Ammonium Chloride → 4-(3-Chloro-phenyl)-2-{5-methoxy-6-[2-(4-methyl-piperazin-1-yl)-ethoxy]-benzoimidazol-1-yl}thiazole-5-carboxylic acid amide

HRID 1667777Notes

Reaction equation

HRID 1667777 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:9]=[C:10]([N:16]3[C:20]4[CH:21]=[C:22]([O:27][CH2:28][CH2:29]O)[C:23]([O:25][CH3:26])=[CH:24][C:19]=4[N:18]=[CH:17]3)[S:11][C:12]=2[C:13]([NH2:15])=[O:14])[CH:5]=[CH:6][CH:7]=1.[CH2:31]([N:33]([CH:37](C)C)[CH:34](C)[CH3:35])[CH3:32].CS(Cl)(=O)=O.[Cl-].[NH4+:46]>O.CN(C)C=O>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:9]=[C:10]([N:16]3[C:20]4[CH:21]=[C:22]([O:27][CH2:28][CH2:29][N:46]5[CH2:35][CH2:34][N:33]([CH3:37])[CH2:31][CH2:32]5)[C:23]([O:25][CH3:26])=[CH:24][C:19]=4[N:18]=[CH:17]3)[S:11][C:12]=2[C:13]([NH2:15])=[O:14])[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 674458254-(3-Chloro-phenyl)-2-[6-(2-hydroxy-ethoxy)-5-methoxy-benzoimidazol-1-yl]-thiazole-5-carboxylic acid amide

Product 1

HCID 468320424-(3-Chloro-phenyl)-2-{5-methoxy-6-[2-(4-methyl-piperazin-1-yl)-ethoxy]-benzoimidazol-1-yl}thiazole-5-carboxylic acid amide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of 0.070 g (0.15 mmole) of 4-(3-chloro-phenyl)-2-[6-(2-hydroxy-ethoxy)-5-methoxy-benzoimidazol-1-yl]-thiazole-5-carboxylic acid amide (I.44a), 0.041 g (0.242 mmole) of ethyldiisopropylamine and 3 mL of dimethylformamide 0 degrees was added 0.027 g (0.24 mmole) of methanesulfonyl chloride. Stirring was continued for 1 hour and then 1 mL of saturated ammonium chloride solution was added dropwise. The mixture was poured into 25 mL of water and extracted three times with 20 mL of ethyl acetate. The combined organic extracts were washed three times with 25 mL of water, once with 25 mL of saturated sodium bicarbonate solution, once with 25 mL of brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was heated at 80 degrees for 1 hour with 2 mL of dimethylformamide and 0.080 g of N-methylpiperazine. The mixture was poured into 25 mL of water and extracted three times with 20 mL of ethyl acetate. The combined organic extracts were washed three times with 25 mL of water, once with 25 mL of saturated sodium bicarbonate solution, once with 25 mL of brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with methanol-dichloromethane (gradient 12:88-17:83) to give 0.023 g of 4-(3-chloro-phenyl)-2-{5-methoxy-6-[2-(4-methyl-piperazin-1-yl)-ethoxy]-benzoimidazol-1-yl}thiazole-5-carboxylic acid amide (I.44) as a pink solid. MH+/Z=527

Workup

  1. extractionextracted three times with 20 mL of ethyl acetate
  2. washThe combined organic extracts were washed three times with 25 mL of water
  3. dry with materialonce with 25 mL of saturated sodium bicarbonate solution, once with 25 mL of brine, dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. temperatureThe residue was heated at 80 degrees for 1 hour with 2 mL of dimethylformamide and 0.080 g of N-methylpiperazine
  7. additionThe mixture was poured into 25 mL of water
  8. extractionextracted three times with 20 mL of ethyl acetate
  9. washThe combined organic extracts were washed three times with 25 mL of water
  10. dry with materialonce with 25 mL of saturated sodium bicarbonate solution, once with 25 mL of brine, dried over anhydrous magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customThe residue was purified by silica gel chromatography
  14. washeluting with methanol-dichloromethane (gradient 12:88-17:83)

Sources & evidence

ORD record
ord-2caa2b242a1246ab97bc0582eb83c033
Source dataset
uspto-grants-2011_10
Patent number
US08044213B2

Reaction notes

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