7-Chlorothieno[3,2-b]pyridine → tert-Butyl ((6-(7-chlorothieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methyl)(2-methoxyethyl)carbamate

HRID 84387Notes

Reaction equation

HRID 84387 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.C([Li])CCC.[C:16]([O:20][C:21](=[O:35])[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])([CH3:19])([CH3:18])[CH3:17]>C1COCC1.[Cl-].[Zn+2].[Cl-]>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:31]3[N:30]=[CH:29][C:28]([CH2:27][N:22]([CH2:23][CH2:24][O:25][CH3:26])[C:21](=[O:35])[O:20][C:16]([CH3:17])([CH3:18])[CH3:19])=[CH:33][CH:32]=3)[S:10][C:3]=12

Participants

6

Reactant 3

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

Product 1

HCID 57919613tert-Butyl ((6-(7-chlorothieno[3,2-b]pyridin-2-yl)pyridin-3-yl)methyl)(2-methoxyethyl)carbamateYield 72%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 7-chlorothieno[3,2-b]pyridine (1) (8.84 g, 52.1 mmol) in THF (100 mL) at −78° C. was added n-butyllithium (20.86 mL, 52.1 mmol). After 30 min, zinc chloride (52.1 mL, 52.1 mmol) (1M in ether) was added at −78° C. and the reaction mixture was warmed to r.t. After 1 h, palladium tetrakistriphenylphosphine (1.004 g, 0.869 mmol) and 144 (6 g, 17.38 mmol) in THF (25 mL) were added and the mixture was heated to reflux for 1 h. It was then partitioned between saturated aqueous NaHCO3 solution and EtOAc. The organic layer was collected and the aqueous layer was extracted with EtOAc (3×100 mL). The combined organic layers were washed with brine and evaporated under reduce pressure. The residue was purified by flash column chromatography, eluents Hexane/EtOAc:5/5, 3/7, 0/10, to afford compound 145 (5.41 g, 72% yield). 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.65 (d, J=5.1 Hz, 1H), 8.52 (d, J=1.6 Hz, 1H), 8.39 (s, 1H), 8.27 (d, J=8.0 Hz, 1H), 7.80 (dd, J=8.1, 2.1 Hz, 1H), 7.58 (d, J=5.1 Hz, 1H), 4.48 (s, 2H), 3.43-3.35 (m, 4H), 3.22 (s, 3H), 1.43-1.33 (m, 9H). MS (m/z): 434.2 (M+H).

Workup

  1. waitAfter 1 h
  2. temperaturethe mixture was heated
  3. temperatureto reflux for 1 h
  4. customIt was then partitioned between saturated aqueous NaHCO3 solution and EtOAc
  5. customThe organic layer was collected
  6. extractionthe aqueous layer was extracted with EtOAc (3×100 mL)
  7. washThe combined organic layers were washed with brine
  8. customevaporated
  9. customThe residue was purified by flash column chromatography, eluents Hexane/EtOAc

Sources & evidence

ORD record
ord-d946c4673bae4da790f70afa183bc885
Source dataset
uspto-grants-2014_09
Patent number
US08846927B2

Reaction notes

Loading…