7-Chlorothieno[3,2-b]pyridine → 1-(2-(6-(7-Chlorothieno[3,2-b]pyridin-2-yl)pyridin-3-yl)ethyl)pyrrolidin-2-one

HRID 1400906노트

반응식

HRID 1400906 반응식
[Cl:1][C:2]1[C:7]2[S:8][CH:9]=[CH:10][C:6]=2[N:5]=[CH:4][CH:3]=1.C([Li])CCC.Br[C:17]1[N:22]=[CH:21][C:20]([CH2:23][CH2:24][N:25]2[CH2:29][CH2:28][CH2:27][C:26]2=[O:30])=[CH:19][CH:18]=1>C1COCC1.[Cl-].[Zn+2].[Cl-].[Pd].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.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>[Cl:1][C:2]1[CH:3]=[CH:4][N:5]=[C:6]2[CH:10]=[C:9]([C:17]3[N:22]=[CH:21][C:20]([CH2:23][CH2:24][N:25]4[CH2:29][CH2:28][CH2:27][C:26]4=[O:30])=[CH:19][CH:18]=3)[S:8][C:7]=12

참가 물질

7

반응물 3

HCID 112752517-Chlorothieno[3,2-b]pyridineHCID 584748611-(2-(6-Bromopyridin-3-yl)ethyl)pyrrolidin-2-oneHCID 178418339Butyllithium

생성물 1

HCID 584746401-(2-(6-(7-Chlorothieno[3,2-b]pyridin-2-yl)pyridin-3-yl)ethyl)pyrrolidin-2-one수율 72.3%

시약·촉매·용매 3

HCID 3007855Zincchloride촉매HCID 11979704Tetrakis(triphenylphosphine)palladium촉매HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
0 °C

실험 절차

To 7-chlorothienopyridine (0.95 g, 5.6 mmol) in THF (75 mL) at −78° C. was added n-butyllithium (2.5 M in hexanes, 2.4 mL, 6.0 mmol), dropwise. The solution was stirred for 30 min then warmed to 0° C. and zinc chloride (1.0 M in ether, 6.5 mL, 6.5 mmol) was added. The reaction mixture was stirred for 20 min, then bromide 291 (1.25 g, 4.64 mmol) and tetrakis(triphenylphosphine) palladium (0.5.4 g, 0.46 mmol) in THF (15 mL) were added. The mixture then was heated to reflux for 3 h and cooled to RT. The excess base was quenched with 1 mL saturated aqueous ammonium chloride, and the mixture was concentrated. The residue was partitioned between water and diethyl ether, producing a yellow precipitate, which was isolated by suction filtration, triturated with ethyl acetate and dried in vacuo to give title compound 292 (1.2 g, 72%). MS (M+H): 358.3

후처리

  1. stirringThe reaction mixture was stirred for 20 min
  2. temperatureThe mixture then was heated
  3. temperatureto reflux for 3 h
  4. temperaturecooled to RT
  5. customThe excess base was quenched with 1 mL saturated aqueous ammonium chloride
  6. concentrationthe mixture was concentrated
  7. customThe residue was partitioned between water and diethyl ether
  8. customproducing a yellow precipitate
  9. customwhich was isolated by suction filtration
  10. customtriturated with ethyl acetate
  11. customdried in vacuo

출처 및 근거

ORD 기록
ord-88d7e8e25aa3475183b5052b792d170e
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08906852B2

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