Potassium Carbonate → 4-Chloro-2-{6-oxo-8-thia-4,5-diazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3-trien-5-yl}pyridine-3-carbaldehyde

HRID 592613Notes

Reaction equation

HRID 592613 reaction equation
Br[C:2]1[N:9]=[CH:8][CH:7]=[C:6]([Cl:10])[C:3]=1[CH:4]=[O:5].[C:11]12[CH2:23][CH2:22][CH2:21][CH2:20][C:19]=1[S:18][C:17]1[C:16](=[O:24])[NH:15][N:14]=[CH:13][C:12]2=1.C([O-])([O-])=O.[K+].[K+].COC1C2C(=C3C(=CC=2)C(OC)=CC=N3)N=CC=1>O1CCOCC1.[Cu]I>[Cl:10][C:6]1[CH:7]=[CH:8][N:9]=[C:2]([N:15]2[C:16](=[O:24])[C:17]3[S:18][C:19]4[CH2:20][CH2:21][CH2:22][CH2:23][C:11]=4[C:12]=3[CH:13]=[N:14]2)[C:3]=1[CH:4]=[O:5]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 104622984,7-Dimethoxy-1,10-phenanthrolineHCID 670165536,7,8,9-Tetrahydrobenzo[4,5]thieno[2,3-d]pyridazin-4(3H)-oneHCID 866839142-Bromo-4-chloropyridine-3-carbaldehyde

Product 1

HCID 866842204-Chloro-2-{6-oxo-8-thia-4,5-diazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3-trien-5-yl}pyridine-3-carbaldehydeYield 34.3%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a suspension of 2-bromo-4-chloronicotinaldehyde 103a (641 mg, 2.9 mmol) and 8-thia-4,5-diazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3-trien-6-one 191d (400 mg, 1.94 mmol) in dioxane (20 mL) was added K2CO3 (536 mg, 3.88 mmol), CuI (369 mg, 1.94 mmol), and 4,7-dimethoxy-1,10-phenanthroline (471 mg, 1.96 mmol). After bubbling nitrogen through the resulting solution for 30 min, the mixture was stirred at 80° C. for 16 h. It was allowed to cool to room temperature and added into H2O (100 mL). The aqueous layer was separated and extracted with ethyl acetate (2×200 mL). The combined organic layer was washed with brine (100 mL) and dried over sodium sulfate. The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified on flash column eluting with PE:EA (5:1) to afford 124a (230 mg, 34%). LCMS: [M+H]+ 346

Workup

  1. customAfter bubbling nitrogen through the resulting solution for 30 min
  2. temperatureto cool to room temperature
  3. additionadded into H2O (100 mL)
  4. customThe aqueous layer was separated
  5. extractionextracted with ethyl acetate (2×200 mL)
  6. washThe combined organic layer was washed with brine (100 mL)
  7. dry with materialdried over sodium sulfate
  8. customThe drying agent was removed by filtration
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. customThe residue was purified on flash column
  11. washeluting with PE

Sources & evidence

ORD record
ord-42657523426245778af7c84304d61685
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

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