1,4-Dioxane → HCID 86731665, compound

HRID 1504772Notes

Reaction equation

HRID 1504772 reaction equation
O1CCOCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH3:15][N:16]1[C:20](B2OC(C)(C)C(C)(C)O2)=[CH:19][CH:18]=[N:17]1.Br[C:31]1[N:36]=[C:35]([NH2:37])[CH:34]=[C:33]([CH3:38])[CH:32]=1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.O>[CH3:38][C:33]1[CH:32]=[C:31]([C:20]2[N:16]([CH3:15])[N:17]=[CH:18][CH:19]=2)[N:36]=[C:35]([NH2:37])[CH:34]=1

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 49129081-methyl-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 221765076-Bromo-4-methylpyridin-2-amine

Product 1

HCID 86731665HCID 86731665, compound

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

Dioxane (2.12 mL), water (0.24 mL), tribasic potassium phosphate (300 mg, 1.41 mmol), and 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (120 mg, 0.58 mmol) were added to 6-bromo-4-methylpyridin-2-amine (88 mg, 0.47 mmol) in a scintillation vial. The vial was purged with argon 3 times before PdCl2(dppf)-CH2Cl2 adduct (34 mg, 0.047 mmol) was added. The vial was purged 3 times with argon, sealed, and heated to 100° C. After 1.5 hours, the reaction was cooled to room temperature, filtered through CELITE (washed with dichloromethane), and diluted with water. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (0-70% acetone/hexanes, linear gradient) to afford 4-methyl-6-(1-methyl-1H-pyrazol-5-yl)pyridin-2-amine. MS ESI calc'd. for C10H13N4 [M+H]+ 189. found 189. 1H NMR (500 MHz, CDCl3) δ 7.46 (s, 1H), 6.77 (s, 1H), 6.48 (d, J=1.8 Hz, 1H), 6.30 (s, 1H), 4.15 (s, 3H), 2.28 (s, 3H).

Workup

  1. additionwas added
  2. customThe vial was purged 3 times with argon
  3. customsealed
  4. temperaturethe reaction was cooled to room temperature
  5. filtrationfiltered through CELITE (washed with dichloromethane)
  6. additiondiluted with water
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by silica gel chromatography (0-70% acetone/hexanes, linear gradient)

Sources & evidence

ORD record
ord-88743590f90046f68210f084060bb6d5
Source dataset
uspto-grants-2015_12
Patent number
US09216173B2

Reaction notes

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