4-[3-(Chloromethyl)-1,2,4-oxadiazol-5-yl]pyridine → (R)-3-((R)-2-phenyl-2-(phenylamino)acetoxy)-1-((5-(pyridin-4-yl)-1,2,4-oxadiazol-3-yl)methyl)-1-azoniabicyclo[2.2.2]octane chloride

HRID 1044071Notes

Reaction equation

HRID 1044071 reaction equation
[Cl:1][CH2:2][C:3]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=2)[O:5][N:4]=1.[C:14]1([C@@H:20]([NH:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:21]([O:23][C@@H:24]2[CH:29]3[CH2:30][CH2:31][N:26]([CH2:27][CH2:28]3)[CH2:25]2)=[O:22])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.CC#N.O>CCOC(C)=O>[Cl-:1].[C:14]1([C@@H:20]([NH:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:21]([O:23][C@@H:24]2[CH:29]3[CH2:28][CH2:27][N+:26]([CH2:2][C:3]4[N:7]=[C:6]([C:8]5[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=5)[O:5][N:4]=4)([CH2:31][CH2:30]3)[CH2:25]2)=[O:22])[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

5

Reactant 3

HCID 162285964-[3-(Chloromethyl)-1,2,4-oxadiazol-5-yl]pyridineHCID 18373917Acetonitrile--water (1/1)HCID 46840261(R)-((R)-quinuclidin-3-yl) 2-phenyl-2-(phenylamino)acetate

Product 1

HCID 54766847(R)-3-((R)-2-phenyl-2-(phenylamino)acetoxy)-1-((5-(pyridin-4-yl)-1,2,4-oxadiazol-3-yl)methyl)-1-azoniabicyclo[2.2.2]octane chlorideYield 40.5%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

3-(Chloromethyl)-5-(pyridin-4-yl)-1,2,4-oxadiazole (I51) (45.0 mg, 0.23 mmol) was added to a solution of (R)—((R)-quinuclidin-3-yl) 2-phenyl-2-(phenylamino)acetate (diastereomer 1 of I2) (50 mg, 0.15 mmol) in EtOAc (2 ml). The reaction mixture was heated under microwave irradiation at 80° C. for 3 hours. The solvent was evaporated, and the residue was triturated with Et2O, filtered and dried. The product was purified by flash-chromatography (DCM/MeOH=97/3 to 9/1) and then by preparative HPLC (eluents: CH3CN/H2O) to obtain (R)-3-((R)-2-phenyl-2-(phenylamino)acetoxy)-1-((5-(pyridin-4-yl)-1,2,4-oxadiazol-3-yl)methyl)-1-azoniabicyclo[2.2.2]octane chloride (32.3 mg, 29.0% yield).

Workup

  1. customThe solvent was evaporated
  2. customthe residue was triturated with Et2O
  3. filtrationfiltered
  4. customdried
  5. customThe product was purified by flash-chromatography (DCM/MeOH=97/3 to 9/1)

Sources & evidence

ORD record
ord-e8d7d34b911e40a49a467b122a521a72
Source dataset
uspto-grants-2013_10
Patent number
US08563577B2

Reaction notes

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