Potassium Carbonate → 5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyrimidin-2-amine

HRID 2278926Notes

Reaction equation

HRID 2278926 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[N:11][C:12]([NH2:15])=[N:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1.[CH3:16][N:17]1[CH:21]=[C:20](B2OC(C)(C)C(C)(C)O2)[CH:19]=[N:18]1.C(=O)([O-])[O-].[K+].[K+]>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>[CH3:16][N:17]1[CH:21]=[C:20]([C:2]2[CH:7]=[C:6]([O:8][C:9]3[CH:10]=[N:11][C:12]([NH2:15])=[N:13][CH:14]=3)[CH:5]=[CH:4][N:3]=2)[CH:19]=[N:18]1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 904034955-((2-Chloropyridin-4-yl)oxy)pyrimidin-2-amine

Product 1

HCID 904034835-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyrimidin-2-amineYield 55.8%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
85 °C

Procedure

5-((2-chloropyridin-4-yl)oxy)pyrimidin-2-amine (676 mg, 3.04 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (758 mg, 3.64 mmol), potassium carbonate (1.259 g, 9.11 mmol) and tetrakis(triphenylphosphine)palladium(0) (175 mg, 0.152 mmol) were combined in dioxane (12 mL) and water (3 mL). The mixture was degassed with argon, sealed and warmed to 85° C. overnight. The mixture was diluted with EtOAc (75 mL) and water (40 mL) and was filtered to collect an off-white solid. The organic phase was separated, washed with brine (40 mL) and evaporated at reduced pressure to give additional off-white solid. The two crops of solids were combined and triturated with EtOAc (15 mL) with sonication. The solid was collected by filtration, washed with EtOAc (2×5 mL) and dried under vacuum to provide 5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyrimidin-2-amine (455 mg, 55%). 1H NMR (DMSO-d6): δ 8.34 (d, J=5.7 Hz, 1 H), 8.26 (s, 1 H), 8.22 (s, 2 H), 7.96 (s, 1 H), 7.19 (d, J=2.4 Hz, 1 H), 6.77 (s, 2 H), 6.67 (dd, J=5.7, 2.5 Hz, 1 H), 3.84 (s, 3 H); MS (ESI) m/z: 269.1 (M+H+).

Workup

  1. customThe mixture was degassed with argon
  2. customsealed
  3. additionThe mixture was diluted with EtOAc (75 mL) and water (40 mL)
  4. filtrationwas filtered
  5. customto collect an off-white solid
  6. customThe organic phase was separated
  7. washwashed with brine (40 mL)
  8. customevaporated at reduced pressure
  9. customto give additional off-white solid
  10. customtriturated with EtOAc (15 mL) with sonication
  11. filtrationThe solid was collected by filtration
  12. washwashed with EtOAc (2×5 mL)
  13. customdried under vacuum

Sources & evidence

ORD record
ord-6c5cf6e236704fdf98e74fb1c12850e9
Source dataset
uspto-grants-2015_09
Patent number
US09133183B2

Reaction notes

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