Acetonitrile → 4-bromo-3-(1,2-dimethylindolin-6-yl)-1-methyl-1H-pyrrolo[2,3-b]pyridine

HRID 331020노트

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HRID 331020 반응식
[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([CH3:12])[CH:9]=[C:10](I)[C:3]=12.[CH3:13][N:14]1[C:22]2[C:17](=[CH:18][CH:19]=[C:20](B3OC(C)(C)C(C)(C)O3)[CH:21]=2)[CH2:16][CH:15]1[CH3:32].C(=O)([O-])[O-].[Na+].[Na+].C(#N)C>CN(C=O)C.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([CH3:12])[CH:9]=[C:10]([C:20]3[CH:21]=[C:22]4[C:17]([CH2:16][CH:15]([CH3:32])[N:14]4[CH3:13])=[CH:18][CH:19]=3)[C:3]=12

참가 물질

8

반응물 4

HCID 6342AcetonitrileHCID 10340Sodium CarbonateHCID 710901484-bromo-3-iodo-1-methyl-1H-pyrrolo[2,3-b]pyridineHCID 710901551,2-Dimethyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indoline

생성물 1

HCID 711145544-bromo-3-(1,2-dimethylindolin-6-yl)-1-methyl-1H-pyrrolo[2,3-b]pyridine수율 46.8%

시약·촉매·용매 3

HCID 6102075Dichlorobis(triphenylphosphine)palladium촉매HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

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온도
70 °C

실험 절차

4-Bromo-3-iodo-1-methyl-1H-pyrrolo[2,3-b]pyridine (D7) (1.1 g, 3.26 mmol), 1,2-dimethyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indoline (970 mg, 3.55 mmol), bis(triphenylphosphine) palladium(II) chloride (0.229 g, 0.326 mmol) and 2M sodium carbonate aqueous solution (16.32 mL, 32.6 mmol) were suspended in DMF (10 mL), ACN (10 mL) and DCM (5 mL). This was degassed under nitrogen for 10 mins before being heated to 70° C. and left stirring at this temperature for 30 mins. The reaction mixture was partitioned between ethyl acetate/water (ca. 40 mL each). The aqueous layer was separated and extracted with ethyl acetate (ca. 25 mL twice). The combined organic layer were dried over MgSO4 and concentrated. The residue was purified using chromatography on silica, eluting with a gradient of 0-40% ethyl acetate in cyclohexane to afford title compound (544 mg). LCMS (A): m/z (M+H)+ 356/358, C18H18BrN3 requires 355/357 (acidic).

후처리

  1. customThis was degassed under nitrogen for 10 mins
  2. waitleft
  3. customThe reaction mixture was partitioned between ethyl acetate/water (ca. 40 mL each)
  4. customThe aqueous layer was separated
  5. extractionextracted with ethyl acetate (ca. 25 mL twice)
  6. dry with materialThe combined organic layer were dried over MgSO4
  7. concentrationconcentrated
  8. customThe residue was purified
  9. washeluting with a gradient of 0-40% ethyl acetate in cyclohexane

출처 및 근거

ORD 기록
ord-2ea9e87a3a8b43ca8930b2a8f5dec91b
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08877742B2

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