Chloroacetyl chloride → 2-chloro-5-(5-(chloromethyl)-1,3,4-oxadiazol-2-yl)-N-isopropylpyridin-4-amine

HRID 595429

Reaction equation

HRID 595429 reaction equation
[Cl:1][C:2]1[CH:11]=[C:10]([NH:12][CH:13]([CH3:15])[CH3:14])[C:5]([C:6]([NH:8][NH2:9])=[O:7])=[CH:4][N:3]=1.CCN(CC)CC.[Cl:23][CH2:24][C:25](Cl)=O.S(Cl)(C1C=CC(C)=CC=1)(=O)=O>C(Cl)Cl>[Cl:1][C:2]1[CH:11]=[C:10]([NH:12][CH:13]([CH3:15])[CH3:14])[C:5]([C:6]2[O:7][C:25]([CH2:24][Cl:23])=[N:9][N:8]=2)=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 6577Chloroacetyl chlorideHCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 896896686-Chloro-4-(isopropylamino)nicotinohydrazide

Product 1

HCID 896908932-chloro-5-(5-(chloromethyl)-1,3,4-oxadiazol-2-yl)-N-isopropylpyridin-4-amine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of 6-chloro-4-(isopropylamino)nicotinohydrazide (10) (500 mg, 2 mmol) in DCM (10 mL), Et3N (6 mmol, 3 equiv.) and 2-chloroacetyl chloride (3 mmol, 1.5 equiv.) were added and stirred at room temperature for 4 h. Added tosyl chloride (3.2 mmol, 1.5 equiv.) was added at stirred overnight at room temperature. The reaction mixture was diluted with DCM. The DCM layer was washed with 10% NaHCO3 solution followed by water. The organic layer was collected, dried over Na2SO4, filtered and concentrated. The crude material obtained was purified by column chromatography through silica gel and EtOAc: Pet. ether as eluent to afford the desired compound, 2-chloro-5-(5-(chloromethyl)-1,3,4-oxadiazol-2-yl)-N-isopropylpyridin-4-amine LC/MS: Acquity BEH C18 2.1×50 mm, 1.8 micron; Solvent A=0.1% TFA in water; Solvent B=0.1% TFA in ACN; gradient 0-100% B over 2 min; retention time: 0.95 min; LCMS (ES-API), m/z 287.6 (M+H).

Workup

  1. stirringat stirred overnight at room temperature
  2. washThe DCM layer was washed with 10% NaHCO3 solution
  3. customThe organic layer was collected
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material obtained
  8. customwas purified by column chromatography through silica gel and EtOAc

Sources & evidence

ORD record
ord-bd99833da3da4504b46c65da299269e8
Source dataset
uspto-grants-2016_01
Patent number
US09242975B2

Linked notes

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