tert-Butyl 4-[({5-[(2-fluorophenyl)amino]-1,3,4-oxadiazol-2-yl}carbonyl)amino]piperidine-1-carboxylate → 5-[(2-fluorophenyl)amino]-N-piperidin-4-yl-1,3,4-oxadiazole-2-carboxamide

HRID 1713876Notes

Reaction equation

HRID 1713876 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9]1[O:13][C:12]([C:14]([NH:16][CH:17]2[CH2:22][CH2:21][N:20](C(OC(C)(C)C)=O)[CH2:19][CH2:18]2)=[O:15])=[N:11][N:10]=1>Cl.O1CCOCC1>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9]1[O:13][C:12]([C:14]([NH:16][CH:17]2[CH2:18][CH2:19][NH:20][CH2:21][CH2:22]2)=[O:15])=[N:11][N:10]=1

Participants

4

Reactant 1

HCID 59464243tert-Butyl 4-[({5-[(2-fluorophenyl)amino]-1,3,4-oxadiazol-2-yl}carbonyl)amino]piperidine-1-carboxylate

Product 1

HCID 594641305-[(2-fluorophenyl)amino]-N-piperidin-4-yl-1,3,4-oxadiazole-2-carboxamideYield 66%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 312751,4-DioxaneSolvent

Procedure

tert-Butyl 4-[({5-[(2-fluorophenyl)amino]-1,3,4-oxadiazol-2-yl}carbonyl)amino]piperidine-1-carboxylate (5.66 g, 13.96 mmol) was suspended in 4M HCl in 1,4-dioxane (50 ml) and stirred for 18 hours. After removal of the solvent in vacuo the residue was partitioned between MeOH:DCM (1:9) (500 mL) and 2M aqueous potassium carbonate (500 mL). The aqueous was extracted with MeOH:DCM (1:9) (7×50 mL) and the combined organics dried (Na2SO4), filtered and concentrated in vacuo. The solid was triturated with hot Et2O (20 mL), filtered then washed with Et2O (20 mL), hexane (20 mL) to leave the title product (Intermediate 101, 2.80 g, 66%) as a beige powder; 1H NMR δ1.44-1.57 (2H, m), 1.66-1.74 (2H, m), 2.47-2.59 (2H, m), 2.94-3.02 (2H, m), 3.74-3.86 (1H, m), 7.04-7.11 (1H, m), 7.17-7.28 (2H, m), 7.96-8.04 (1H, m), 8.92 (1H, d); MS m/e (MH)+ 306.

Workup

  1. customAfter removal of the solvent in vacuo the residue
  2. customwas partitioned between MeOH:DCM (1:9) (500 mL) and 2M aqueous potassium carbonate (500 mL)
  3. extractionThe aqueous was extracted with MeOH:DCM (1:9) (7×50 mL)
  4. dry with materialthe combined organics dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe solid was triturated with hot Et2O (20 mL)
  8. filtrationfiltered
  9. washthen washed with Et2O (20 mL), hexane (20 mL)

Sources & evidence

ORD record
ord-5beb54b9c9f94eea9061a8aeba1e1329
Source dataset
uspto-grants-2010_09
Patent number
US07795283B2

Reaction notes

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