Diisopropylethylamine → tert-butyl 4-(3-(3-(3-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-3H-imidazo[4,5-b]pyridin-6-yl)-1,2,4-oxadiazol-5-yl)piperidine-1-carboxylate

HRID 706460

반응식

HRID 706460 반응식
[OH:1][N:2]=[C:3]([C:5]1[CH:6]=[C:7]2[N:13]=[CH:12][N:11]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][CH2:22][C:23]4[CH:24]=[N:25][C:26]([O:29][CH3:30])=[CH:27][CH:28]=4)=[C:17]([O:31][CH3:32])[CH:16]=3)[C:8]2=[N:9][CH:10]=1)[NH2:4].[C:33]([O:37][C:38]([N:40]1[CH2:45][CH2:44][CH:43]([C:46](O)=O)[CH2:42][CH2:41]1)=[O:39])([CH3:36])([CH3:35])[CH3:34].F[P-](F)(F)(F)(F)F.CN(C(N(C)C)=[N+]1C2C(=NC=CC=2)[N+]([O-])=N1)C.C(N(CC)C(C)C)(C)C>CN(C)C=O.C(OCC)(=O)C.[Cl-].[Na+].O>[CH3:32][O:31][C:17]1[CH:16]=[C:15]([CH:20]=[CH:19][C:18]=1[O:21][CH2:22][C:23]1[CH:24]=[N:25][C:26]([O:29][CH3:30])=[CH:27][CH:28]=1)[CH2:14][N:11]1[C:8]2=[N:9][CH:10]=[C:5]([C:3]3[N:4]=[C:46]([CH:43]4[CH2:44][CH2:45][N:40]([C:38]([O:37][C:33]([CH3:34])([CH3:36])[CH3:35])=[O:39])[CH2:41][CH2:42]4)[O:1][N:2]=3)[CH:6]=[C:7]2[N:13]=[CH:12]1

참가 물질

8

반응물 4

HCID 81531DiisopropylethylamineHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidHCID 131733011N'-hydroxy-3-(3-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-3H-imidazo[4,5-b]pyridine-6-carboximidamideHCID 178484293HCID 178484293, 화합물

생성물 1

HCID 118113979tert-butyl 4-(3-(3-(3-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-3H-imidazo[4,5-b]pyridin-6-yl)-1,2,4-oxadiazol-5-yl)piperidine-1-carboxylate수율 29.7%

시약·촉매·용매 3

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매HCID 57417360Sodium chloride; water용매

실험 절차

To a stirred solution of N′-hydroxy-3-(3-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-3H-imidazo[4,5-b]pyridine-6-carboximidamide (0.38 g, 0.75 mmol) in N,N-dimethylformamide (10 mL) was added 1-(tert-butoxycarbonyl)piperidine-4-carboxylic acid (0.21 g, 0.92 mmol), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (0.35 g, 0.92 mmol) and N,N-diisopropylethylamine (0.19 g, 1.50 mmol). The reaction mixture was stirred at room temperature. After 1 h, the mixture was diluted with ethyl acetate and brine. The organic phase was separated, dried over magnesium sulfate, filtered, and concentrated. The residue was dissolved in 1,4-dioxane (20 mL) and heated to 85° C. After 16 h, the reaction mixture was allowed to cool to room temperature and was concentrated. The crude product was purified by silica gel chromatography (2% methanol/dichloromethane elute) to provide 0.14 g (25%) of tert-butyl 4-(3-(3-(3-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-3H-imidazo[4,5-b]pyridin-6-yl)-1,2,4-oxadiazol-5-yl)piperidine-1-carboxylate as a yellow solid.

후처리

  1. customThe organic phase was separated
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in 1,4-dioxane (20 mL)
  6. temperatureheated to 85° C
  7. waitAfter 16 h
  8. temperatureto cool to room temperature
  9. concentrationwas concentrated
  10. customThe crude product was purified by silica gel chromatography (2% methanol/dichloromethane elute)

출처 및 근거

ORD 기록
ord-e8a558ae056e4b91947601873fff731b
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09174986B2

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