Water → N-(5-chloropyridin-2-yl)-2-[((4-((methylamino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-5-chlorobenzamide

HRID 844173Notes

Reaction equation

HRID 844173 reaction equation
[CH3:1][NH2:2].[Cl:3][C:4]1[CH:5]=[CH:6][C:7]([NH:10][C:11](=[O:30])[C:12]2[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:13]=2[NH:19][C:20]([C:22]2[S:23][CH:24]=[C:25]([CH2:28]Cl)[C:26]=2[Cl:27])=[O:21])=[N:8][CH:9]=1.O>CN(C=O)C>[Cl:3][C:4]1[CH:5]=[CH:6][C:7]([NH:10][C:11](=[O:30])[C:12]2[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:13]=2[NH:19][C:20]([C:22]2[S:23][CH:24]=[C:25]([CH2:28][NH:2][CH3:1])[C:26]=2[Cl:27])=[O:21])=[N:8][CH:9]=1

Participants

5

Reactant 3

HCID 962WaterHCID 6329MethylamineHCID 16733272N-(5-chloropyridin-2-yl)-2-[((4-(chloromethyl)-3-chlorothiophen-2-yl)carbonyl)amino]-5-chlorobenzamide

Product 1

HCID 18376674N-(5-chloropyridin-2-yl)-2-[((4-((methylamino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-5-chlorobenzamideYield 38%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To methylamine (2.0 M in tetrahydrofuran, 16 mL, 32 mmol) was added a solution of N-(5-chloropyridin-2-yl)-2-[((4-(chloromethyl)-3-chlorothiophen-2-yl)carbonyl)amino]-5-chlorobenzamide (3.0 g, 6.3 mmol) in DMF (10 mL) and the mixture stirred at ambient temperature. After 4 hours the reaction mixture was poured into water (100 mL), concentrated in vacuo to remove the tetrahydrofuran and extracted with ethyl acetate (2×75 mL). The combined organics were washed with brine (75 mL), dried over MgSO4 and concentrated of all volatiles in vacuo. Purification by flash chromatography on silica gel afforded 1.1 g (38% yield) of N-(5-chloropyridin-2-yl)-2-[((4-((methylamino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-5-chlorobenzamide as a yellow solid; NMR (DMSO-d6/TFA) 11.4 (s, 1), 11.0 (s, 1), 8.9 (br s, 2), 7.6-8.4 (m, 7), 4.2 (m, 2), 2.6 (m, 3) ppm.

Workup

  1. concentrationconcentrated in vacuo
  2. customto remove the tetrahydrofuran
  3. extractionextracted with ethyl acetate (2×75 mL)
  4. washThe combined organics were washed with brine (75 mL)
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated of all volatiles in vacuo
  7. customPurification by flash chromatography on silica gel

Sources & evidence

ORD record
ord-f6d6573a32584039948d7348378783d8
Source dataset
uspto-grants-2002_04
Patent number
US06380221B1

Reaction notes

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