Lithium methanolate → 4-{3E-[5-(2-amino-phenylethynyl)-2,4-dimethoxyphenyl]acryloyl}-N-pyridin-2-yl-benzenesulfonamide

HRID 347380Notes

Reaction equation

HRID 347380 reaction equation
[C:1]([C:4]1[CH:9]=[CH:8][C:7]([S:10]([NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)(=[O:12])=[O:11])=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[NH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[C:27]#[C:28][C:29]1[C:30]([O:39][CH3:40])=[CH:31][C:32]([O:37][CH3:38])=[C:33]([CH:36]=1)[CH:34]=O.C[O-].[Li+]>CN(C=O)C.CO>[NH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[C:27]#[C:28][C:29]1[C:30]([O:39][CH3:40])=[CH:31][C:32]([O:37][CH3:38])=[C:33](/[CH:34]=[CH:2]/[C:1]([C:4]2[CH:5]=[CH:6][C:7]([S:10]([NH:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=3)(=[O:12])=[O:11])=[CH:8][CH:9]=2)=[O:3])[CH:36]=1

Participants

6

Reactant 3

HCID 4177230Lithium methanolateHCID 161156205-(2-Aminophenylethynyl)-2,4-dimethoxybenzaldehydeHCID 227503274-Acetyl-N-(2-pyridyl)benzenesulfonamide

Product 1

HCID 694901424-{3E-[5-(2-amino-phenylethynyl)-2,4-dimethoxyphenyl]acryloyl}-N-pyridin-2-yl-benzenesulfonamideYield 83.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

Ex-57A: A solution of 4-acetyl-N-pyridin-2-ylbenzenesulfonamide (Ex-5A, 451 mg, 1.63 mmol) and 5-(2-aminophenylethynyl)-2,4-dimethoxybenzaldehyde (Ex-35C, 459 mg, 1.63 mmol) in DMF (10.0 mL) and MeOH (5.0 mL) was treated with lithium methoxide (248 mg, 6.52 mmol). The reaction mixture was stirred at room temperature for 3 h under nitrogen, quenched with water (50 mL), and extracted with (3:1) ethyl acetate/THF (4×30 mL). The combined organic phase was brined, dried over sodium sulfate, and concentrated to a yellow oil. The crude material was purified by column chromatography (2–5% MeOH in dichloromethane) to give 735 mg (65%) of 4-{3E-[5-(2-amino-phenylethynyl)-2,4-dimethoxyphenyl]acryloyl}-N-pyridin-2-yl-benzenesulfonamide as a yellow oil. 1H-NMR (300 MHz, DMSO-d6) 8.21 (d, 2H, J=7.5), 8.18 (s, 1H), 8.00 (m, 4H), 7.81 (d, 1H, J=15.0 Hz), 7.74 (t, 2H, J=7.5 Hz), 7.17 (m, 2H), 7.05 (t, 2H, J=7.2 Hz), 6.80 (m, 3H), 6.52 (t, 1H), J=7.5 Hz), 5.43 (d, 1H, J=6.9 Hz), 3.96 (s, 3H), 3.95 (s, 3H).

Workup

  1. customquenched with water (50 mL)
  2. extractionextracted with (3:1) ethyl acetate/THF (4×30 mL)
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated to a yellow oil
  5. customThe crude material was purified by column chromatography (2–5% MeOH in dichloromethane)

Sources & evidence

ORD record
ord-a5f77c3e8eed4db997473cf8222fa2a1
Source dataset
uspto-grants-2007_02
Patent number
US07173129B2

Reaction notes

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