Potassium Carbonate → 2-((6-methyl-4-(tetrahydro-2H-pyran-4-yl)pyridin-2-yl)amino)isonicotinonitrile

HRID 1057028Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[C:13]([C:15]#[N:16])[CH:12]=[CH:11][N:10]=2)[CH:5]=[C:4]([CH:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[CH:3]=1.[CH3:23]B(O)O.C(=O)([O-])[O-].[K+].[K+]>C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Fe]>[CH3:23][C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[C:13]([CH:12]=[CH:11][N:10]=2)[C:15]#[N:16])[CH:5]=[C:4]([CH:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[CH:3]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A vial was charged with 2-[(6-chloro-4-tetrahydropyran-4-yl-2-pyridyl)amino]pyridine-4-carbonitrile (51.1 mg, 0.162 mmol), [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (13.5 mg, 10 mol %), methylboronic acid (20.0 mg, 0.325 mmol), and potassium carbonate (68 mg, 0.49 mmol) and purged under nitrogen before the addition of degassed 1,4-dioxane (1.6 mL) and degassed water (0.5 mL). The mixture was stirred at 100° C. for 19 hr and then diluted with CH2Cl2, filtered through Celite and washed with brine. The organics were dried over MgSO4 and concentrated to dryness. The reaction residue thus obtained was purified by RPLC to afford 2-((6-methyl-4-(tetrahydro-2H-pyran-4-yl)pyridin-2-yl)amino)isonicotinonitrile as a white solid (4.1 mg, 9%); ESI-LRMS m/z [M+1]+=295.

Workup

custompurged under nitrogen before the addition of degassed 1,4-dioxane (1.6 mL)
customdegassed water (0.5 mL)
additiondiluted with CH2Cl2
filtrationfiltered through Celite
washwashed with brine
dry with materialThe organics were dried over MgSO4
concentrationconcentrated to dryness
customThe reaction residue thus obtained
customwas purified by RPLC

Sources & evidence

ORD record: ord-f8571fe90a7e4f1ebacfd68d05be7f97
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09399636B2

Reaction notes

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