Cesium carbonate → 5-Bromo-3-[5-(1-hydroxy-1-methyl-ethyl)-pyridin-2-ylamino]-1-methyl-1H-pyridin-2-one

HRID 2069734노트

반응식

HRID 2069734 반응식
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]([OH:11])([CH3:10])[CH3:9])=[CH:4][CH:3]=1.Br[C:13]1[C:14](=[O:21])[N:15]([CH3:20])[CH:16]=[C:17]([Br:19])[CH:18]=1.C([O-])([O-])=O.[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[Br:19][C:17]1[CH:18]=[C:13]([NH:1][C:2]2[CH:3]=[CH:4][C:5]([C:8]([OH:11])([CH3:9])[CH3:10])=[CH:6][N:7]=2)[C:14](=[O:21])[N:15]([CH3:20])[CH:16]=1

참가 물질

8

반응물 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 36143503,5-Dibromo-1-methylpyridin-2(1H)-oneHCID 594737712-(6-Aminopyridin-3-yl)propan-2-ol

생성물 1

HCID 594737935-Bromo-3-[5-(1-hydroxy-1-methyl-ethyl)-pyridin-2-ylamino]-1-methyl-1H-pyridin-2-one수율 60.3%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

반응 조건

온도
120 °C

실험 절차

In a flame-dried seal tube reaction vial, dissolve 2-(6-Amino-pyridin-3-yl)-propan-2-ol (530 mg, 3.484 mmol) in anhydrous Dioxane (13 mL). Then add 3,5-Dibromo-1-methyl-1H-pyridin-2-one (1.022 g, 3.83 mmol), Cs2CO3 (3.4 g, 10.45 mmol) and Xantphos (0.2 g, 0.3482 mmol). Bubble argon through for 15 min before adding Pd(OAc)2 (39 mg, 0.1742 mmol). The tube as sealed and heated to 120° C. Reaction was kept at that temperature for 6 hrs. Reaction was then diluted with EtOAc (10 mL) and filtered through celite. Filter cake was washed with EtOAc (3×10 mL). The combined filtrate was concentrated and purified on ISCO column with 5-10% MeOH in 1/1 EtOAC/Hexane to afford 5-Bromo-3-[5-(1-hydroxy-1-methyl-ethyl)-pyridin-2-ylamino]-1-methyl-1H-pyridin-2-one (710 mg, yield 60%) as green solid.

후처리

  1. customIn a flame-dried seal tube
  2. customreaction vial
  3. customThe tube as sealed
  4. customReaction
  5. customReaction
  6. filtrationfiltered through celite
  7. filtrationFilter cake
  8. washwas washed with EtOAc (3×10 mL)
  9. concentrationThe combined filtrate was concentrated
  10. custompurified on ISCO column with 5-10% MeOH in 1/1 EtOAC/Hexane

출처 및 근거

ORD 기록
ord-d6cc6ff042694801a73e352d2450de0e
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08299077B2

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