Potassium Carbonate → N-(5-((6'-methyl-[2,3'-bipyridin]-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide

HRID 2279003Notes

Reaction equation

HRID 2279003 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]=[CH:41][C:40](B2OC(C)(C)C(C)(C)O2)=[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[N:38]=[CH:39][C:40]([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:41][CH:42]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 164142722-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 90426999N-(5-((2-chloropyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide

Product 1

HCID 86268609N-(5-((6'-methyl-[2,3'-bipyridin]-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamideYield 52%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
95 °C

Procedure

A mixture of Example C1 (0.200 g, 0.479 mmol), K2CO3 (0.132 g, 0.957 mmol) and 2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.126 g, 0.574 mmol) in dioxane (8 mL) and water (2 mL) was sparged with Ar, treated with Pd(PPh3)4 (0.055 g, 0.048 mmol), sparged again with Ar and heated at 95° C. overnight. 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, suspended in MeCN and sonicated. The resulting solid was collected via filtration and dried to afford N-(5-((6′-methyl-[2,3′-bipyridin]-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (118 mg, 52%). 1H NMR (400 MHz, DMSO-d6): δ 10.97 (s, 1 H), 9.09 (d, J=2.3 Hz, 1 H), 8.54 (d, J=5.7 Hz, 1 H), 8.29-8.24 (m, 2 H), 8.07 (d, J=9.0 Hz, 1 H), 7.75 (dd, J=9.0, 2.9 Hz, 1 H), 7.63 (d, J=2.4 Hz, 1 H), 7.33 (d, J=8.2 Hz, 1 H), 6.87 (dd, J=5.7, 2.4 Hz, 1 H), 3.92-3.77 (m, 5 H), 3.48-3.34 (m, 4 H), 2.50 (s, 3 H), 1.77-1.65 (m, 2 H), 1.62-1.55 (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. customsonicated
  8. filtrationThe resulting solid was collected via filtration
  9. customdried

Sources & evidence

ORD record
ord-76bdfa1ed6924a66aafc61689eb94db3
Source dataset
uspto-grants-2015_09
Patent number
US09133183B2

Reaction notes

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