Sodium hydride → 3-[5-(2-Fluoro-phenyl)-pyridin-2-yloxy]-azetidine-1-carboxylic acid (6-methyl-pyridazin-3-yl)-amide

HRID 1469384Notes

Reaction equation

HRID 1469384 reaction equation
[CH3:1][C:2]1[N:7]=[N:6][C:5]([NH2:8])=[CH:4][CH:3]=1.[H-].[Na+].[N+](C1C=CC([O:20][C:21]([N:23]2[CH2:26][CH:25]([O:27][C:28]3[CH:33]=[CH:32][C:31]([C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=4[F:40])=[CH:30][N:29]=3)[CH2:24]2)=O)=CC=1)([O-])=O>CN(C=O)C>[CH3:1][C:2]1[N:7]=[N:6][C:5]([NH:8][C:21]([N:23]2[CH2:24][CH:25]([O:27][C:28]3[CH:33]=[CH:32][C:31]([C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=4[F:40])=[CH:30][N:29]=3)[CH2:26]2)=[O:20])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 877126-Methylpyridazin-3-amineHCID 580731093-[5-(2-Fluoro-phenyl)-pyridin-2-yloxy]-azetidine-1-carboxylic acid 4-nitro-phenyl ester

Product 1

HCID 442190583-[5-(2-Fluoro-phenyl)-pyridin-2-yloxy]-azetidine-1-carboxylic acid (6-methyl-pyridazin-3-yl)-amideYield 49%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 6-Methyl-pyridazin-3-ylamine (60 mg, 0.55 mmol, [Cas. No 18591-82-7]) 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 flash chromatography (40% ethyl acetate in DCM) to give the title compound (48 mg, 49%)

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 flash chromatography (40% ethyl acetate in DCM)

Sources & evidence

ORD record
ord-4828347ea087415cad51efc068f1d623
Source dataset
uspto-grants-2015_04
Patent number
US09006269B2

Reaction notes

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