yellow oil. 1H-NMR (3.00 MHz, DMSO-d6) 8.28 (d, 2H, J=7.80), 8.20 (s, 1H), 8.01 (d, 1H, J=15.0 Hz), 7.86 (m, 5 H), 7.51 (s, 1H), 7.16 (d, 1H, J=7.5 Hz), 7.23 (m, 2H), 6.79 (d, 2H, J=10.8 Hz), 6.72 (d, 1H, J=8.1 Hz), 6.52 (t, 1H, J=7.2 Hz), 5.45 (m, 1H), 3.97 (s, 3H), 3.96 (s, 3H), 3.92 (m, 4H), 1.77 (quintet, 2H, J=6.6 Hz).

Workup

  1. customThe reaction mixture was quenched with water (25 mL)
  2. extractionextracted with (3:1) ethyl acetate/THF (3×25 mL)
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated to a yellow oil
  5. customThe crude material was purified by column chromatography (0–7.5% MeOH in dichloromethane)

Sources & evidence

ORD record
ord-48e33402d44340d390e4c51dfc54433c
Source dataset
uspto-grants-2007_02
Patent number
US07173129B2

Reaction notes

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