Nitrogen → 4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(5-(methylthio)-1H-tetrazol-1-yl)propyl)pyridin-3-yl)oxy)benzonitrile

HRID 63263Notes

Reaction equation

HRID 63263 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([OH:35])([CH2:28][N:29]1[C:33](=[S:34])[NH:32][N:31]=[N:30]1)[C:10]([C:13]1[N:18]=[CH:17][C:16]([O:19][C:20]2[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[CH:22][CH:21]=2)=[CH:15][CH:14]=1)([F:12])[F:11].[H-].[Na+].N#N.[CH3:40]I>C1COCC1>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([OH:35])([CH2:28][N:29]1[C:33]([S:34][CH3:40])=[N:32][N:31]=[N:30]1)[C:10]([C:13]1[N:18]=[CH:17][C:16]([O:19][C:20]2[CH:21]=[CH:22][C:23]([C:24]#[N:25])=[CH:26][CH:27]=2)=[CH:15][CH:14]=1)([F:12])[F:11]

Participants

6

Reactant 4

HCID 947NitrogenHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 178510080HCID 178510080, compound

Product 1

HCID 863429034-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(5-(methylthio)-1H-tetrazol-1-yl)propyl)pyridin-3-yl)oxy)benzonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a magnetically stirred mixture of 4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(5-thioxo-4,5-dihydro-1H-tetrazol-1-yl)propyl)pyridin-3-yl)oxy)benzonitrile (100 mg, 0.199 mmol) in dry THF (1990 μL) was added sodium hydride (17.51 mg, 0.438 mmol) in a 10 mL vial under N2 atmosphere. The reaction mixture was stirred at 0° C. for 15 min at which point methyl iodide (12.44 μL, 0.199 mmol) was added via microsyringe. The reaction was allowed to continue stifling at 0° C. for 1 hour. At this point the reaction was quenched with water and allowed to stir, then removed from the ice bath and extracted with CH2Cl2 (3×). The combined organic layers were dried by passing through a phase separator and volatiles were removed under a gentle stream of N2. The resulting residue was loaded onto a pad of celite and purified (SiO2, 10-35% Ethyl Acetate/Hexanes over 8 min, 35% for 4 min) to give the title compound as an off white foamy solid (82 mg, 76%).

Workup

  1. additionwas added via microsyringe
  2. customAt this point the reaction was quenched with water
  3. customremoved from the ice bath
  4. extractionextracted with CH2Cl2 (3×)
  5. customThe combined organic layers were dried
  6. customwere removed under a gentle stream of N2
  7. custompurified (SiO2, 10-35% Ethyl Acetate/Hexanes over 8 min, 35% for 4 min)

Sources & evidence

ORD record
ord-fffaef98485f4b1dbb6110f57ad7dd7b
Source dataset
uspto-grants-2016_09
Patent number
US09447073B2

Reaction notes

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