Sodium Bicarbonate → N-(tetrahydro-2H-pyran-4-ylmethyl)nicotinamide

HRID 579035Notizen

Reaktionsgleichung

BrC1C=NN([C:9]2[CH:24]=[CH:23][C:12]([C:13]([NH:15][CH2:16][CH:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[O:14])=[CH:11][N:10]=2)C=1OC.Cl.CN(C)C1C=C(B2OC(C)(C)C(C)(C)O2)C=CN=1.C(=O)(O)[O-].[Na+]>O1CCOCC1.O.CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[O:20]1[CH2:21][CH2:22][CH:17]([CH2:16][NH:15][C:13](=[O:14])[C:12]2[CH:23]=[CH:24][CH:9]=[N:10][CH:11]=2)[CH2:18][CH2:19]1

Komponenten

Reaktionsbedingungen

Temperatur: 110 °C

Versuchsvorschrift

Combined 6-(4-bromo-5-methoxy-1H-pyrazol-1-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)nicotinamide (80 mg, 0.202 mmol), N,N-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine hydrochloride (173 mg, 0.607 mmol), PdCl2(dppf)-CH2Cl2 adduct (16.53 mg, 0.020 mmol) and sodium bicarbonate (136 mg, 1.619 mmol) in dioxane (0.6 mL) and water (0.15 mL) was let stir for 15 min. The mixture was then capped and heated at 110° C. for 1 h in the microwave. Additional PdCl2(dppf)-CH2Cl2 adduct (17 mg) was then added and the heating continued at 110° C. for 1 h in the microwave. The reaction mixture was diluted with EtOAc, concentrated onto Celite® and purified on a 10 g NH silica gel column eluted with 10 to 100% EtOAc in hexanes to give 64442-(dimethylamino)pyridin-4-yl)-5-methoxy-1H-pyrazol-1-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)nicotinamide as a brown oil. MS m/z 437 [M+H]+.

Aufarbeitung

customThe mixture was then capped
concentrationconcentrated onto Celite®
custompurified on a 10 g NH silica gel column
washeluted with 10 to 100% EtOAc in hexanes

Quellen und Nachweise

ORD-Eintrag: ord-511ba6b85af54edda10ec18169d2fc7c
Quelldatensatz: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US09040522B2

Notizen zur Reaktion

Wird geladen…