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

HRID 579035Notes

Reaction equation

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

Participants

Conditions

Temperature: 110 °C

Procedure

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]+.

Workup

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

Sources & evidence

ORD record: ord-511ba6b85af54edda10ec18169d2fc7c
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09040522B2

Reaction notes

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