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

HRID 2304878Notes

Reaction equation

HRID 2304878 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 94.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
45 °C

Procedure

4-Hydroxy-5-isobutyryl-3-methyl-2-phenylthieno[2,3-b]pyridine (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 reaction mixture was stirred at 40 to 50° C. for 2 hours. The reaction mixture was treated dropwise with water (560 ml), and the mixture was stirred for 1 hour and then cooled on ice, and then stirred further for 1 hour. The crude crystal was recovered by a filtration, washed with water (about 1000 ml), dried in air, suspended in a 1:1 solvent mixture (250 ml) of ethyl acetate and diisopropylether, and then the mixture was stirred at room temperature for 1 hour, and then stirred with cooling on ice for 1 hour. The crystal obtained by a filtration was washed with the same solvent mixture (180 ml), dried in vacuo at 40° C. for 5 hours to obtain the title compound (46.53 g, 94.6%).

Workup

  1. stirringthe mixture was stirred for 1 hour
  2. temperaturecooled on ice
  3. stirringstirred further for 1 hour
  4. filtrationThe crude crystal was recovered by a filtration
  5. washwashed with water (about 1000 ml)
  6. customdried in air
  7. stirringthe mixture was stirred at room temperature for 1 hour
  8. stirringstirred
  9. temperaturewith cooling on ice for 1 hour
  10. customThe crystal obtained by a filtration
  11. washwas washed with the same solvent mixture (180 ml)
  12. customdried in vacuo at 40° C. for 5 hours

Sources & evidence

ORD record
ord-b5b553cccbd54cc9a7e317cf96dfd2c5
Source dataset
uspto-grants-2002_08
Patent number
US06437132B2

Reaction notes

Loading…