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

HRID 1667772Notes

Reaction equation

HRID 1667772 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][CH2:30]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.[CH2:32]([N:34]([CH2:37]C)[CH2:35][CH3:36])[CH3:33].CS(Cl)(=O)=O.[Cl-].[NH4+:45]>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][CH2:30][N:45]5[CH2:36][CH2:35][N:34]([CH3:37])[CH2:32][CH2:33]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 8471TriethylamineHCID 25517Ammonium ChlorideHCID 31297Methanesulfonyl chlorideHCID 674454694-(3-Chloro-phenyl)-2-[6-(3-hydroxy-propoxy)-5-methoxy-benzoimidazol-1-yl]-thiazole-5-carboxylic acid amide

Product 1

HCID 462205294-(3-Chloro-phenyl)-2-{5-methoxy-6-[3-(4-methyl-piperazin-1-yl)-propoxy]-benzoimidazol-1-yl}thiazole-5-carboxylic acid amide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of 0.067 g (0.15 mmole) of 4-(3-chloro-phenyl)-2-[6-(3-hydroxy-propoxy)-5-methoxy-benzoimidazol-1-yl]-thiazole-5-carboxylic acid amide (I.42a), 0.036 g (0.36 mmole) of triethylamine and 2 mL of dimethylformamide at 0 degrees was added, 0.020 g (0.18 mmole) of methanesulfonyl chloride. The mixture was stirred 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 mL of N-methylpiperazine. The mixture was cooled, poured into 25 mL of water 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 (25:75) to give 0.026 g of 4-(3-chloro-phenyl)-2-{5-methoxy-6-[3-(4-methyl-piperazin-1-yl)-propoxy]-benzoimidazol-1-yl}thiazole-5-carboxylic acid amide (I.42) as a pink solid. MH+/Z=541

Workup

  1. additionwas added
  2. extractionextracted three times with 20 mL of ethyl acetate
  3. washThe combined organic extracts were washed three times with 25 mL of water
  4. dry with materialonce with 25 mL of saturated sodium bicarbonate solution, once with 25 mL of brine, dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. temperatureThe residue was heated at 80 degrees for 1 hour with 2 mL of dimethylformamide and 0.080 mL of N-methylpiperazine
  8. temperatureThe mixture was cooled
  9. additionpoured into 25 mL of water
  10. extractionextracted three times with 20 mL of ethyl acetate
  11. washThe combined organic extracts were washed three times with 25 mL of water
  12. dry with materialonce with 25 mL of saturated sodium bicarbonate solution, once with 25 mL of brine, dried over anhydrous magnesium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure
  15. customThe residue was purified by silica gel chromatography
  16. washeluting with methanol-dichloromethane (25:75)

Sources & evidence

ORD record
ord-130177754fc94a588d8dc98b540f1ba2
Source dataset
uspto-grants-2011_10
Patent number
US08044213B2

Reaction notes

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