Sodium Chloride → tert-Butyl 4-chloro-3-cyano-5,8-dihydrothieno[2,3-b:5,4-c']dipyridine-7(6H)-carboxylate

HRID 38540Notes

Reaction equation

HRID 38540 reaction equation
S1(CCCC1)(=O)=O.P(Cl)(Cl)(Cl)=O.[C:13]([C:15]1[C:16](O)=[C:17]2[C:27]3[CH2:26][CH2:25][N:24]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:23][C:22]=3[S:21][C:18]2=[N:19][CH:20]=1)#[N:14].[Cl-:36].[Na+]>C(N(CC)CC)C>[Cl:36][C:16]1[C:15]([C:13]#[N:14])=[CH:20][N:19]=[C:18]2[S:21][C:22]3[CH2:23][N:24]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:25][CH2:26][C:27]=3[C:17]=12

Participants

6

Reactant 4

HCID 5234Sodium ChlorideHCID 24813Phosphorus oxychlorideHCID 31347SulfolaneHCID 178451645HCID 178451645, compound

Product 1

HCID 58116935tert-Butyl 4-chloro-3-cyano-5,8-dihydrothieno[2,3-b:5,4-c']dipyridine-7(6H)-carboxylateYield 51%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent2×

Conditions

Temperature
70 °C

Procedure

To sulfolane (10 mL) was added phosphoryl chloride (1.39 g, 9.05 mmol) at rt. Triethylamine (0.92 g, 9.05 mmol) was added dropwise with cooling. tert-Butyl 3-cyano-4-hydroxy-5,8-dihydrothieno[2,3-b:5,4-c′]dipyridine-7(6H)-carboxylate from Example 52A (1.00 g, 3.02 mol) was added, and the mixture was heated to 70° C. for 1.5 h. The mixture was cooled to rt, and triethylamine (2.3 mL) was added. A semi-saturated aqueous sodium chloride solution (10 L) was added whilst cooling with an ice-bath. The mixture was stirred at rt for 30 min and then extracted with ethyl acetate. The organic layer was washed with water, dried over sodium sulfate, and the solvent was removed in vacuo. Toluene was added, and the mixture was washed with water. The organic layer was again dried over sodium sulfate, and the solvent was removed in vacuo. After crystallization, the product was triturated with water, collected by suction filtration and dried to yield 543 mg (51%) of the title compound.

Workup

  1. temperaturewith cooling
  2. temperatureThe mixture was cooled to rt
  3. temperaturewhilst cooling with an ice-bath
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with water
  6. dry with materialdried over sodium sulfate
  7. customthe solvent was removed in vacuo
  8. additionToluene was added
  9. washthe mixture was washed with water
  10. dry with materialThe organic layer was again dried over sodium sulfate
  11. customthe solvent was removed in vacuo
  12. customAfter crystallization
  13. customthe product was triturated with water
  14. filtrationcollected by suction filtration
  15. customdried

Sources & evidence

ORD record
ord-3209f0300e614405afe2972d47a0db72
Source dataset
uspto-grants-2013_09
Patent number
US08524722B2

Reaction notes

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