Hydrochloric Acid → 4-(3-Chlorophenyl)-2-{5-[2-(4-methyl-piperazin-1-yl)-ethyl]-2-nitro-phenylamino}-thiazole-5-carboxylic acid amide

HRID 1667696ノート

反応式

HRID 1667696 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:9]=[C:10]([NH:16][C:17]3[CH:22]=[C:21]([CH2:23][CH:24]=O)[CH:20]=[CH:19][C:18]=3[N+:26]([O-:28])=[O:27])[S:11][C:12]=2[C:13]([NH2:15])=[O:14])[CH:5]=[CH:6][CH:7]=1.[CH3:29][N:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].Cl>C(OCC)C.ClCCl.C(O)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:9]=[C:10]([NH:16][C:17]3[CH:22]=[C:21]([CH2:23][CH2:24][N:33]4[CH2:34][CH2:35][N:30]([CH3:29])[CH2:31][CH2:32]4)[CH:20]=[CH:19][C:18]=3[N+:26]([O-:28])=[O:27])[S:11][C:12]=2[C:13]([NH2:15])=[O:14])[CH:5]=[CH:6][CH:7]=1

参加物

8

反応物 4

HCID 313Hydrochloric AcidHCID 531671-MethylpiperazineHCID 5049666Sodium triacetoxyborohydrideHCID 866428124-(3-Chloro-phenyl)-2-[2-nitro-5-(2-oxo-ethyl)-phenylamino]-thiazole-5-carboxylic acid amide

生成物 1

HCID 866428134-(3-Chlorophenyl)-2-{5-[2-(4-methyl-piperazin-1-yl)-ethyl]-2-nitro-phenylamino}-thiazole-5-carboxylic acid amide

試薬・触媒・溶媒 3

HCID 176Acetic Acid溶媒HCID 3283Diethyl Ether溶媒HCID 6344Dichloromethane溶媒

実験手順

A mixture of 0.200 g (0.43 mmole) of 4-(3-chloro-phenyl)-2-[5(2,2-dimethoxy-ethyl)-2-nitro-phenylamino]-thiazole-5-carboxylic acid amide (VI.9a) and 3 mL of 96% formic acid was stirred at room temperature for 1 hour. The solution was poured into water and the resulting precipitate was collected by filtration, washed with water and air-dried to give 0.135 g of 4-(3-chloro-phenyl)-2-[2-nitro-5-(2-oxo-ethyl)-phenylamino]-thiazole-5-carboxylic acid amide (VI.9b) as an orange solid. A mixture of 0.135 g of 4-(3-chloro-phenyl)-2-[2-nitro-5-(2-oxo-ethyl)-phenylamino]-thiazole-5-carboxylic acid amide (VI.9b), 0.10 mL of N-methylpiperazine, 0.10 mL of glacial acetic acid, 0.50 g of sodium triacetoxyborohydride and 10 mL of dichloromethane was stirred at room temperature for 16 hours. To the mixture was carefully added 1 mL of 1M hydrochloric acid and stirring was continued at room temperature for 30 minutes. The mixture was partitioned between 30 mL of dichloromethane and 30 mL of saturated aqueous sodium bicarbonate solution. The organic layer was washed once with 30 mL of water, then 30 mL of brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with methanol-dichloromethane (gradient 15:85-20:80) to give an orange foam. Trituration with diethyl ether gave 0.100 g of 4-(3-chlorophenyl)-2-{5-[2-(4-methyl-piperazin-1-yl)-ethyl]-2-nitro-phenylamino}-thiazole-5-carboxylic acid amide (VI.9c) as an orange solid.

後処理

  1. stirringstirring
  2. waitwas continued at room temperature for 30 minutes
  3. customThe mixture was partitioned between 30 mL of dichloromethane and 30 mL of saturated aqueous sodium bicarbonate solution
  4. washThe organic layer was washed once with 30 mL of water
  5. dry with material30 mL of brine, dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel chromatography
  9. washeluting with methanol-dichloromethane (gradient 15:85-20:80)
  10. customto give an orange foam

出典と根拠

ORDレコード
ord-686b11932f8b4c4692b4d5c51a90f2cf
出典データセット
uspto-grants-2011_10
特許番号
US08044213B2

反応ノート

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