2-(4-Acetylbenzenesulfonamido)acetic acid → (4-{3E-[5-(2-amino-phenylethynyl)-2,4-dimethoxyphenyl]acryloyl}benzenesulfonylamino)acetic acid

HRID 347372Notes

Reaction equation

HRID 347372 reaction equation
[C:1]([C:4]1[CH:9]=[CH:8][C:7]([S:10]([NH:13][CH2:14][C:15]([OH:17])=[O:16])(=[O:12])=[O:11])=[CH:6][CH:5]=1)(=[O:3])[CH3:2].C[O-].[Li+].[NH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[C:28]#[C:29][C:30]1[C:31]([O:40][CH3:41])=[CH:32][C:33]([O:38][CH3:39])=[C:34]([CH:37]=1)[CH:35]=O>CN(C=O)C.CO>[NH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[C:28]#[C:29][C:30]1[C:31]([O:40][CH3:41])=[CH:32][C:33]([O:38][CH3:39])=[C:34](/[CH:35]=[CH:2]/[C:1]([C:4]2[CH:9]=[CH:8][C:7]([S:10]([NH:13][CH2:14][C:15]([OH:17])=[O:16])(=[O:12])=[O:11])=[CH:6][CH:5]=2)=[O:3])[CH:37]=1

Participants

6

Reactant 3

HCID 21201292-(4-Acetylbenzenesulfonamido)acetic acidHCID 4177230Lithium methanolateHCID 161156205-(2-Aminophenylethynyl)-2,4-dimethoxybenzaldehyde

Product 1

HCID 69488015(4-{3E-[5-(2-amino-phenylethynyl)-2,4-dimethoxyphenyl]acryloyl}benzenesulfonylamino)acetic acidYield 36%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

Ex-51A: A solution (4-acetylbenzenesulfonylamino)acetic acid (Ex-26A, 238 mg, 1.01 mmol) in DMF (4.4 mL) and MeOH (1.9 mL) was treated with lithium methoxide (153 mg, 4.04 mmol), followed by the addition of 5-(2-amino-phenylethynyl)-2,4-dimethoxybenzaldehyde (Ex-35C, 300 mg, 1.07 mmol). The reaction mixture was stirred at room temperature for 23 h under nitrogen. It was quenched with water (10 mL) and extracted with ethyl acetate (25 mL). The aqueous phase was acidified with 6N HCl to pH3 and was extracted with (3:1) ethyl acetate/THF (5×25 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-dimethoxyphenyl]acryloyl}benzenesulfonylamino)acetic acid (188 mg, 36%) as an orange solid. 1H-NMR (300 MHz, DMSO-d6) 8.23 (d, 2H, J=8.7), 8.19 (s, 1H), 7.99 (d, 1H, J=15.9 Hz), 7.92 (d, 2H, J=7.80 Hz), 7.82 (d, 1H, J=16.5 Hz), 7.16 (d, 1H, J=6.6 Hz), 7.05 (t, 1H, J=8.1 Hz), 6.76 (s, 1H), 6.71 (d, 1H, J=7.8 Hz), 6.52 (t, 1H, J=7.2 Hz), 5.72 (s, 1H), 5.45 (br s, 1H), 3.96 (s, 3H), 3.95 (s, 3H), 3.41 (m, 2H).

Workup

  1. customIt was quenched with water (10 mL)
  2. extractionextracted with ethyl acetate (25 mL)
  3. extractionwas extracted with (3:1) ethyl acetate/THF (5×25 mL)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated to a yellow oil
  6. customThe crude material was purified by column chromatography (0–7.5% MeOH in dichloromethane)

Sources & evidence

ORD record
ord-2d7faa8e434e487da3e9d61158f502cc
Source dataset
uspto-grants-2007_02
Patent number
US07173129B2

Reaction notes

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