Water → 8-[(3,4-Dichlorobenzyl)oxy]-8-(3,4-difluorophenyl)-3-[3-methoxy-4-(2-methyl-1,3-oxazol-5-yl)phenyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine

HRID 71101Notes

Reaction equation

HRID 71101 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:9]2[CH2:14][CH2:13][CH2:12][N:11]3[C:15]([C:18]4[CH:23]=[CH:22][C:21]([C:24]5[O:28][C:27]([CH3:29])=[N:26][CH:25]=5)=[C:20]([O:30][CH3:31])[CH:19]=4)=[N:16][N:17]=[C:10]23)[CH:5]=[CH:6][C:7]=1[F:8].[H-].[Na+].Br[CH2:35][C:36]1[CH:41]=[CH:40][C:39]([Cl:42])=[C:38]([Cl:43])[CH:37]=1.[OH2:44]>CN(C=O)C>[Cl:43][C:38]1[CH:37]=[C:36]([CH:41]=[CH:40][C:39]=1[Cl:42])[CH2:35][O:44][C:9]1([C:4]2[CH:5]=[CH:6][C:7]([F:8])=[C:2]([F:1])[CH:3]=2)[CH2:14][CH2:13][CH2:12][N:11]2[C:15]([C:18]3[CH:23]=[CH:22][C:21]([C:24]4[O:28][C:27]([CH3:29])=[N:26][CH:25]=4)=[C:20]([O:30][CH3:31])[CH:19]=3)=[N:16][N:17]=[C:10]12

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydride2×HCID 6397264-(Bromomethyl)-1,2-dichlorobenzeneHCID 666088538-(3,4-Difluorophenyl)-3-[3-methoxy-4-(2-methyl-1,3-oxazol-5-yl)phenyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine

Product 1

HCID 666042238-[(3,4-Dichlorobenzyl)oxy]-8-(3,4-difluorophenyl)-3-[3-methoxy-4-(2-methyl-1,3-oxazol-5-yl)phenyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 8-(3,4-difluorophenyl)-3-[3-methoxy-4-(2-methyl-1,3-oxazol-5-yl)phenyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine (100 mg) in DMF (2 mL) was added sodium hydride (60%, 14.2 mg), and the mixture was stirred at room temperature for 30 min in the air. Sodium hydride (60%, 14.2 mg) was added, and the mixture was further stirred at room temperature for 30 min in the air. 4-(Bromomethyl)-1,2-dichlorobenzene (85.2 mg) was added, and the mixture was stirred at room temperature for 2 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium hydrogen carbonate solution, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane), and further recrystallized from ethyl acetate/hexane to give the title compound (64.8 mg).

Workup

  1. stirringthe mixture was further stirred at room temperature for 30 min in the air
  2. stirringthe mixture was stirred at room temperature for 2 hr
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe extract was washed with saturated aqueous sodium hydrogen carbonate solution
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)
  8. customfurther recrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-0de28bfff32d4ce59c8adde612f52098
Source dataset
uspto-grants-2014_09
Patent number
US08822699B2

Reaction notes

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