Sodium Carbonate → 5-(6-acetamidopyridin-2-yl)-2-chloro-N-(3-cyano-1-phenyl-1H-pyrazol-5-yl)benzamide

HRID 522101노트

반응식

HRID 522101 반응식
[Cl:1][C:2]1[CH:23]=[CH:22][C:21](B2OC(C)(C)C(C)(C)O2)=[CH:20][C:3]=1[C:4]([NH:6][C:7]1[N:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[N:10]=[C:9]([C:18]#[N:19])[CH:8]=1)=[O:5].Br[C:34]1[N:39]=[C:38]([NH:40][C:41](=[O:43])[CH3:42])[CH:37]=[CH:36][CH:35]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.C(OCC)(=O)C.O.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:41]([NH:40][C:38]1[N:39]=[C:34]([C:21]2[CH:22]=[CH:23][C:2]([Cl:1])=[C:3]([CH:20]=2)[C:4]([NH:6][C:7]2[N:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[N:10]=[C:9]([C:18]#[N:19])[CH:8]=2)=[O:5])[CH:35]=[CH:36][CH:37]=1)(=[O:43])[CH3:42]

참가 물질

8

반응물 3

HCID 10340Sodium CarbonateHCID 10353221N-(6-bromopyridin-2-yl)acetamideHCID 1238597502-chloro-N-(3-cyano-1-phenyl-1H-pyrazol-5-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide

생성물 1

HCID 1184971625-(6-acetamidopyridin-2-yl)-2-chloro-N-(3-cyano-1-phenyl-1H-pyrazol-5-yl)benzamide수율 46%

시약·촉매·용매 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매2회HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

반응 조건

온도
100 °C

실험 절차

To a solution of 2-chloro-N-(3-cyano-1-phenyl-1H-pyrazol-5-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (Preparation 7, 0.5 mmol) in dioxane (5 mL) was added N-(6-bromopyridin-2-yl)acetamide (118 mg, 0.55 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (41 mg, 0.05 mmol), sodium carbonate (183 mg, 1.72 mmol) and water (1 mL). The reaction was heated to 100° C. for 18 hours. The reaction was allowed to cool to room temperature and diluted with ethyl acetate (10 mL) and water (10 mL). The layers were separated and the aqueous phase extracted with ethyl acetate (3×10 mL). The combined organic extracts were dried over sodium sulphate and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with 40-50% ethyl acetate in heptanes to afford the title compound as a yellow solid (104 mg, 46%).

후처리

  1. temperatureto cool to room temperature
  2. customThe layers were separated
  3. extractionthe aqueous phase extracted with ethyl acetate (3×10 mL)
  4. dry with materialThe combined organic extracts were dried over sodium sulphate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel column chromatography
  7. washeluting with 40-50% ethyl acetate in heptanes

출처 및 근거

ORD 기록
ord-5f102ee65fb440878dfd0a77c54addde
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09328096B2

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