Dimethyl Sulfoxide → N-(5-chloropyridin-2-yl)-2-[((4-(((diethylamino)oxy)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide

HRID 2300942Notes

Reaction equation

HRID 2300942 reaction equation
[CH2:1]([N:3]([CH2:5][CH3:6])[OH:4])[CH3:2].[Cl:7][C:8]1[CH:9]=[CH:10][C:11]([NH:14][C:15](=[O:36])[C:16]2[CH:21]=[C:20]([Cl:22])[CH:19]=[C:18]([O:23][CH3:24])[C:17]=2[NH:25][C:26]([C:28]2[S:29][CH:30]=[C:31]([CH2:34]Cl)[C:32]=2[Cl:33])=[O:27])=[N:12][CH:13]=1.CS(C)=O.C([O-])([O-])=O.[K+].[K+]>O>[Cl:7][C:8]1[CH:9]=[CH:10][C:11]([NH:14][C:15](=[O:36])[C:16]2[CH:21]=[C:20]([Cl:22])[CH:19]=[C:18]([O:23][CH3:24])[C:17]=2[NH:25][C:26]([C:28]2[S:29][CH:30]=[C:31]([CH2:34][O:4][N:3]([CH2:5][CH3:6])[CH2:1][CH3:2])[C:32]=2[Cl:33])=[O:27])=[N:12][CH:13]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 11430Potassium CarbonateHCID 19463DiethylhydroxylamineHCID 16731661HCID 16731661, compound

Product 1

HCID 18376699N-(5-chloropyridin-2-yl)-2-[((4-(((diethylamino)oxy)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
40 °C

Procedure

In a manner similar to that described in Paragraph J above, to a solution of N,N-diethylhydroxylamine (0.45 g, 5.0 mmol), N-(5-chloropyridin-2-yl)-2-[((4-(chloromethyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide (0.51 g, 1.0 mmol), and DMSO (10 mL) was added K2CO3 (0.68 g, 4.9 mmol). The mixture was stirred at 40° C. for 2 days, then it was poured into water. The resulting mixture was extracted with CH2Cl2 (2×50 mL). The organic layer was washed with 1% K2CO3, brine, treated with charcoal and concentrated. Purification by silica gel chromatography using 10:1 CH2Cl2:CH3OH with 1% NH4OH followed by precipitation from CH2Cl2 and hexane afforded N-(5-chloropyridin-2-yl)-2-[((4-(((diethylamino)oxy)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide, as a white solid; NMR (DMSO-d6) 8.35 (s, 1H), 8.20 (s, 1H), 8.10 (d, 1H), 7.90 (dd, 1H), 7.35 (s, 1H), 7.30 (s, 1H), 4.20 (s, 2H), 3.85 (s, 3H), 3.20-2.80 (m, 4H), 1.20 (t, 6H) ppm.

Workup

  1. extractionThe resulting mixture was extracted with CH2Cl2 (2×50 mL)
  2. washThe organic layer was washed with 1% K2CO3, brine
  3. additiontreated with charcoal
  4. concentrationconcentrated
  5. customPurification by silica gel chromatography
  6. customCH3OH with 1% NH4OH followed by precipitation from CH2Cl2 and hexane

Sources & evidence

ORD record
ord-80d93da5718c4d359a1a9ee9eacb5010
Source dataset
uspto-grants-2002_12
Patent number
US06498185B1

Reaction notes

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