Pyridine → N-(6-{[({[3-(dimethylamino)phenyl](1-methyl-1H-tetrazol-5-yl)methylene}amino)oxy]methyl}pyridin-2-yl)-2,2-difluoro-2-phenoxyacetamide

HRID 452566Notes

Reaction equation

HRID 452566 reaction equation
[CH3:1][N:2]([CH3:26])[C:3]1[CH:4]=[C:5]([C:9](=[N:16][O:17][CH2:18][C:19]2[N:24]=[C:23]([NH2:25])[CH:22]=[CH:21][CH:20]=2)[C:10]2[N:14]([CH3:15])[N:13]=[N:12][N:11]=2)[CH:6]=[CH:7][CH:8]=1.N1C=CC=CC=1.[F:33][C:34]([F:45])([O:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[C:35](Cl)=[O:36].C([O-])(O)=O.[Na+]>O1CCOCC1>[CH3:1][N:2]([CH3:26])[C:3]1[CH:4]=[C:5]([C:9](=[N:16][O:17][CH2:18][C:19]2[N:24]=[C:23]([NH:25][C:35](=[O:36])[C:34]([F:33])([F:45])[O:38][C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[CH:22]=[CH:21][CH:20]=2)[C:10]2[N:14]([CH3:15])[N:13]=[N:12][N:11]=2)[CH:6]=[CH:7][CH:8]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 516892Sodium BicarbonateHCID 866531516-{[({[3-(dimethylamino)phenyl](1-methyl-1H-tetrazol-5-yl)methylene}amino)oxy]methyl}pyridin-2-amineHCID 866564042,2-Difluoro-2-phenoxyacetyl chloride

Product 1

HCID 86656403N-(6-{[({[3-(dimethylamino)phenyl](1-methyl-1H-tetrazol-5-yl)methylene}amino)oxy]methyl}pyridin-2-yl)-2,2-difluoro-2-phenoxyacetamideYield 88%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a stirred solution of 6-{[({[3-(dimethylamino)phenyl](1-methyl-1H-tetrazol-5-yl)methylene}amino)oxy]methyl}pyridin-2-amine (90 mg, 0.26 mmol) in dry 1,4-dioxane (10 mL) were added pyridine (31 μL, 0.38 mmol) and 2,2-difluoro-2-phenoxyacetyl chloride (105 mg, 0.51 mmol). The reaction mixture was stirred at room temperature for 25 h, then poured into aq. NaHCO3 (10 g/L, 30 mL). After extraction with ethyl acetate (50 mL), the organic layer was dried (MgSO4) and concentrated in vacuo. Purification on silica gel afforded N-(6-{[({[3-(dimethylamino)phenyl](1-methyl-1H-tetrazol-5-yl)methylene}amino)oxy]methyl}pyridin-2-yl)-2,2-difluoro-2-phenoxyacetamide as an oil [123 mg, yield 88%; HPLC/MS:m/z=523 (M+H); log P(HCOOH)=4.14].

Workup

  1. extractionAfter extraction with ethyl acetate (50 mL)
  2. dry with materialthe organic layer was dried (MgSO4)
  3. concentrationconcentrated in vacuo
  4. customPurification on silica gel

Sources & evidence

ORD record
ord-57f5d1f4ef4f46cea0ad6adca34f77e9
Source dataset
uspto-grants-2013_07
Patent number
US08492388B2

Reaction notes

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