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 1026588노트

반응식

HRID 1026588 반응식
[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

참가 물질

7

반응물 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

생성물 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)-one수율 69%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 21899815MeOH tetrahydrofuran용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-95ef784e0c7444bdb9fd29b3fc1a4f33
출처 데이터셋
uspto-grants-2014_05
특허 번호
US08729095B2

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