Cesium carbonate → 5-((6-(1-methyl-1H-pyrazol-4-yl)pyrimidin-4-yl)oxy)pyridin-2-amine

HRID 1049318Notes

Reaction equation

HRID 1049318 reaction equation
Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([O:8][C:9]2[CH:10]=[CH:11][C:12]([NH2:15])=[N:13][CH:14]=2)[CH: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.[Cs+].[Cs+]>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[N:7]=[CH:6][N:5]=[C:4]([O:8][C:9]3[CH:10]=[CH:11][C:12]([NH2:15])=[N:13][CH:14]=3)[CH:3]=2)[CH:19]=[N:18]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 904032395-((6-Chloropyrimidin-4-yl)oxy)pyridin-2-amine

Product 1

HCID 904033665-((6-(1-methyl-1H-pyrazol-4-yl)pyrimidin-4-yl)oxy)pyridin-2-amineYield 68%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
90 °C

Procedure

A mixture of 5-((6-chloropyrimidin-4-yl)oxy)pyridin-2-amine (0.50 g, 2.246 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.467 g, 2.246 mmol), and Cs2CO3 (1.463 g, 4.49 mmol) in dioxane/H2O (5:1, 6 mL) was sparged with argon, treated with Pd(PPh3)4 (0.260 g, 0.225 mmol), sparged again with argon and heated at 90° C. overnight. The mixture was cooled to RT, the solids removed via filtration, rinsed with dioxane and the filtrate concentrated to dryness. The material was treated with EtOAc, the solid collected via filtration, rinsed with EtOAc and H2O and dried to obtain product. The layers of the filtrate were separated, the organic layer washed with brine, dried over Na2SO4, concentrated to dryness, triturated with EtOAc and the solid collected via filtration and combined with the above-isolated product to afford 5-((6-(1-methyl-1H-pyrazol-4-yl)pyrimidin-4-yl)oxy)pyridin-2-amine (410 mg, 68%). 1H NMR (400 MHz, DMSO-d6): δ 8.60 (d, J=1.1 Hz, 1H), 8.44 (s, 1H), 8.12 (s, 1H), 7.78 (d, J=2.9 Hz, 1H), 7.30-7.25 (m, 2H), 6.48 (d, J=8.9 Hz, 1H), 5.94 (s, 2H), 3.88 (s, 3H); MS (ESI) m/z: 269.1 (M+H+).

Workup

  1. customwas sparged with argon
  2. customsparged again with argon
  3. temperatureThe mixture was cooled to RT
  4. customthe solids removed via filtration
  5. washrinsed with dioxane
  6. concentrationthe filtrate concentrated to dryness
  7. additionThe material was treated with EtOAc
  8. filtrationthe solid collected via filtration
  9. washrinsed with EtOAc and H2O
  10. customdried
  11. customto obtain product
  12. customThe layers of the filtrate were separated
  13. washthe organic layer washed with brine
  14. dry with materialdried over Na2SO4
  15. concentrationconcentrated to dryness
  16. customtriturated with EtOAc
  17. filtrationthe solid collected via filtration

Sources & evidence

ORD record
ord-11e5178a4465432c8c7d38abbfa4682b
Source dataset
uspto-grants-2016_07
Patent number
US09382228B2

Reaction notes

Loading…