Formic Acid → 2-[6-(4-Methyl-piperazin-1-ylmethyl)-benzoimidazol-1-yl]-4-(3-trifluoromethyl-phenyl)thiazole-5-carboxylic acid amide trifluoroacetic acid salt

HRID 1667796ノート

反応式

HRID 1667796 の反応式
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:10]=[CH:11][C:12]([N+:34]([O-])=O)=[C:13]([NH:15][C:16]3[S:17][C:18]([C:31]([NH2:33])=[O:32])=[C:19]([C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=4)[N:20]=3)[CH:14]=2)[CH2:4][CH2:3]1.[H][H].[CH:39]([OH:41])=[O:40]>[Pd]>[F:28][C:27]([F:30])([F:29])[C:39]([OH:41])=[O:40].[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:10]=[CH:11][C:12]3[N:34]=[CH:39][N:15]([C:16]4[S:17][C:18]([C:31]([NH2:33])=[O:32])=[C:19]([C:21]5[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=5)[N:20]=4)[C:13]=3[CH:14]=2)[CH2:4][CH2:3]1

参加物

5

反応物 3

HCID 284Formic AcidHCID 866428552-[5-(4-Methyl-piperazin-1-ylmethyl)-2-nitro-phenylamino]-4-(3-trifluoromethylphenyl)-thiazole-5-carboxylic acid amideHCID 178418361HCID 178418361、化合物

生成物 1

HCID 866428562-[6-(4-Methyl-piperazin-1-ylmethyl)-benzoimidazol-1-yl]-4-(3-trifluoromethyl-phenyl)thiazole-5-carboxylic acid amide trifluoroacetic acid salt

試薬・触媒・溶媒 1

HCID 23938Palladium触媒

実験手順

A mixture of 0.1244 g (0.239 mmole) of 2-[5-(4-methyl-piperazin-1-ylmethyl)-2-nitro-phenylamino]-4-(3-trifluoromethylphenyl)-thiazole-5-carboxylic acid amide (VI.48c), 0.1186 g of 10% palladium on carbon catalyst and 10.4 mL of 96% formic acid was stirred under one atmosphere of hydrogen for 16 hours. The mixture was filtered through diatomaceous earth and the filter pad was washed with tetrahydrofuran. The filtrate was concentrated under reduced pressure. The residue was purified by reverse phase silica gel chromatography, eluting with acetonitrile-water-trifluoroacetic acid (gradient 10:90:0.1-60:40:0.1) to give 0.0693 g of 2-[6-(4-methyl-piperazin-1-ylmethyl)-benzoimidazol-1-yl]-4-(3-trifluoromethyl-phenyl)thiazole-5-carboxylic acid amide trifluoroacetic acid salt (I.48a). This salt was partitioned between 10 mL of saturated sodium carbonate solution and 150 mL of ethyl acetate. The organic layer was washed with 15 mL of water, then 15 mL of brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give 0.0693 g of 2-[6-(4-methyl-piperazin-1-ylmethyl)-benzoimidazol-1-yl]-4-(3-trifluoromethyl-phenyl)thiazole-5-carboxylic acid amide (I.48) as a white solid. MH+/Z=501.

後処理

  1. filtrationThe mixture was filtered through diatomaceous earth
  2. washthe filter pad was washed with tetrahydrofuran
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. customThe residue was purified by reverse phase silica gel chromatography
  5. washeluting with acetonitrile-water-trifluoroacetic acid (gradient 10:90:0.1-60:40:0.1)

出典と根拠

ORDレコード
ord-b4e12ca1870045748eddb557c4eb77f4
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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