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 1400906Notes

Reaction equation

HRID 1400906 reaction equation
[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

Participants

7

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

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

Workup

  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

Sources & evidence

ORD record
ord-88d7e8e25aa3475183b5052b792d170e
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

Loading…