7-Chlorothieno[3,2-b]pyridine → 6-(7-Chlorothieno[3,2-b]pyridin-2-yl)nicotinaldehyde

HRID 84379Notes

Reaction equation

HRID 84379 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[CH:9][S:10][C:3]=12.[Li]CCCC.Br[C:17]1[N:22]=[CH:21][C:20]([CH:23]=[O:24])=[CH:19][CH:18]=1>C1COCC1.[Cl-].[Zn+2].[Cl-]>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:17]3[CH:18]=[CH:19][C:20]([CH:23]=[O:24])=[CH:21][N:22]=3)[S:10][C:3]=12

Participants

6

Reactant 3

HCID 112752517-Chlorothieno[3,2-b]pyridineHCID 117692346-Bromo-3-pyridinecarboxaldehydeHCID 178418339Butyllithium

Product 1

HCID 579196526-(7-Chlorothieno[3,2-b]pyridin-2-yl)nicotinaldehydeYield 76%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 7-chlorothieno[3,2-b]pyridine (1) (4.02 g, 23.70 mmol) in THF (150 mL) [Klemm, L. H.; Louris, J. N.; Boisvert, W.; Higgins, C.; Muchiri, D. R.; J. Heterocyclic Chem., 22, 1985, 1249-1252] was cooled to −40° C. in an acetonitrile/dry ice bath. n-BuLi (9.95 mL, 24.88 mmol, 2.5M in hexanes) was added by syringe, dropwise. The dark mixture was stirred for 15 min. Zinc chloride (24.88 mL, 24.88 mmol, 1M in ether) was added by syringe. The mixture was warmed to 0° C. then tetrakistriphenylphosphine palladium (1.095 g, 0.948 mmol) was added. The dark mixture was stirred for 10 min and 6-bromopyridine-3-carbaldehyde (4.41 g, 23.70 mmol) was added. The mixture was heated to reflux and a precipitate formed rapidly. After 3 h, the reaction mixture was cooled down to r.t., quenched with 2 mL NH4Cl and left overnight. The solid was isolated by suction filtration, rinsed with small amount of THF and suspended in a mixture of water (200 mL) and EtOAc (100 mL), isolated by suction filtration and finally triturated with acetic acid (100 mL) and dried in vacuum to afford title compound 136 (4.95 g, 76% yield). 1H NMR (400 MHz, DMSO-d6) δ (ppm): 10.13 (s, 1H), 9.14 (d, J=1.4 Hz, 1H), 8.70 (d, J=5.1 Hz, 1H), 8.65 (s, 1H), 8.53 (d, J=8.4 Hz, 1H), 8.39 (dd, J=8.4, 2.1 Hz, 1H), 7.65 (d, J=4.9 Hz, 1H). MS (m/z): 275.1 (M+H).

Workup

  1. stirringThe dark mixture was stirred for 10 min
  2. temperatureThe mixture was heated
  3. temperatureto reflux
  4. customa precipitate formed rapidly
  5. waitAfter 3 h
  6. temperaturethe reaction mixture was cooled down to r.t.
  7. customquenched with 2 mL NH4Cl
  8. waitleft overnight
  9. customThe solid was isolated by suction filtration
  10. washrinsed with small amount of THF
  11. additionsuspended in a mixture of water (200 mL) and EtOAc (100 mL)
  12. customisolated by suction filtration
  13. customfinally triturated with acetic acid (100 mL)
  14. customdried in vacuum

Sources & evidence

ORD record
ord-6367c481cf8b4ec5a1b1411b15b13fd4
Source dataset
uspto-grants-2014_09
Patent number
US08846927B2

Reaction notes

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