Potassium Carbonate → N-(5-((2-(1-ethyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide

HRID 2278974Notes

Reaction equation

HRID 2278974 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.[CH2:30]([N:32]1[CH:36]=[C:35](B2OC(C)(C)C(C)(C)O2)[CH:34]=[N:33]1)[CH3:31].C([O-])([O-])=O.[K+].[K+]>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.O1CCOCC1.O>[CH2:30]([N:32]1[CH:36]=[C:35]([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:34]=[N:33]1)[CH3:31]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 113790451-Ethyl-1H-pyrazole-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 86270032N-(5-((2-(1-ethyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamideYield 80%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
80 °C

Procedure

A mixture of Example C1 (0.15 g, 0.40 mmol), 1-ethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.088 g, 0.40 mmol), and K2CO3 (0.2 g, 1.44 mmol) in 4:1 dioxane/water (5 mL) was sparged with Ar, treated with Pd(PPh3)4 (0.040 g, 0.036 mmol), sparged again with Ar and heated at 80° C. overnight. The mixture was cooled to RT, treated with brine, extracted with EtOAc (2×) and the combined organics were dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM). The material was treated with Et2O, allowed to stand at RT and the resulting solid collected via filtration to afford N-(5-((2-(1-ethyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (137 mg, 80%). 1H NMR (400 MHz, DMSO-d6): δ 10.96 (s, 1 H), 8.37 (d, J=5.7 Hz, 1 H), 8.30 (s, 1 H), 8.23 (d, J=2.9 Hz, 1 H), 8.07 (d, J=9.0 Hz, 1 H), 7.97 (s, 1 H), 7.71 (dd, J=9.0, 2.9 Hz, 1 H), 7.24 (d, J=2.4 Hz, 1 H), 6.69 (dd, J=5.7, 2.4 Hz, 1 H), 4.13 (q, J=7.3 Hz, 2 H), 3.86 (m, 5 H), 3.40 (m, 4 H), 1.71 (m, 2 H), 1.59 (m, 2 H), 1.37 (t, J=7.3 Hz, 3 H); MS (ESI) m/z: 478.2 (M+H+).

Workup

  1. customsparged again with Ar
  2. temperatureThe mixture was cooled to RT
  3. additiontreated with brine
  4. extractionextracted with EtOAc (2×)
  5. dry with materialthe combined organics were dried over Na2SO4
  6. concentrationconcentrated to dryness
  7. custompurified via silica gel chromatography (MeOH/DCM)
  8. additionThe material was treated with Et2O
  9. customto stand at RT
  10. filtrationthe resulting solid collected via filtration

Sources & evidence

ORD record
ord-bd33a3eef8a04a63bc97d374ba635f52
Source dataset
uspto-grants-2015_09
Patent number
US09133183B2

Reaction notes

Loading…