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 1400906Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1400906
[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

Komponenten

7

Edukt 3

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

Produkt 1

HCID 584746401-(2-(6-(7-Chlorothieno[3,2-b]pyridin-2-yl)pyridin-3-yl)ethyl)pyrrolidin-2-oneAusbeute 72,3 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 3007855ZincchlorideKatalysatorHCID 11979704Tetrakis(triphenylphosphine)palladiumKatalysatorHCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

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

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-88d7e8e25aa3475183b5052b792d170e
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08906852B2

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