7-Chlorothieno[3,2-b]pyridine → HCID 66599084, compound

HRID 1475578Notes

Reaction equation

HRID 1475578 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6]N=[C:4]2[CH:8]=[CH:9][S:10][C:3]=12.[Li][CH2:12]CCC.C(OC(=O)[N:22]([CH2:27][C:28]1[CH:29]=[N:30][C:31](Br)=[CH:32][CH:33]=1)[CH2:23][CH2:24][O:25][CH3:26])(C)(C)C>C1COCC1.[Cl-].[Cl-].[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[C:3]2[S:10][C:9]([C:31]3[N:30]=[CH:29][C:28]([CH2:27][NH:22][CH2:23][CH2:24][O:25][CH3:26])=[CH:33][CH:32]=3)=[CH:8][C:4]=2[CH:12]=[CH:6][CH:7]=1

Participants

7

Reactant 3

HCID 112752517-Chlorothieno[3,2-b]pyridineHCID 57919609tert-Butyl [(6-Bromopyridin-3-yl)methyl](2-methoxyethyl)carbamateHCID 178418339Butyllithium

Product 1

HCID 66599084HCID 66599084, compoundYield 83.1%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 7-chlorothieno[3,2-b]pyridine 6 (7.37 g, 43.4 mmol, 1.5 eq) in THF (70 mL) at −10° C. in a 250 mL round-bottom flask was added n-BuLi (17.38 mL, 43.4 mmol, 1.5 eq). After 1 h, ZnCl2 (1M in ether) (43.4 mL, 43.4 mmol, 1.5 eq) was added at −10° C. and the reaction mixture was allowed to warm up to r.t. After 1 h, Pd(PPh3)4 (0.669 g, 0.579 mmol, 0.02 eq) and bromide 10 (10 g, 29 mmol, 1 eq) in THF (10.5 mL) were added and the mixture was heated to reflux for 1 h. After cooling to room temperature the reaction mixture was concentrated to dryness. DCM (200 mL)/water (160 mL)/NH4OH (40 mL) were added to the solid and the resultant mixture (an emulsion) was stirred for 1 h. Brine (50 ml) was added to the emulsion and the stirring was continued for an additional 10 min. The mixture was then filtered through a paper filter and phases were separated. The aqueous phase was extracted with DCM (2×50 mL). The organic phases were combined, dried over Na2SO4 and concentrated to dryness. MTBE (30 mL) was added to the solid and the suspension was stirred for 30 min. The solid was collected by filtration, washed with MTBE (2×5 mL) and dried to afford of 11 as a beige solid (8.02 g, 64% yield). MS (m/z): 434.2 (M+1).

Workup

  1. waitAfter 1 h
  2. temperaturethe mixture was heated
  3. temperatureto reflux for 1 h
  4. temperatureAfter cooling to room temperature the reaction mixture
  5. concentrationwas concentrated to dryness
  6. additionDCM (200 mL)/water (160 mL)/NH4OH (40 mL) were added to the solid
  7. additionBrine (50 ml) was added to the emulsion
  8. waitthe stirring was continued for an additional 10 min
  9. filtrationThe mixture was then filtered through a paper
  10. filtrationfilter
  11. customphases were separated
  12. extractionThe aqueous phase was extracted with DCM (2×50 mL)
  13. dry with materialdried over Na2SO4
  14. concentrationconcentrated to dryness
  15. additionMTBE (30 mL) was added to the solid
  16. stirringthe suspension was stirred for 30 min
  17. filtrationThe solid was collected by filtration
  18. washwashed with MTBE (2×5 mL)
  19. customdried

Sources & evidence

ORD record
ord-7ec8cab0652b42a08cff89e1e4614935
Source dataset
uspto-grants-2015_04
Patent number
US09018378B2

Reaction notes

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