Triethylamine → 3-((4-(6-Bromo-1-(methylsulfonyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-1H-pyrazol-1-yl)methyl)-5-methylisoxazole

HRID 2205872노트

반응식

HRID 2205872 반응식
[Br:1][C:2]1[CH:7]=[C:6]([NH:8][S:9]([CH3:12])(=[O:11])=[O:10])[C:5](I)=[CH:4][N:3]=1.[C:14]([C:16]1[CH:17]=[N:18][N:19]([CH2:21][C:22]2[CH:26]=[C:25]([CH3:27])[O:24][N:23]=2)[CH:20]=1)#[CH:15].C(N(CC)CC)C>CN(C=O)C.O.ClCCl.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.[Cu](I)I>[Br:1][C:2]1[N:3]=[CH:4][C:5]2[CH:15]=[C:14]([C:16]3[CH:17]=[N:18][N:19]([CH2:21][C:22]4[CH:26]=[C:25]([CH3:27])[O:24][N:23]=4)[CH:20]=3)[N:8]([S:9]([CH3:12])(=[O:11])=[O:10])[C:6]=2[CH:7]=1

참가 물질

9

반응물 3

HCID 8471TriethylamineHCID 86706267N-(2-Bromo-5-iodopyridin-4-yl)methanesulfonamideHCID 867062833-((4-Ethynyl-1H-pyrazol-1-yl)methyl)-5-methylisoxazole

생성물 1

HCID 867062843-((4-(6-Bromo-1-(methylsulfonyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-1H-pyrazol-1-yl)methyl)-5-methylisoxazole수율 52.1%

시약·촉매·용매 5

HCID 83717Copper iodide촉매HCID 178418476HCID 178418476, 화합물촉매HCID 962Water용매HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

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온도
60 °C

실험 절차

Bis(triphenylphosphine)palladium dichloride (46 mg, 0.066 mmol) was added to a solution of N-(2-bromo-5-iodopyridin-4-yl)methanesulfonamide (8) (0.5 g, 1.32 mmol), 3-((4-ethynyl-1H-pyrazol-1-yl)methyl)-5-methylisoxazole (32) (0.278 g, 1.48 mmol), triethylamine (0.7 g, 7 mmol) and copper iodide (13 mg, 0.065 mmol) in DMF (5 ml). The reaction mixture was heated for 1 h at 60° C. The reaction mixture was cooled to room temperature and diluted with water (20 ml) and dichloromethane (30 ml). The organic solution was dried and concentrated in vacuo. The crude product was purified by flash silica chromatography (10 to 20% ethyl acetate in hexane) to afford the product as a white powder (300 mg, 51.8%). 1H-NMR (500 MHz, CDCl3) 2.43 (s, 3H), 2.96 (s, 3H), 5.41 (s, 2H), 6.02 (s, 1H), 6.69 (s, 1H), 7.78 (s, 1H), 7.87 (s, 1H), 8.22 (s, 1H), 8.62 (s, 1H).

후처리

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customThe organic solution was dried
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified by flash silica chromatography (10 to 20% ethyl acetate in hexane)

출처 및 근거

ORD 기록
ord-3420180069364b38956c6984453ba5c5
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09371319B2

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