Triethylamine → N-(5-tert-butyl-1,3,4-thiadiazol-2-yl)-5-chloro-2-methoxybenzamide

HRID 717220Notes

Reaction equation

HRID 717220 reaction equation
[NH2:1][C:2]1[S:3][C:4]([C:7]([CH3:10])([CH3:9])[CH3:8])=[N:5][N:6]=1.[Cl:11][C:12]1[CH:13]=[CH:14][C:15]([O:21][CH3:22])=[C:16]([CH:20]=1)[C:17](O)=[O:18].C(N(CC)CC)C.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O.C(OCC)(=O)C>O1CCCC1>[C:7]([C:4]1[S:3][C:2]([NH:1][C:17](=[O:18])[C:16]2[CH:20]=[C:12]([Cl:11])[CH:13]=[CH:14][C:15]=2[O:21][CH3:22])=[N:6][N:5]=1)([CH3:10])([CH3:9])[CH3:8]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 769705-Chloro-o-anisic acidHCID 111923Propylphosphonic anhydrideHCID 170170Buthidazolamine

Product 1

HCID 2914804N-(5-tert-butyl-1,3,4-thiadiazol-2-yl)-5-chloro-2-methoxybenzamideYield 87.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-amino-5-tert-butyl-1,3,4-thiadiazole (Aldrich) (2.5 g, 16.3 mmol) in tetrahydrofuran (30 mL) were added 5-chloro-2-methoxybenzoic acid (Aldrich) (3.65 g, 19.6 mmol), triethylamine (5.5 mL, 39.5 mmol), and 1-propanephosphonic acid cyclic anhydride 50% solution in ethyl acetate (Aldrich) (11.6 mL, 19.6 mmol). The reaction mixture was stirred at about room temperature for 14 hours, cooled with external ice bath while quenching with saturated aqueous NaHCO3 (20 mL). The aqueous layer was extracted with ethyl acetate (2×40 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography using an Analogix® Intelliflash280™ (SiO2, 0-100% ethyl acetate in hexanes) to afford 4.65 g of the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.43 (s, 9H), 3.88 (s, 3H), 7.22 (d, J=8.7 Hz, 1H), 7.55-7.64 (m, 2H), 12.41 (s, 1H); MS (ESI+) m/z 326 (M+H)+.

Workup

  1. temperaturecooled with external ice bath
  2. customwhile quenching with saturated aqueous NaHCO3 (20 mL)
  3. extractionThe aqueous layer was extracted with ethyl acetate (2×40 mL)
  4. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-d16669628df04607953a7a59ced97107
Source dataset
uspto-grants-2015_11
Patent number
US09193713B2

Reaction notes

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