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

HRID 347376Notes

Reaction equation

HRID 347376 reaction equation
[C:1]([C:4]1[CH:9]=[CH:8][C:7]([S:10]([NH:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=2)(=[O:12])=[O:11])=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[CH3:21][O:22][C:23]1[CH:30]=[C:29]([O:31][CH3:32])[C:28]([N:33]2[CH2:37][CH2:36][CH2:35][CH2:34]2)=[CH:27][C:24]=1[CH:25]=O.C[O-].[Li+]>CN(C=O)C.CO>[CH3:21][O:22][C:23]1[CH:30]=[C:29]([O:31][CH3:32])[C:28]([N:33]2[CH2:37][CH2:36][CH2:35][CH2:34]2)=[CH:27][C:24]=1/[CH:25]=[CH:2]/[C:1]([C:4]1[CH:5]=[CH:6][C:7]([S:10]([NH:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=2)(=[O:12])=[O:11])=[CH:8][CH:9]=1)=[O:3]

Participants

6

Reactant 3

HCID 4177230Lithium methanolateHCID 163752244-acetyl-N-pyridin-2-ylmethylbenzenesulfonamideHCID 210825102,4-Dimethoxy-5-pyrrolidin-1-ylbenzaldehyde

Product 1

HCID 117525304-[3E-(2,4-Dimethoxy-5-pyrrolidin-1-ylphenyl)acryloyl]-N-pyridin-2-ylmethylbenzenesulfonamideYield 58%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

A solution 4-acetyl-N-pyridin-2-ylmethyl-benzenesulfonamide (Ex-53A, 617 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. The reaction mixture was quenched with water (20 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 (25 mL) and water (50 mL) gave the title compound as a red solid (626 mg, 58%), mp 112–116° C. 1H-NMR (300 MHz, DMSO-d6) 8.40 (m, 3H), 8.19 (d, 2H, J=9.0 Hz), 8.05 (d, 1H, J=15.9 Hz), 7.89 (d, 2H, J=9.0 Hz), 7.62 (m, 2H), 7.25 (dd, 1H, J=4.5, 5.7 Hz), 7.17 (s, 1H), 6.67 (s, 1H), 4.05 (d, 2H, J=5.7 Hz), 3.86 (s, 3H), 3.85 (s, 3H), 3.16 (br s, 4H), 1.82 (br s, 4H). HRMS (ESI) Calcd. for C27H29N3O5S: 508.1906 [(M+H)+]; Found: 508.1902.

Workup

  1. customThe reaction mixture was quenched with water (20 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 (25 mL) and water (50 mL)

Sources & evidence

ORD record
ord-46c3c092bcad414f8812985f4cb417a1
Source dataset
uspto-grants-2007_02
Patent number
US07173129B2

Reaction notes

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