Sodium Carbonate → N-Cyclopropyl-N-(3'-fluoro-5'-methyl-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4-yl)-4-oxazol-5-yl-benzamide

HRID 68868

Reaktionsgleichung

Br[C:2]1[CH:3]=[C:4]([F:31])[C:5]([N:8]2[CH2:13][CH2:12][CH:11]([N:14]([CH:28]3[CH2:30][CH2:29]3)[C:15](=[O:27])[C:16]3[CH:21]=[CH:20][C:19]([C:22]4[O:26][CH:25]=[N:24][CH:23]=4)=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)=[N:6][CH:7]=1.[CH3:32]B(O)O.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1>[CH:28]1([N:14]([CH:11]2[CH2:12][CH2:13][N:8]([C:5]3[C:4]([F:31])=[CH:3][C:2]([CH3:32])=[CH:7][N:6]=3)[CH2:9][CH2:10]2)[C:15](=[O:27])[C:16]2[CH:21]=[CH:20][C:19]([C:22]3[O:26][CH:25]=[N:24][CH:23]=3)=[CH:18][CH:17]=2)[CH2:30][CH2:29]1

Komponenten

Reaktionsbedingungen

Temperatur: 80 °C

Versuchsvorschrift

A mixture of N-(5′-Bromo-3′-fluoro-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-yl)-N-cyclopropyl-4-oxazol-5-yl-benzamide (170 mg), methylboronic acid (126 mg), Na2CO3 solution (2 M; 385 μL), and Pd(PPh)4 (20 mg) in dioxane (3 mL) is stirred at 80° C. overnight under an argon atmosphere. Three more portions of methylboronic acid (42 mg each) as well as PdCl2[1,1′-bis(diphenylphosphino)-ferrocene]*CH2Cl2 complex (14 mg) are added successively over the next day until the conversion is complete. The reaction mixture is filtered through a pad of aluminium oxide and washed with dioxane. The filtrate is concentrated in vacuo and the residue is purified by preparative HPLC. LC (method 1): tR=1.15 min; Mass spectrum (ESI+): m/z=421 [M+H]+.

Aufarbeitung

filtrationThe reaction mixture is filtered through a pad of aluminium oxide
washwashed with dioxane
concentrationThe filtrate is concentrated in vacuo
customthe residue is purified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag: ord-d1b6e929e0b34774ba5d5ce8aa8c76dd
Quelldatensatz: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US08822471B2

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