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

HRID 2278980Notes

Reaction equation

HRID 2278980 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+]>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>[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, 2.25 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.47 g, 2.25 mmol), and Cs2CO3 (1.46 g, 4.49 mmol) in 5:1 dioxane/water (6 mL) was sparged with Ar, treated with Pd(PPh3)4 (0.26 g, 0.23 mmol), sparged again with Ar and heated at 90° C. overnight. The mixture was cooled to RT, the solids removed via filtration, washed with dioxane and the filtrate concentrated to dryness. The residue was treated with water, extracted with EtOAc, washed with brine, dried over Na2SO4, and concentrated to dryness. The material was treated with EtOAc and the resulting solid collected via filtration to afford 5-((6-(1-methyl-1H-pyrazol-4-yl)pyrimidin-4-yl)oxy)pyridin-2-amine (0.41 g, 68%). 1H NMR (400 MHz, DMSO-d6): δ 8.60 (d, 1 H), 8.44 (s, 1 H), 8.12 (s, 1 H), 7.78 (d, 1 H), 7.28 (m, 2 H), 6.48 (d, 1 H), 5.94 (s, 2 H), 3.88 (s, 3 H); MS (ESI) m/z: 269.1 (M+H+).

Workup

  1. customwas sparged with Ar
  2. customsparged again with Ar
  3. temperatureThe mixture was cooled to RT
  4. customthe solids removed via filtration
  5. washwashed with dioxane
  6. concentrationthe filtrate concentrated to dryness
  7. additionThe residue was treated with water
  8. extractionextracted with EtOAc
  9. washwashed with brine
  10. dry with materialdried over Na2SO4
  11. concentrationconcentrated to dryness
  12. additionThe material was treated with EtOAc
  13. filtrationthe resulting solid collected via filtration

Sources & evidence

ORD record
ord-4e2880f48f3e4e9fa0d7932460140d17
Source dataset
uspto-grants-2015_09
Patent number
US09133183B2

Reaction notes

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