Dimethylformamide → 7-(2,6-Difluorobenzyl)-4,7-dihydro-5-isobutyryl-3-methyl-4-oxo-2-phenylthieno[2,3-b]pyridine

HRID 2304874Notes

Reaction equation

HRID 2304874 reaction equation
[OH:1][C:2]1[C:7]([C:8](=[O:12])[CH:9]([CH3:11])[CH3:10])=[CH:6][N:5]=[C:4]2[S:13][C:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[C:15]([CH3:16])[C:3]=12.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O.[F:34][C:35]1[CH:42]=[CH:41][CH:40]=[C:39]([F:43])[C:36]=1[CH2:37]Br>O>[F:34][C:35]1[CH:42]=[CH:41][CH:40]=[C:39]([F:43])[C:36]=1[CH2:37][N:5]1[CH:6]=[C:7]([C:8](=[O:12])[CH:9]([CH3:11])[CH3:10])[C:2](=[O:1])[C:3]2[C:15]([CH3:16])=[C:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[S:13][C:4]1=2

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 5814352-(Bromomethyl)-1,3-difluorobenzeneHCID 178421951HCID 178421951, compound

Product 1

HCID 120498617-(2,6-Difluorobenzyl)-4,7-dihydro-5-isobutyryl-3-methyl-4-oxo-2-phenylthieno[2,3-b]pyridineYield 91.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

The compound obtained in Example 14 (35 g), potassium carbonate (18.6 g) and N,N-dimethylformamide (280 ml) were mixed, and 2,6-difluorobenzyl bromide (27.9 g) was added, and the mixture was stirred at room temperature for 4 hours. Water (560 ml) was added dropwise to the reaction mixture, and the mixture was stirred for 30 minutes,-cooled on ice, and then stirred further for 1 hour. The crude crystal was recovered by a filtration, washed with water, dried in air, and then suspended in a 1:1 solvent mixture (250 ml) of ethyl acetate and diisopropylether, and the suspension was stirred at 25 to 40° C. for 1 hour, and then stirred with cooling on ice for 1 hour, and the crystal precipitated out was recovered by a filtration and washed with the solvent mixture described above (125 ml) to obtain the title compound (44.6 g, 91.7%).

Workup

  1. stirringthe mixture was stirred for 30 minutes
  2. stirringstirred further for 1 hour
  3. filtrationThe crude crystal was recovered by a filtration
  4. washwashed with water
  5. customdried in air
  6. stirringthe suspension was stirred at 25 to 40° C. for 1 hour
  7. stirringstirred
  8. temperaturewith cooling on ice for 1 hour
  9. customthe crystal precipitated out
  10. filtrationwas recovered by a filtration
  11. washwashed with the solvent mixture

Sources & evidence

ORD record
ord-4454907a028a4834ba1950a353b38bdc
Source dataset
uspto-grants-2002_08
Patent number
US06437132B2

Reaction notes

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