Pyridine → Ethyl 3-(3-{5-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]-1,3,4-thiadiazol-2-yl}-1,2,4-oxadiazol-5-yl)propanoate

HRID 561226Notes

Reaction equation

HRID 561226 reaction equation
[Br:1][C:2]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:3]=1[O:4][CH:5]1[CH2:10][CH2:9][N:8]([C:11]2[S:15][C:14]([C:16](=[N:18][OH:19])[NH2:17])=[N:13][N:12]=2)[CH2:7][CH2:6]1.N1C=CC=C[CH:26]=1.Cl[C:32](=O)[CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35]>C(Cl)Cl>[Br:1][C:2]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:3]=1[O:4][CH:5]1[CH2:10][CH2:9][N:8]([C:11]2[S:15][C:14]([C:16]3[N:17]=[C:26]([CH2:32][CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35])[O:19][N:18]=3)=[N:13][N:12]=2)[CH2:7][CH2:6]1

Participants

5

Reactant 3

HCID 1049PyridineHCID 118931Ethyl 3-chloro-3-oxopropionateHCID 1363601515-[4-(2-Bromo-5-fluorophenoxy)piperidin-1-yl]-N'-hydroxy-1,3,4-thiadiazole-2-carboximidamide

Product 1

HCID 66696811Ethyl 3-(3-{5-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]-1,3,4-thiadiazol-2-yl}-1,2,4-oxadiazol-5-yl)propanoate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

5-[4-(2-Bromo-5-fluorophenoxy)piperidin-1-yl]-N′-hydroxy-1,3,4-thiadiazole-2-carboximidamide (500 mg, 1.2 mmol) was dissolved in CH2Cl2 (5 mL) and cooled to 0° C. in an ice-water bath. To this solution was added pyridine (0.155 mL, 1.92 mmol) followed by ethyl 3-chloro-3-oxopropanoate (270 mg, 1.8 mmol). After stirring for 1 h, the solvent was removed in vacuo. The residue was dissolved in pyridine (8 mL) and stirred at 90° C. overnight. The solvent was removed and the residue was partitioned between EtOAc and water. The combined organic layers were dried over anhydrous Na2SO4, filtered and evaporated in vacuo. The crude product was purified by preparative TLC to afford the title compound.

Workup

  1. customthe solvent was removed in vacuo
  2. dissolutionThe residue was dissolved in pyridine (8 mL)
  3. stirringstirred at 90° C. overnight
  4. customThe solvent was removed
  5. customthe residue was partitioned between EtOAc and water
  6. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customThe crude product was purified by preparative TLC

Sources & evidence

ORD record
ord-4d412c7bf99f4a64b50636461e6268ba
Source dataset
uspto-grants-2011_11
Patent number
US08063224B2

Reaction notes

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