Hydrochloric Acid → 3-Amino-4-{4-[3E-(5-benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-phenylamino}-cyclobut-3-ene-1,2-dione

HRID 10725Notes

Reaction equation

HRID 10725 reaction equation
[C:1]([C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]2[C:12](=[O:17])[C:13](=[O:16])[C:14]=2[NH2:15])=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[S:18]1[C:22]([C:23]2[C:24]([O:33][CH3:34])=[CH:25][C:26]([O:31][CH3:32])=[C:27]([CH:30]=2)[CH:28]=O)=[CH:21][C:20]2[CH:35]=[CH:36][CH:37]=[CH:38][C:19]1=2.O(C)[Li].Cl>CN(C=O)C>[NH2:15][C:14]1[C:13](=[O:16])[C:12](=[O:17])[C:11]=1[NH:10][C:7]1[CH:6]=[CH:5][C:4]([C:1](=[O:3])/[CH:2]=[CH:28]/[C:27]2[CH:30]=[C:23]([C:22]3[S:18][C:19]4[CH:38]=[CH:37][CH:36]=[CH:35][C:20]=4[CH:21]=3)[C:24]([O:33][CH3:34])=[CH:25][C:26]=2[O:31][CH3:32])=[CH:9][CH:8]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 161159165-Benzo[b]thiophen-2-yl-2,4-dimethoxy-benzaldehydeHCID 219810423-(4-Acetyl-phenylamino)-4-amino-cyclobut-3-ene-1,2-dioneHCID 178419045HCID 178419045, compound

Product 1

HCID 210416043-Amino-4-{4-[3E-(5-benzo[b]thiophen-2-yl-2,4-dimethoxy-phenyl)-acryloyl]-phenylamino}-cyclobut-3-ene-1,2-dioneYield 5.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3-(4-Acetyl-phenylamino)-4-amino-cyclobut-3-ene-1,2-dione (Ex-102A, 0.46 g, 2 mmol), and 5-(benzo[b]thien-2-yl)-2,4-dimethoxybenzaldehyde (Ex-3A, 0.596 g, 2 mmol) were dissolved in DMF (10 mL) under nitrogen, and 4.0 ml (4 mmol) of LiOMe (1.0 M in MeOH) was added. The mixture was stirred under nitrogen at room temperature over night. The reaction mixture was poured into ice-water, acidified to pH1 with 3N HCl, extracted with dichloromethane. The combined organic phase was then washed with brine and water, dried over MgSO4, column chromatography (5% MeOH in CH2Cl2) to give 57 mg (5.4%) title compound as a yellow solid, mp>260° C. 1H-NMR (DMSO-d6) δ 10.08 (s, 1H), 8.36 (s, 1H), 8.18 (d, J=8 Hz, 2H), 8.03 (d, J=15 Hz, 1H), 7.82–7.95 (m, 4H), 7.57 (d, J=8 Hz, 2H), 7.27–7.37 (m, 2H), 6.85 (s, 1H), 4.02 (s, 3H), 3.99 (s, 3H), 3.26 (s, 2H). MS m/z=511[M+H]+, (20%), 416 (100%). HRMS (ES+) Calcd. for C29H22N2O5S: 511.1327. Found: 511.1326.

Workup

  1. extractionextracted with dichloromethane
  2. washThe combined organic phase was then washed with brine and water
  3. dry with materialdried over MgSO4, column chromatography (5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-a3e8acc5c7b94478861d04fd87697f50
Source dataset
uspto-grants-2006_08
Patent number
US07094801B2

Reaction notes

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