Lithium hydroxide, monohydrate → N-(3-phenyl-[1,2,4]thiadiazol-5-yl)-malonamic acid

HRID 1093697Notes

Reaction equation

HRID 1093697 reaction equation
C([O:3][C:4](=[O:20])[CH2:5][C:6]([NH:8][C:9]1[S:13][N:12]=[C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:10]=1)=[O:7])C.O[Li].O>CO.O>[C:14]1([C:11]2[N:10]=[C:9]([NH:8][C:6](=[O:7])[CH2:5][C:4]([OH:20])=[O:3])[S:13][N:12]=2)[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 66592045N-(3-phenyl-[1,2,4]thiadiazol-5-yl)-malonamic acid ethyl ester

Product 1

HCID 57874387N-(3-phenyl-[1,2,4]thiadiazol-5-yl)-malonamic acidYield 45%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a stirred solution of 3-phenyl-[1,2,4]thiadiazol-5-ylamine (0.25 g, 0.00141 mol) in chloroform (2.5 mL) was added mono ethylmalonylchloride (0.233 g, 0.00155 mol) dropwise, the resulting mixture was stirred for 3 hours. The mixture was then concentrated and the residue was stirred in ethyl acetate. The filtrate was removed and concentrated to afford 0.26 g (63%) of N-(3-phenyl-[1,2,4]thiadiazol-5-yl)-malonamic acid ethyl ester. LC-MS purity: 292.07 (M+1)+, 67%. To a solution of N-(3-phenyl-[1,2,4]thiadiazol-5-yl)-malonamic acid ethyl ester (0.26 g, 0.00089 mol) in a mixture of methanol (3 mL) and H2O (1 mL) was added LiOH.H2O (0.112 g, 0.00267 mol). The reaction mixture was stirred for 4 hours at ambient temperature then concentrated. The resulting residue was diluted with cold water, acidified with 2NHCl and the product was extracted with ethyl acetate. The ethyl acetate layer washed with brine, dried over Na2SO4 and evaporated under reduced pressure to afford 0.105 g (45%) of N-(3-phenyl-[1,2,4]thiadiazol-5-yl)-malonamic acid. LCMS: 264.27 (M+1)+: 97.64%.

Workup

  1. concentrationthen concentrated
  2. additionThe resulting residue was diluted with cold water
  3. extractionwas extracted with ethyl acetate
  4. washThe ethyl acetate layer washed with brine
  5. dry with materialdried over Na2SO4
  6. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-b7c5cb6892184e46b8350dacea59ca2e
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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