Potassium Carbonate → 6-Methyl-5-[(2'-methyl[2,4'-bipyridin]-4-yl)oxy]-2-pyridinamine

HRID 2278924Notes

Reaction equation

HRID 2278924 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[CH:11][C:12]([NH2:16])=[N:13][C:14]=2[CH3:15])[CH:5]=[CH:4][N:3]=1.[CH3:17][C:18]1[CH:23]=[C:22](B2OC(C)(C)C(C)(C)O2)[CH:21]=[CH:20][N:19]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.CCOC(C)=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>[CH3:15][C:14]1[N:13]=[C:12]([NH2:16])[CH:11]=[CH:10][C:9]=1[O:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([C:22]2[CH:21]=[CH:20][N:19]=[C:18]([CH3:17])[CH:23]=2)[CH:7]=1

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 164142742-Methylpyridine-4-boronic acid pinacol esterHCID 904029725-((2-Chloropyridin-4-yl)oxy)-6-methylpyridin-2-amine

Product 1

HCID 904035666-Methyl-5-[(2'-methyl[2,4'-bipyridin]-4-yl)oxy]-2-pyridinamineYield 71.8%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of Example A7 (905 mg, 3.84 mmol), 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (1.010 g, 4.61 mmol), potassium carbonate (1.592 g, 11.52 mmol) and tetrakis(triphenylphosphine)palladium(0) (222 mg, 0.192 mmol) in dioxane (16 mL) and water (4 mL) was degassed with Ar, sealed and warmed to 85° C. overnight. The mixture was cooled to RT, diluted with EtOAc (40 mL) and water (50 mL), and filtered through diatomaceous earth. The organic phase was separated and washed with brine (50 mL). The organic phase was diluted with methanol (5 mL), treated with SiliaMetS Thiol, (1.42 mmol/g, 4 g, 5.68 mmol), and gently stirred for 3 h. The mixture was filtered, washing the slica gel plug with 3% MeOH/EtOAc (2×10 mL). The filtrates were evaporated at reduced pressure and the residue was purified by silica gel chromatography (0-10% MeOH/EtOAc) to give 6-methyl-5-((2′-methyl-[2,4′-bipyridin]-4-yl)oxy)pyridin-2-amine as a tan solid (806 mg, 71%). 1H NMR (400 MHz, DMSO-d6): δ 9.07 (d, J=2.3 Hz, 1 H), 8.48 (d, J=5.7 Hz, 1 H), 8.25 (dd, J=8.1, 2.4 Hz, 1 H), 7.50 (d, J=2.4 Hz, 1 H), 7.33 (d, J=8.2 Hz, 1 H), 7.21 (d, J=8.7 Hz, 1 H), 6.67 (dd, J=5.7, 2.4 Hz, 1 H), 6.35 (d, J=8.7 Hz, 1 H), 5.96 (s, 2 H), 2.50 (s, 3 H), 2.08 (s, 3 H). MS (ESI) m/z: 293.2 (M+H+).

Workup

  1. customsealed
  2. temperatureThe mixture was cooled to RT
  3. filtrationfiltered through diatomaceous earth
  4. customThe organic phase was separated
  5. washwashed with brine (50 mL)
  6. additionThe organic phase was diluted with methanol (5 mL)
  7. filtrationThe mixture was filtered
  8. washwashing the slica gel plug with 3% MeOH/EtOAc (2×10 mL)
  9. customThe filtrates were evaporated at reduced pressure
  10. customthe residue was purified by silica gel chromatography (0-10% MeOH/EtOAc)

Sources & evidence

ORD record
ord-003effced3e04dafb827ccb7b0dba7dc
Source dataset
uspto-grants-2015_09
Patent number
US09133183B2

Reaction notes

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