Sodium Carbonate → 4-bromo-1-isopropyl-3-(1-methylindolin-6-yl)-1H-pyrrolo[2,3-b]pyridine

HRID 330997노트

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HRID 330997 반응식
[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([CH3:14])[CH3:13])[CH:9]=[C:10](I)[C:3]=12.[CH3:15][N:16]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22](B3OC(C)(C)C(C)(C)O3)[CH:23]=2)[CH2:18][CH2:17]1.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.CN(C=O)C.C(Cl)Cl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([CH3:14])[CH3:13])[CH:9]=[C:10]([C:22]3[CH:23]=[C:24]4[C:19]([CH2:18][CH2:17][N:16]4[CH3:15])=[CH:20][CH:21]=3)[C:3]=12

참가 물질

8

반응물 3

HCID 10340Sodium CarbonateHCID 709799671-Methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indolineHCID 710903694-bromo-3-iodo-1-isopropyl-1H-pyrrolo[2,3-b]pyridine

생성물 1

HCID 710903934-bromo-1-isopropyl-3-(1-methylindolin-6-yl)-1H-pyrrolo[2,3-b]pyridine수율 68.2%

시약·촉매·용매 4

HCID 178418476HCID 178418476, 화합물촉매HCID 6228Dimethylformamide용매HCID 6342Acetonitrile용매HCID 6344Dichloromethane용매2회

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온도
55 °C

실험 절차

To a stirred suspension of 4-bromo-3-iodo-1-isopropyl-1H-pyrrolo[2,3-b]pyridine (D10) (2.5 g, 6.85 mmol) and 1-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indoline (2.130 g, 8.22 mmol) in ACN (15 mL), DMF (15.00 mL) and DCM (7.50 mL) was added 2M sodium carbonate aq. solution (34.2 mL, 68.5 mmol). Bis(triphenylphosphine)palladium(II) chloride (0.577 g, 0.822 mmol) was then added to the solution and the resulting mixture was heated at 55° C. for ca. 1 hour. Temperature was raised to 65° C. and heated for another 1 hour. The reaction was allowed to cool to RT and diluted with DCM (70 mL). The organic layer was separated and the aqueous layer was extracted with DCM (2×50 mL). The combined organics were dried and concentrated down. The residue obtained was purified on silica using 0-10% ethyl acetate/cyclohexane to afford the title compound (1.73 g). LCMS (A): m/z (M+H)+ 370/372, C19H20BrN3 requires 369/371 (acidic).

후처리

  1. temperatureTemperature was raised to 65° C.
  2. temperatureheated for another 1 hour
  3. temperatureto cool to RT
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with DCM (2×50 mL)
  6. customThe combined organics were dried
  7. concentrationconcentrated down
  8. customThe residue obtained
  9. customwas purified on silica using 0-10% ethyl acetate/cyclohexane

출처 및 근거

ORD 기록
ord-7e274f34a4b24296b445c4a88b963b77
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08877742B2

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