Sodium hydride → (3R,4R)-tert-butyl 4-(4-((3-ethyl-4-(imidazo[1,2-a]pyridine-3-carboxamido)-1H-indazol-1-yl)methyl)-1H-pyrazol-1-yl)-3-fluoropiperidine-1-carboxylate

HRID 79316

Reaktionsgleichung

[NH:1]1[CH:5]=[C:4]([CH2:6][N:7]2[C:15]3[C:10](=[C:11]([NH:16][C:17]([C:19]4[N:23]5[CH:24]=[CH:25][CH:26]=[CH:27][C:22]5=[N:21][CH:20]=4)=[O:18])[CH:12]=[CH:13][CH:14]=3)[C:9]([CH2:28][CH3:29])=[N:8]2)[CH:3]=[N:2]1.[H-].[Na+].[F:32][C@H:33]1[C@@H:38](OS(C)(=O)=O)[CH2:37][CH2:36][N:35]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH2:34]1.CS(OC1CCN(C(OC(C)(C)C)=O)CC1)(=O)=O>CC(N(C)C)=O>[CH2:28]([C:9]1[C:10]2[C:15](=[CH:14][CH:13]=[CH:12][C:11]=2[NH:16][C:17]([C:19]2[N:23]3[CH:24]=[CH:25][CH:26]=[CH:27][C:22]3=[N:21][CH:20]=2)=[O:18])[N:7]([CH2:6][C:4]2[CH:5]=[N:1][N:2]([C@@H:38]3[CH2:37][CH2:36][N:35]([C:44]([O:46][C:47]([CH3:49])([CH3:48])[CH3:50])=[O:45])[CH2:34][C@H:33]3[F:32])[CH:3]=2)[N:8]=1)[CH3:29]

Komponenten

Reaktionsbedingungen

Temperatur: 80 °C

Versuchsvorschrift

To N-(1-((1H-pyrazol-4-yl)methyl)-3-ethyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide (40 mg, 0.10 mmol; prepared according to Example 21, Step A) in DMA (5 mL) was added sodium hydride (7.5 mg, 0.31 mmol) and a mixture (approximately 9:1) of (3R,4S)-tert-butyl 3-fluoro-4-(methylsulfonyloxy)piperidine-1-carboxylate (prepared as in WO 2008/124323) and tert-butyl 4-(methylsulfonyloxy)piperidine-1-carboxylate (62 mg). The reaction mixture was heated to 80° C. and stirred for 3 hours. The mixture was concentrated under reduced pressure and silica gel chromatography (DCM/MeOH 10:1) gave the product (21 mg).

Aufarbeitung

concentrationThe mixture was concentrated under reduced pressure and silica gel chromatography (DCM/MeOH 10:1)

Quellen und Nachweise

ORD-Eintrag: ord-6bd136d8a6234d6689f0761701fdf75a
Quelldatensatz: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US08841455B2

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