Potassium tert-butoxide → 4-(5-{2-[3-(3-Chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-propyl}-4-cyclopropyl-4H-[1,2,4]triazol-3-yl)-pyridine

HRID 732137Notes

Reaction equation

HRID 732137 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][CH:11]=1)[C:5]([NH:7][OH:8])=[NH:6].CC(C)([O-])C.[K+].C(O[C:21](=O)[CH:22]([CH3:38])[CH2:23][C:24]1[N:28]([CH:29]2[CH2:31][CH2:30]2)[C:27]([C:32]2[CH:37]=[CH:36][N:35]=[CH:34][CH:33]=2)=[N:26][N:25]=1)C>C(O)CC>[Cl:1][C:2]1[CH:3]=[C:4]([C:5]2[N:6]=[C:21]([CH:22]([CH3:38])[CH2:23][C:24]3[N:28]([CH:29]4[CH2:31][CH2:30]4)[C:27]([C:32]4[CH:33]=[CH:34][N:35]=[CH:36][CH:37]=4)=[N:26][N:25]=3)[O:8][N:7]=2)[CH:9]=[CH:10][CH:11]=1

Participants

5

Reactant 3

HCID 23665647Potassium tert-butoxideHCID 578380023-(4-Cyclopropyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-yl)-2-methyl-propionic acid ethyl esterHCID 178513296HCID 178513296, compound

Product 1

HCID 670706264-(5-{2-[3-(3-Chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-propyl}-4-cyclopropyl-4H-[1,2,4]triazol-3-yl)-pyridineYield 59%

Reagents, catalysts & solvents 1

HCID 10311-PropanolSolvent

Conditions

Temperature
100 °C

Procedure

After 3-chloro-N-hydroxy-benzamidine (0.7 g, 4.1 mmol) was mixed with potassium-tert-butoxide (0.373 g, 3.33 mmol) in n-propanol at 80° C. for 10 min, 3-(4-cyclopropyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-yl)-2-methyl-propionic acid ethyl ester (1.0 g, 3.33 mmol) was added to the reaction mixture and heated at 100° C. for 3 h. The reaction mixture was concentrated, quenched with sat. ammonium chloride and extracted with DCM. The organic layer was dried with MgSO4, purified by column chromatography and triturated with Et2O to give racemic 4-(5-{2-[3-(3-chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-propyl}-4-cyclopropyl-4H-[1,2,4]triazol-3-yl)-pyridine (0.8g, 59%). The title product (10 mg) was obtained by separation on Chiracel OJ with EtOH:hex. (1:4). 1H-NMR: 8.78(d, 2H), 8.05 (s, 1H), 7.96 (d, 1H), 7.74 (d, 2H), 7.50 (d, 1H), 7.43 (t, 1H), 4.15 (m, 1H), 3.64 (dd, 1H), 3.31 (m, 2H), 1.67 (d, 3H), 1.25 (m, 2H) and 0.78 (m, 2H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customquenched with sat. ammonium chloride
  3. extractionextracted with DCM
  4. dry with materialThe organic layer was dried with MgSO4
  5. custompurified by column chromatography
  6. customtriturated with Et2O

Sources & evidence

ORD record
ord-3c249d10a2974d2c96a037e64d098d75
Source dataset
uspto-grants-2009_09
Patent number
US07585881B2

Reaction notes

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