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

HRID 330997ノート

反応式

HRID 330997 の反応式
[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

参加物

8

反応物 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

生成物 1

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

試薬・触媒・溶媒 4

HCID 178418476HCID 178418476、化合物触媒HCID 6228Dimethylformamide溶媒HCID 6342Acetonitrile溶媒HCID 6344Dichloromethane溶媒2 回

反応条件

温度
55 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-7e274f34a4b24296b445c4a88b963b77
出典データセット
uspto-grants-2014_11
特許番号
US08877742B2

反応ノート

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