Tetrahydrofuran → 7-chloro-1-{1-[(3-fluoro-2'-{[(1R)-3-hydroxy-1-methylpropyl]oxy}biphenyl-4-yl)carbonyl]piperidin-4-yl}-3,3-dimethyl-3,4-dihydro-1,5-naphthyridin-2(1H)-one

HRID 1026566ノート

反応式

HRID 1026566 の反応式
O1CCCC1.[Si]([O:23][CH2:24][CH2:25][C@H:26]([O:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[C:35]1[CH:40]=[CH:39][C:38]([C:41]([N:43]2[CH2:48][CH2:47][CH:46]([N:49]3[C:58]4[C:53](=[N:54][CH:55]=[C:56]([Cl:59])[CH:57]=4)[CH2:52][C:51]([CH3:61])([CH3:60])[C:50]3=[O:62])[CH2:45][CH2:44]2)=[O:42])=[C:37]([F:63])[CH:36]=1)[CH3:27])(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C(OCC)(=O)C>[Cl:59][C:56]1[CH:57]=[C:58]2[C:53]([CH2:52][C:51]([CH3:60])([CH3:61])[C:50](=[O:62])[N:49]2[CH:46]2[CH2:45][CH2:44][N:43]([C:41]([C:38]3[CH:39]=[CH:40][C:35]([C:30]4[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=4[O:28][C@H:26]([CH3:27])[CH2:25][CH2:24][OH:23])=[CH:36][C:37]=3[F:63])=[O:42])[CH2:48][CH2:47]2)=[N:54][CH:55]=1

参加物

5

反応物 3

HCID 8028Tetrahydrofuran2 回HCID 2724141Tetrabutylammonium FluorideHCID 680062751-{1-[(2'-{[(1R)-3-{[tert-butyl(diphenyl)silyl]oxy}-1-methylpropyl]oxy}-3-fluorobiphenyl-4-yl)carbonyl]piperidin-4-yl}-7-chloro-3,3-dimethyl-3,4-dihydro-1,5-naphthyridin-2(1H)-one

生成物 1

HCID 683151677-chloro-1-{1-[(3-fluoro-2'-{[(1R)-3-hydroxy-1-methylpropyl]oxy}biphenyl-4-yl)carbonyl]piperidin-4-yl}-3,3-dimethyl-3,4-dihydro-1,5-naphthyridin-2(1H)-one収率 80.9%

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

実験手順

To a tetrahydrofuran solution (11 ml) of 1-{1-[(2′-{[(1R)-3-{[tert-butyl(diphenyl)silyl]oxy}-1-methylpropyl]oxy}-3-fluorobiphenyl-4-yl)carbonyl]piperidin-4-yl}-7-chloro-3,3-dimethyl-3,4-dihydro-1,5-naphthyridin-2(1H)-one (525 mg) was added at room temperature a tetrahydrofuran solution (1 M, 1.28 ml) of tetrabutylammonium fluoride, followed by stirring for 3 hours. The reaction solution was diluted with ethyl acetate, washed sequentially with a saturated aqueous ammonium chloride solution and saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to afford 7-chloro-1-{1-[(3-fluoro-2′-{[(1R)-3-hydroxy-1-methylpropyl]oxy}biphenyl-4-yl)carbonyl]piperidin-4-yl}-3,3-dimethyl-3,4-dihydro-1,5-naphthyridin-2(1H)-one (301 mg).

後処理

  1. washwashed sequentially with a saturated aqueous ammonium chloride solution and saturated sodium chloride solution
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe resulting residue was purified by silica gel column chromatography

出典と根拠

ORDレコード
ord-51f2b013f8044678a597a206eeff365e
出典データセット
uspto-grants-2014_05
特許番号
US08729095B2

反応ノート

読み込み中…