Water → 2-(3,4-Diethoxyphenyl)-5-(pyridin-4-yl)-1,3,4-oxadiazole

HRID 447897

Reaction equation

HRID 447897 reaction equation
C([O-])([O-])=O.[Na+].[Na+].[N:7]1[CH:12]=[CH:11][C:10]([C:13]([NH:15][NH2:16])=[O:14])=[CH:9][CH:8]=1.[CH2:17]([O:19][C:20]1[CH:21]=[C:22]([CH:26]=[CH:27][C:28]=1[O:29][CH2:30][CH3:31])[C:23](Cl)=O)[CH3:18].O>CN1C(=O)CCC1>[CH2:17]([O:19][C:20]1[CH:21]=[C:22]([C:23]2[O:14][C:13]([C:10]3[CH:11]=[CH:12][N:7]=[CH:8][CH:9]=3)=[N:15][N:16]=2)[CH:26]=[CH:27][C:28]=1[O:29][CH2:30][CH3:31])[CH3:18]

Participants

6

Reactant 4

HCID 962WaterHCID 3767IsoniazidHCID 10340Sodium CarbonateHCID 27582343,4-Diethoxybenzoyl chloride

Product 1

HCID 8564702-(3,4-Diethoxyphenyl)-5-(pyridin-4-yl)-1,3,4-oxadiazoleYield 67%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent2×

Procedure

To a stirred solution of 3,4-diethoxybenzoic acid (0.71 mmol, 150 mg) in CH2Cl2 was added SOCl2 at room temperature; the reaction was refluxed for 1.5 h and the mixture concentrated under reduced pressure to yield 3,4-diethoxybenzoylchloride quantitatively. To a stirred suspension of Na2CO3 (1.42 mmol, 150.52 mg) and pyridine-4-carbohydrazide (0.71 mmol, 97 mg) in NMP (0.8 mL) was added a solution of the 3,4-diethoxybenzoylchloride in NMP (0.8 mL) and the reaction was stirred for 12 h at room temperature. The mixture was poured into 20 mL of cold H2O and filtered. The precipitated intermediate was dried in vacuum. The solid was added to POCl3 (5 mL) and heated to 70-72° C. for 6 h. The solution was poured into an ice-water container and neutralized with a solution of NaOH (2M). The precipitated product was filtered and purified by column chromatography using CH2Cl2:MeOH (9:1) to yield the product as white solid in 67% yield (150 mg). 1H NMR (400 MHz, CDCl3): δ 8.84 (bs, 2H), 7.99 (d, J=4.4 Hz, 2H), 7.67 (dd, J1=2.0, J2=8.4 Hz, 1H), 7.64 (d, J=2.0 Hz, 1H), 6.98 (d, J=8.4 Hz, 1H), 4.20 (q, J=7.2 Hz, 2H), 4.18 (q, J=7.2 Hz, 2H), 1.51 (t, J=7.2 Hz, 3H), 1.50 (t, J=7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ165.81, 162.46, 152.51, 150.84, 149.20, 131.52, 128.05, 120.97, 115.77, 112.78, 111.58, 65.05, 64.80, 14.92, 14.85. MS (EI) m/z: 312 (M+), HRMS (EI) for C17H17N3O3 (M+): calcd 312.1343. found 312.1350.

Workup

  1. filtrationfiltered
  2. customThe precipitated intermediate was dried in vacuum
  3. additionThe solid was added to POCl3 (5 mL)
  4. temperatureheated to 70-72° C. for 6 h
  5. additionThe solution was poured into an ice-water container
  6. filtrationThe precipitated product was filtered
  7. custompurified by column chromatography

Sources & evidence

ORD record
ord-7c9c77156ae049d4b39c06ceaa807a47
Source dataset
uspto-grants-2013_07
Patent number
US08481573B2

Linked notes

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