Hydrazine hydrate (1:1) → 3-(4-cyclopropyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-yl)-2-methyl-propionic acid hydrazide

HRID 732138Notes

Reaction equation

HRID 732138 reaction equation
C([O:3][C:4](=O)[CH:5]([CH3:21])[CH2:6][C:7]1[N:11]([CH:12]2[CH2:14][CH2:13]2)[C:10]([C:15]2[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=2)=[N:9][N:8]=1)C.O.[NH2:24][NH2:25]>C(O)C>[CH:12]1([N:11]2[C:10]([C:15]3[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=3)=[N:9][N:8]=[C:7]2[CH2:6][CH:5]([CH3:21])[C:4]([NH:24][NH2:25])=[O:3])[CH2:14][CH2:13]1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 578380023-(4-Cyclopropyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-yl)-2-methyl-propionic acid ethyl ester

Product 1

HCID 670709833-(4-cyclopropyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-yl)-2-methyl-propionic acid hydrazide

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

3-(4-cyclopropyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-yl)-2-methyl-propionic acid ethyl ester (2.14 g, 7.1 mmol) was mixed with hydrazine monohydrate in ethanol at 120° C. in a sealed flask for 2 hours. The reaction mixture was concentrated and triturated with ether to give 3-(4-cyclopropyl-5-pyridin-4-yl-4H-[1,2,4]triazol-3-yl)-2-methyl-propionic acid hydrazide. This compound was mixed with 3-Chloro-benzimidic acid ethyl ester hydrochloride (0.722 g, 7.8 mmol) in ethanol at 130° C. o.n. The reaction mixture was concentrated, quenched with saturated sodium carbonate, extracted with DCM. The organic layer was dried and purified by column chromatograph with 5% methanol (2M NH3) in DCM to 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 1.19 g (41.1%). This material (70 mg) was separated on Chiralpak AD using ethanol as eluent to give the title compound. 1H-NMR: 8.77(d, 2H), 8.02 (s, 1H), 7.92 (d, 1H), 7.72 (d, 2H), 7.51 (d, 1H), 7.47(t, 1H), 4.12 (m, 1H), 3.69 (dd, 1H), 3.44 (m, 1H), 3.26 (dd, 1H), 1.66 (d, 3H), 1.24 (m, 2H) and 0.79 (m, 2H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customtriturated with ether

Sources & evidence

ORD record
ord-970d7fa4823648049364c5deea8073b8
Source dataset
uspto-grants-2009_09
Patent number
US07585881B2

Reaction notes

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