Propanedioic acid, 2-(1-ethoxyethylidene)-, 1,3-diethyl ester → 7-methyl-2-morpholino-5-oxo-5H-1,3,4-thiadiazolo[3,2-a]pyrimidine-6-carboxylic acid, ethyl ester

HRID 1248189Notes

Reaction equation

HRID 1248189 reaction equation
[NH2:1][C:2]1[S:3][C:4]([N:7]2[CH2:12][CH2:11][O:10][CH2:9][CH2:8]2)=[N:5][N:6]=1.[CH2:13]([O:15][C:16](=[O:28])[C:17](=[C:23](OCC)[CH3:24])[C:18](OCC)=[O:19])[CH3:14]>COCCOCCOC>[CH3:24][C:23]1[N:1]=[C:2]2[S:3][C:4]([N:7]3[CH2:8][CH2:9][O:10][CH2:11][CH2:12]3)=[N:5][N:6]2[C:18](=[O:19])[C:17]=1[C:16]([O:15][CH2:13][CH3:14])=[O:28]

Participants

4

Reactant 2

HCID 99520Propanedioic acid, 2-(1-ethoxyethylidene)-, 1,3-diethyl esterHCID 15000115-Morpholin-4-yl-1,3,4-thiadiazol-2-amine

Product 1

HCID 133129717-methyl-2-morpholino-5-oxo-5H-1,3,4-thiadiazolo[3,2-a]pyrimidine-6-carboxylic acid, ethyl ester

Reagents, catalysts & solvents 1

HCID 8150DiglymeSolvent

Procedure

2-amino-5-morpholino-1,3,4-thiadiazole (5 g) was reacted with diethyl(1-ethoxy-ethylidene)-malonate (6.2 g) in diglyme (40 ml) at 150° C. for 20 hours. After cooling the reaction mixture was diluted with ice water and extracted with ethyl acetate; after evaporation in vacuo to dryness, the residue was purified over a SiO2 column using chloroform-methanol 98:2 as eluent. Crystallization from isopropyl ether gave 7-methyl-2-morpholino-5-oxo-5H-1,3,4-thiadiazolo[3,2-a]pyrimidine-6-carboxylic acid, ethyl ester, m.p. 196°-198° C. (2.6 g), which was reacted with 2-amino-pyridine (2.25 g) in polyphosphoric acid (130 g) under stirring at 120° C. for 4 hours. After cooling, dilution with ice water and neutralization with 35% NaOH, the precipitate was filtered and washed with water to give 1.9 g of 7-methyl-2-morpholino-5-oxo-5H-1,3,4-thiadiazolo[3,2-a]pyrimidine-6-N-(2-pyridyl)-carboxamide, m.p. 285°-287° C.

Workup

  1. temperatureAfter cooling the reaction mixture
  2. extractionextracted with ethyl acetate
  3. customafter evaporation in vacuo to dryness
  4. customthe residue was purified over a SiO2 column
  5. customCrystallization from isopropyl ether

Sources & evidence

ORD record
ord-8ca9060618544bfe88b1469ef3d467dd
Source dataset
uspto-grants-1985_06
Patent number
US04522944

Reaction notes

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