(1S)-(+)-Camphor-10-sulphonic acid → 1-[1-(2-Dimethylaminoethyl)piperidin-4-yl]-3-[4-(4-{3-[2-(4-fluorophenyl)acetyl]thioureido}phenoxy)pyridin-2-yl]-1-methylurea

HRID 492897ノート

反応式

HRID 492897 の反応式
[C@]12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.[NH2:16][C:17]1[CH:45]=[CH:44][C:20]([O:21][C:22]2[CH:27]=[CH:26][N:25]=[C:24]([NH:28][C:29](=[O:43])[N:30]([CH:32]3[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][N:40]([CH3:42])[CH3:41])[CH2:34][CH2:33]3)[CH3:31])[CH:23]=2)=[CH:19][CH:18]=1.[F:46][C:47]1[CH:52]=[CH:51][C:50]([CH2:53][C:54]([N:56]=[C:57]=[S:58])=[O:55])=[CH:49][CH:48]=1>C(O)C>[CH3:42][N:40]([CH3:41])[CH2:39][CH2:38][N:35]1[CH2:36][CH2:37][CH:32]([N:30]([CH3:31])[C:29]([NH:28][C:24]2[CH:23]=[C:22]([O:21][C:20]3[CH:19]=[CH:18][C:17]([NH:16][C:57]([NH:56][C:54](=[O:55])[CH2:53][C:50]4[CH:51]=[CH:52][C:47]([F:46])=[CH:48][CH:49]=4)=[S:58])=[CH:45][CH:44]=3)[CH:27]=[CH:26][N:25]=2)=[O:43])[CH2:33][CH2:34]1

参加物

5

反応物 3

HCID 218580(1S)-(+)-Camphor-10-sulphonic acidHCID 231531743-[4-(4-Aminophenoxy)pyridin-2-yl]-1-[1-(2-dimethylaminoethyl)piperidin-4-yl]-1-methylureaHCID 231532482-(4-Fluorophenyl)acetyl isothiocyanate

生成物 1

HCID 576774361-[1-(2-Dimethylaminoethyl)piperidin-4-yl]-3-[4-(4-{3-[2-(4-fluorophenyl)acetyl]thioureido}phenoxy)pyridin-2-yl]-1-methylurea収率 14.8%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

実験手順

After adding (1S)-(+)-10-camphorsulfonic acid (119 mg) to a solution of 3-[4-(4-aminophenoxy)pyridin-2-yl]-1-[1-(2-dimethylaminoethyl)piperidin-4-yl]-1-methylurea (121 mg) in ethanol (2.0 ml), the mixture was stirred for 10 minutes at room temperature. Next, 2-(4-fluorophenyl)acetyl isothiocyanate (2.34 ml, 0.25 M solution in toluene) was added thereto and the mixture was stirred at room temperature for 50 minutes. The reaction mixture was then partitioned between ethyl acetate and saturated aqueous sodium hydrogencarbonate. The organic layer was dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel column chromatography (Fuji Silysia NH, ethyl acetate, then ethyl acetate:methanol=20:1 to 10:1). Fractions containing the target compound were combined and concentrated. The residue was purified by LC-MS (eluent; acetonitrile-water-trifluoroacetic acid system). Fractions containing the target compound were concentrated, and saturated aqueous sodium hydrogencarbonate was added to the resultant residue. The mixture was extracted with ethyl acetate, and the organic layer was washed with brine and dried over anhydrous sodium sulfate. It was then concentrated to provide the title compound (26.3 mg, 14.8%) as white powder.

後処理

  1. stirringthe mixture was stirred at room temperature for 50 minutes
  2. customThe reaction mixture was then partitioned between ethyl acetate and saturated aqueous sodium hydrogencarbonate
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel column chromatography (Fuji Silysia NH, ethyl acetate
  6. additionFractions containing the target compound
  7. concentrationconcentrated
  8. customThe residue was purified by LC-MS (eluent; acetonitrile-water-trifluoroacetic acid system)
  9. additionFractions containing the target compound
  10. concentrationwere concentrated
  11. additionsaturated aqueous sodium hydrogencarbonate was added to the resultant residue
  12. extractionThe mixture was extracted with ethyl acetate
  13. washthe organic layer was washed with brine
  14. dry with materialdried over anhydrous sodium sulfate
  15. concentrationIt was then concentrated

出典と根拠

ORDレコード
ord-e7953e9f50694d0b85c2cf7a2a252102
出典データセット
uspto-grants-2009_05
特許番号
US07531532B2

反応ノート

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