Potassium Carbonate → N-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)acetamide

HRID 1049235노트

반응식

HRID 1049235 반응식
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[CH:11][C:12]([NH:16][C:17](=[O:19])[CH3:18])=[N:13][C:14]=2[CH3:15])[CH:5]=[CH:4][N:3]=1.C([O-])([O-])=O.[K+].[K+].[CH3:26][N:27]1[CH:31]=[C:30](B2OC(C)(C)C(C)(C)O2)[CH:29]=[N:28]1>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>[CH3:15][C:14]1[N:13]=[C:12]([NH:16][C:17](=[O:19])[CH3:18])[CH:11]=[CH:10][C:9]=1[O:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([C:30]2[CH:29]=[N:28][N:27]([CH3:26])[CH:31]=2)[CH:7]=1

참가 물질

7

반응물 3

HCID 11430Potassium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 90402585N-(5-((2-chloropyridin-4-yl)oxy)-6-methylpyridin-2-yl)acetamide

생성물 1

HCID 90403222N-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)acetamide수율 87%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매2회HCID 312751,4-Dioxane용매

반응 조건

온도
80 °C

실험 절차

A solution of Example A5 (3.83 g, 13.79 mmol) in dioxane (50 mL) was sparged with argon, treated with a solution of K2CO3 (3.81 g, 27.6 mmol) in H2O (10 mL), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (3.44 g, 16.55 mmol) and Pd(PPh3)4 (0.637 g, 0.552 mmol) and heated at 80° C. for 16 h. The mixture was cooled to RT, treated with H2O, extracted with EtOAc (2×) and the combined organics washed with H2O, then brine, dried over Na2SO4 and concentrated to dryness. The material was suspended in 3:2 EtOAc/Hex, sonicated and the resulting solid collected via filtration and dried. The filtrate was concentrated to dryness, purified via silica gel chromatography (MeOH/DCM) and combined with the isolated solid to afford N-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)acetamide (3.88 g, 87%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 10.60 (s, 1H), 8.34 (d, J=5.7 Hz, 1H), 8.25 (s, 1H), 8.01 (d, J=8.8 Hz, 1H), 7.95 (s, 1H), 7.57 (d, J=8.8 Hz, 1H), 7.17 (d, J=2.4 Hz, 1H), 6.58 (dd, J=5.7, 2.4 Hz, 1H), 3.84 (s, 3H), 2.25 (s, 3H), 2.08 (s, 3H); MS (ESI) m/z: 324.1 (M+H+).

후처리

  1. temperatureThe mixture was cooled to RT
  2. extractionextracted with EtOAc (2×)
  3. washthe combined organics washed with H2O
  4. dry with materialbrine, dried over Na2SO4
  5. concentrationconcentrated to dryness
  6. customsonicated
  7. filtrationthe resulting solid collected via filtration
  8. customdried
  9. concentrationThe filtrate was concentrated to dryness
  10. custompurified via silica gel chromatography (MeOH/DCM)

출처 및 근거

ORD 기록
ord-f8ac2a82d6474b3b9d59c51842ad34dd
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09382228B2

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