Ethyl 4-chloroacetoacetate → 7-chloromethyl-2-phenyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidine-5-one

HRID 485763Notes

Reaction equation

HRID 485763 reaction equation
[NH2:1][C:2]1[S:3][C:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:5][N:6]=1.[Cl:13][CH2:14][C:15](=O)[CH2:16][C:17](OCC)=[O:18]>>[Cl:13][CH2:14][C:15]1[N:1]=[C:2]2[S:3][C:4]([C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=3)=[N:5][N:6]2[C:17](=[O:18])[CH:16]=1

Participants

3

Reactant 2

HCID 69484Ethyl 4-chloroacetoacetateHCID 2194082-Amino-5-phenyl-1,3,4-thiadiazole

Product 1

HCID 131882067-chloromethyl-2-phenyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidine-5-one

Conditions

Temperature
100 °C

Procedure

2-amino-5-phenyl-1,3,4-thiadiazole (10 g) was reacted with ethyl 4-chloro-acetoacetate (18.6 g) in polyphosphoric acid (100 g) under stirring at 100° C. for 1 hour. After cooling, dilution with ice water and neutralization with 35% NaOH, the precipitate was filtered and washed with water until neutral: crystallization from methanol gave 7-chloromethyl-2-phenyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidine-5-one, m.p. 201°-202° C. (11.6 g), which was reacted with triphenylphosphine (12.4 g) in acetonitrile (500 ml) under stirring at reflux temperature for 48 hours. After cooling the precipitate was filtered and washed with isopropyl ether to give (5-oxo-2-phenyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidine-7-yl)-methyl-triphenylphosphonium chloride, m.p. 295°-300° C. (20 g), which was suspended in dimethylsulphoxide (100 ml) and treated dropwise with potassium terbutoxide (5 g) dissolved in dimethylsulphoxide (100 ml) at a temperature of about 20° C. The solution of the ylide so obtained was then reacted with benzaldehyde (4.55 g) at room temperature for 90 minutes. After dilution with ice water the precipitate was filtered and washed with water: crystallization from methanol gave 5.1 g of 2-phenyl-7-trans-(2-phenyl-ethenyl)-5H-1,3,4-thiadiazolo[3,2-a]pyrimidine-5-one, m.p. 217°-219° C., N.M.R. (CDCl3) δp.p.m.: 6.34 (s) (1H, C-6-proton), 6.82 (d) (1H, β-ethenyl proton), 7.58 (d) (1H,α-ethenyl proton), 7.12-7.98 (m) (10H, phenyl protons); JHαHβ =16 Hz.

Workup

  1. temperatureAfter cooling
  2. filtrationdilution with ice water and neutralization with 35% NaOH, the precipitate was filtered
  3. washwashed with water until neutral:
  4. customcrystallization from methanol

Sources & evidence

ORD record
ord-d7e7bfac120f43f9908707b2362e05c6
Source dataset
uspto-grants-1985_08
Patent number
US04537962

Reaction notes

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