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

HRID 1026588ノート

反応式

HRID 1026588 の反応式
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:18][C@H:19]([CH3:23])[CH2:20][CH2:21][OH:22])=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([C:14](O)=[O:15])=[C:10]([CH3:17])[CH:9]=2)[CH:7]=1.FC(F)(F)C(O)=O.[Cl:31][C:32]1[CH:41]=[C:40]2[C:35]([CH2:36][C:37]([CH3:50])([CH3:49])[C:38](=[O:48])[N:39]2[CH:42]2[CH2:47][CH2:46][NH:45][CH2:44][CH2:43]2)=[N:34][CH:33]=1.CN1CCOCC1.[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1>C(Cl)Cl.CO.O1CCCC1>[Cl:31][C:32]1[CH:41]=[C:40]2[C:35]([CH2:36][C:37]([CH3:50])([CH3:49])[C:38](=[O:48])[N:39]2[CH:42]2[CH2:43][CH2:44][N:45]([C:14]([C:11]3[CH:12]=[CH:13][C:8]([C:6]4[CH:7]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=4[O:18][C@H:19]([CH3:23])[CH2:20][CH2:21][OH:22])=[CH:9][C:10]=3[CH3:17])=[O:15])[CH2:46][CH2:47]2)=[N:34][CH:33]=1

参加物

7

反応物 4

HCID 79724-MethylmorpholineHCID 27340594-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chlorideHCID 680061317-chloro-3,3-dimethyl-1-piperidin-4-yl-3,4-dihydro-1,5-naphthyridin-2(1H)-one trifluoroacetateHCID 680063405'-fluoro-2'-{[(1R)-3-hydroxy-1-methylpropyl]oxy}-3-methylbiphenyl-4-carboxylic acid

生成物 1

HCID 680060717-chloro-1-{1-[(5'-fluoro-2'-{[(1R)-3-hydroxy-1-methylpropyl]oxy}-3-methylbiphenyl-4-yl)carbonyl]piperidin-4-yl}-3,3-dimethyl-3,4-dihydro-1,5-naphthyridin-2(1H)-one収率 69%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 21899815MeOH tetrahydrofuran溶媒

実験手順

To a methanol-tetrahydrofuran (1:1) mixed solvent solution (20.0 ml) of 5′-fluoro-2′-{[(1R)-3-hydroxy-1-methylpropyl]oxy}-3-methylbiphenyl-4-carboxylic acid (637 mg) and 7-chloro-3,3-dimethyl-1-piperidin-4-yl-3,4-dihydro-1,5-naphthyridin-2(1H)-one trifluoroacetate (Reference Example 10) (876 mg) were added at room temperature N-methylmorpholine (0.660 ml) and 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (940 mg), followed by stirring for 1 hour. The reaction solution was diluted with methylene chloride, then washed sequentially with water and saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography to afford 7-chloro-1-{1-[(5′-fluoro-2′-{[(1R)-3-hydroxy-1-methylpropyl]oxy}-3-methylbiphenyl-4-yl)carbonyl]piperidin-4-yl}-3,3-dimethyl-3,4-dihydro-1,5-naphthyridin-2(1H)-one (820 mg).

後処理

  1. washwashed sequentially with water 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 chromatography

出典と根拠

ORDレコード
ord-95ef784e0c7444bdb9fd29b3fc1a4f33
出典データセット
uspto-grants-2014_05
特許番号
US08729095B2

反応ノート

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