Water → 6-Methyl-5-((6'-methyl-[2,3'-bipyridin]-4-yl)oxy)pyridin-2-amine

HRID 2278899Notes

Reaction equation

HRID 2278899 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]=[CH:22][C:21](B2OC(C)(C)C(C)(C)O2)=[CH:20][N:19]=1.C([O-])([O-])=O.[K+].[K+].O>O1CCOCC1.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:21]2[CH:20]=[N:19][C:18]([CH3:17])=[CH:23][CH:22]=2)[CH:7]=1

Participants

8

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 164142722-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 904029725-((2-Chloropyridin-4-yl)oxy)-6-methylpyridin-2-amine

Product 1

HCID 904031556-Methyl-5-((6'-methyl-[2,3'-bipyridin]-4-yl)oxy)pyridin-2-amineYield 89%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of Example A7 (2.8 g, 11.88 mmol), 2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (3.38 g, 15.45 mmol) and K2CO3 (3.28 g, 23.76 mmol) in dioxane 48 mL) and water (12 mL) was sparged with Ar, treated with Pd(PPh3)4 (1.373 g, 1.188 mmol) and heated at 85° C. overnight. The mixture was cooled to RT, diluted with EtOAc, the solids removed via filtration through diatomaceous earth and the filtrate concentrated to dryness and purified via silica gel chromatography (MeOH/DCM). The material was treated with MeCN, the solid collected via filtration and re-purified via silica gel chromatography (MeOH/DCM) to afford 6-methyl-5-((6′-methyl-[2,3′-bipyridin]-4-yl)oxy)pyridin-2-amine (3.08 g, 89%). 1H NMR (400 MHz, DMSO-d6): δ 9.56 (d, J=2.4 Hz, 1 H), 8.96 (d, J=5.7 Hz, 1 H), 8.71 (dd, J=8.1, 2.4 Hz, 1 H), 7.86 (d, J=2.4 Hz, 1 H), 7.76 (d, J=8.1 Hz, 1 H), 7.66 (d, J=8.7 Hz, 1 H), 7.18 (dd, J=5.7, 2.4 Hz, 1 H), 6.94 (dd, J=8.6, 0.7 Hz, 1 H), 5.86 (s, 2 H), 2.97 (s, 3 H), 2.59 (s, 3 H); MS (ESI) m/z: 293.1 (M+H+).

Workup

  1. temperatureThe mixture was cooled to RT
  2. customthe solids removed via filtration through diatomaceous earth
  3. concentrationthe filtrate concentrated to dryness
  4. custompurified via silica gel chromatography (MeOH/DCM)
  5. additionThe material was treated with MeCN
  6. filtrationthe solid collected via filtration
  7. customre-purified via silica gel chromatography (MeOH/DCM)

Sources & evidence

ORD record
ord-2a6c479eae804d14ac1167e7e665a284
Source dataset
uspto-grants-2015_09
Patent number
US09133183B2

Reaction notes

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