Sodium hydride → 5-(3-(Pyridin-2-yl)isoxazol-5-yl)-3-p-tolyl-1,2,4-oxadiazole

HRID 1951929Notes

Reaction equation

HRID 1951929 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[CH:11]=[C:10]([C:12]([O:14]CC)=O)[O:9][N:8]=1.O/[N:18]=[C:19](\[NH2:27])/[C:20]1[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][CH:21]=1.[H-].[Na+]>CN(C)C=O>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[CH:11]=[C:10]([C:12]2[O:14][N:27]=[C:19]([C:20]3[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][CH:21]=3)[N:18]=2)[O:9][N:8]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 54931684-Methylbenzamide oximeHCID 58062833Ethyl 3-(pyridin-2-yl)isoxazole-5-carboxylate

Product 1

HCID 580628225-(3-(Pyridin-2-yl)isoxazol-5-yl)-3-p-tolyl-1,2,4-oxadiazoleYield 93.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of ethyl 3-(pyridin-2-yl)isoxazole-5-carboxylate (13.6 g, 62.5 mmol) and (Z)—N′-hydroxy-4-methylbenzimidamide (9.68 g, 62.5 mmol) in N,N-dimethylformamide (210 mL) cooled in an ice-bath was added 60% sodium hydride (6.25 g, 156 mmol) portion-wise. After the addition, the reaction mixture was warmed to room temperature and stirred for 1 h. The reaction mixture was concentrated, water (500 mL) was added, and the mixture was stirred at room temperature for 30 minutes. The solid was collected vacuum filtration, triturated with methanol, and re-collected to give 5-(3-(pyridin-2-yl)isoxazol-5-yl)-3-p-tolyl-1,2,4-oxadiazole (17.8 g, 93% yield) as a solid. The compound had an HPLC retention time=3.86 minutes (YMC-Combi 4.6×50 mm S-5 ODS column) eluting with 10-90% aqueous methanol+0.2% phosphoric acid over a 4 minute gradient. MS: (M+H)=305+. 1H NMR (400 MHz, CDCl3) δ ppm 2.46 (s, 3H), 7.35 (d, J=8.28 Hz, 2H), 7.41-7.47 (m, 1H), 7.83-7.91 (m, 2H), 8.09 (d, J=8.28 Hz, 2H), 8.20 (d, J=8.03 Hz, 1H), and 8.76 (d, J=5.02 Hz, 1H).

Workup

  1. additionAfter the addition
  2. concentrationThe reaction mixture was concentrated
  3. additionwater (500 mL) was added
  4. stirringthe mixture was stirred at room temperature for 30 minutes
  5. customThe solid was collected
  6. filtrationvacuum filtration
  7. customtriturated with methanol
  8. customre-collected

Sources & evidence

ORD record
ord-a9641dde8ae446b79f410c1210ba6cfb
Source dataset
uspto-grants-2013_03
Patent number
US08404672B2

Reaction notes

Loading…