Sodium hydride → 3-[5-(2-Fluoro-phenyl)-pyridin-2-yloxy]-azetidine-1-carboxylic acid (5-methyl-[1,3,4]oxadiazol-2-yl)-amide

HRID 1469386Notes

Reaction equation

HRID 1469386 reaction equation
[CH3:1][C:2]1[O:6][C:5]([NH2:7])=[N:4][N:3]=1.[H-].[Na+].[N+](C1C=CC([O:19][C:20]([N:22]2[CH2:25][CH:24]([O:26][C:27]3[CH:32]=[CH:31][C:30]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=4[F:39])=[CH:29][N:28]=3)[CH2:23]2)=O)=CC=1)([O-])=O>CN(C=O)C>[CH3:1][C:2]1[O:6][C:5]([NH:7][C:20]([N:22]2[CH2:23][CH:24]([O:26][C:27]3[CH:32]=[CH:31][C:30]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=4[F:39])=[CH:29][N:28]=3)[CH2:25]2)=[O:19])=[N:4][N:3]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 20602505-Methyl-1,3,4-oxadiazol-2-amineHCID 580731093-[5-(2-Fluoro-phenyl)-pyridin-2-yloxy]-azetidine-1-carboxylic acid 4-nitro-phenyl ester

Product 1

HCID 442192133-[5-(2-Fluoro-phenyl)-pyridin-2-yloxy]-azetidine-1-carboxylic acid (5-methyl-[1,3,4]oxadiazol-2-yl)-amideYield 11%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 5-Methyl-[1,3,4]oxadiazol-2-ylamine (31 mg, 0.31 mmol, [Cas. No. 52838-39-8]) in DMF (3 mL) at 0° C. was added sodium hydride (20 mg, 0.5 mmol, 60% disp. in mineral oil). After stirring at 0° C. for 15 min. a solution of 3-[5-(2-Fluoro-phenyl)-pyridin-2-yloxy]-azetidine-1-carboxylic acid 4-nitro-phenyl ester (102 mg, 0.25 mmol) in DMF (4 mL) was added dropwise. After stirring for 16 hrs at ambient temperature the reaction mixture was concentrated in vacuo, diluted with ethyl acetate (50 mL) and washed sequentially with sat. aqueous sodium hydrogen carbonate solution (2×50 mL) then sat. sodium chloride solution (50 mL). Mixture dried over magnesium sulphate and filtered. Filtrate solvents were removed in vacuo and the residue was purified by preparative HPLC to give the title compound (10 mg, 11%)

Workup

  1. additionwas added dropwise
  2. concentrationwas concentrated in vacuo
  3. additiondiluted with ethyl acetate (50 mL)
  4. washwashed sequentially with sat. aqueous sodium hydrogen carbonate solution (2×50 mL)
  5. dry with materialMixture dried over magnesium sulphate
  6. filtrationfiltered
  7. customFiltrate solvents were removed in vacuo
  8. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-bbd80c3f96974456b34eab012e07c61f
Source dataset
uspto-grants-2015_04
Patent number
US09006269B2

Reaction notes

Loading…