2-Amino-5-chlorothiazole hydrochloride → HCID 13105850, compound

HRID 1583341Notes

Reaction equation

HRID 1583341 reaction equation
Cl.[NH2:2][C:3]1[S:4][C:5]([Cl:8])=[CH:6][N:7]=1.[Cl:9][CH2:10][C:11](=O)[CH2:12][C:13]([O-])=[O:14]>>[Cl:8][C:5]1[S:4][C:3]2=[N:2][C:11]([CH2:10][Cl:9])=[CH:12][C:13](=[O:14])[N:7]2[CH:6]=1

Participants

3

Reactant 2

HCID 1487432-Amino-5-chlorothiazole hydrochlorideHCID 22066206Chloroacetoacetate

Product 1

HCID 13105850HCID 13105850, compound

Conditions

Temperature
110 °C

Procedure

2-amino-5-chloro-thiazole hydrochloride (8 g) was reacted with 4-chloroacetoacetate (15.8 g) in polyphosphoric acid (40 g) under stirring at 110° C. for 1 hour. After cooling, dilution with water and neutralization with 35% NaOH, the precipitate was filtered and washed with water. Crystallization from isopropyl ether gave 2-chloro-7-chloromethyl-5H-thiazolo[3,2-a]pyrimidine-5-one, m.p. 123°-125° C. (7.45 g), which was reacted with triphenylphosphine (9.42 g) in acetonitrile (100 ml) under stirring at reflux temperature for 10 hours. After cooling the precipitate was filtered and washed with acetonitrile to give (2-chloro-5H-thiazolo[3,2-a]pyrimidine-5-one-7-yl)-methyl-triphenylphosphonium chloride, m.p. 300°-310° C. dec. (10 g) which was suspended in dimethylsulfoxide (40 ml) and treated with potassium tert-butoxide (2.48 g) dissolved in dimethylsulfoxide (40 ml) at room temperature under stirring for 10 minutes. To the solution of the ylide so obtained 5 -formyl-2-methyl-thiazole (3.1 g) dissolved in dimethylsulfoxide (20 ml) was added and the reaction mixture was kept under stirring at room temperature for 15 minutes: after dilution with ice water and neutralization with NaH2PO4 the precipitate was filtered and crystallized from CH2Cl2 -methanol to give 3.4 g of 2-chloro-7-trans-[2-(2-methyl-5-thiazolyl)-ethenyl]-5H-thiazolo[3,2-a]pyrimidine-5-one, m.p. 224°-226° C., NMR (CDCl3) δ ppm: 2.97 (s) (3H, --CH3), 6.61 (s) (1H, C-6 proton), 6.78 (d) (1H, β-ethenyl proton), 7.82 (d) (1H, α-ethenyl proton), 7.88 (s) (1H, C-3 proton), 8.02 (s) (1H, C-4 thiazolyl proton); JHαHβ =16 Hz.

Workup

  1. temperatureAfter cooling
  2. filtrationdilution with water and neutralization with 35% NaOH, the precipitate was filtered
  3. washwashed with water
  4. customCrystallization from isopropyl ether

Sources & evidence

ORD record
ord-0e2593c9fb7945b095d7e73fdfc0fa60
Source dataset
uspto-grants-1985_11
Patent number
US04551457

Reaction notes

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