Potassium Carbonate → N-(5-((2'-methyl-[2,4'-bipyridin]-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide

HRID 2279002Notes

Reaction equation

HRID 2279002 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[CH:11][C:12]([NH:15][C:16]([N:18]3[CH2:22][CH2:21][N:20]([CH:23]4[CH2:28][CH2:27][O:26][CH2:25][CH2:24]4)[C:19]3=[O:29])=[O:17])=[N:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1.C([O-])([O-])=O.[K+].[K+].[CH3:36][C:37]1[CH:42]=[C:41](B2OC(C)(C)C(C)(C)O2)[CH:40]=[CH:39][N:38]=1>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:36][C:37]1[CH:42]=[C:41]([C:2]2[CH:7]=[C:6]([O:8][C:9]3[CH:10]=[CH:11][C:12]([NH:15][C:16]([N:18]4[CH2:22][CH2:21][N:20]([CH:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[C:19]4=[O:29])=[O:17])=[N:13][CH:14]=3)[CH:5]=[CH:4][N:3]=2)[CH:40]=[CH:39][N:38]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 164142742-Methylpyridine-4-boronic acid pinacol esterHCID 90426999N-(5-((2-chloropyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide

Product 1

HCID 86268608N-(5-((2'-methyl-[2,4'-bipyridin]-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamideYield 20%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of Example C1 (0.250 g, 0.598 mmol), K2CO3 (0.165 g, 1.197 mmol) and 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.157 g, 0.718 mmol) in dioxane (8 mL) and water (2 mL) was sparged with Ar, treated with Pd(PPh3)4 (0.069 g, 0.060 mmol), sparged again with Ar and heated at 95° C. for 36 h. The mixture was cooled to RT, treated with satd. NaHCO3 and extracted with EtOAc (4×). The combined organics were dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM) to afford N-(5-((2′-methyl-[2,4′-bipyridin]-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (56 mg, 20%). 1H NMR (400 MHz, DMSO-d6): δ 10.98 (s, 1 H), 8.59 (d, J=5.6 Hz, 1 H), 8.52 (d, J=5.2 Hz, 1H), 8.27 (d, J=3.0 Hz, 1 H), 8.08 (d, J=9.1 Hz, 1 H), 7.89 (s, 1 H), 7.81-7.74 (m, 2 H), 7.70 (d, J=2.4 Hz, 1 H), 6.97 (dd, J=5.6, 2.4 Hz, 1 H), 3.93-3.78 (m, 5 H), 3.49-3.35 (m, 4 H), 2.52 (s, 3 H), 1.77-1.65 (m, 2 H), 1.62-1.56 (m, 2H); MS (ESI) m/z: 475.2 (M+H+).

Workup

  1. customsparged again with Ar
  2. temperatureThe mixture was cooled to RT
  3. additiontreated with satd
  4. extractionNaHCO3 and extracted with EtOAc (4×)
  5. dry with materialThe combined organics were dried over Na2SO4
  6. concentrationconcentrated to dryness
  7. custompurified via silica gel chromatography (MeOH/DCM)

Sources & evidence

ORD record
ord-7aa9543f17434818b5268f4e403d2bea
Source dataset
uspto-grants-2015_09
Patent number
US09133183B2

Reaction notes

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