Reacción #1583804

Ecuación de reacción

N-methyl-2-(pyridine-3-carbothioamido)acetamide

acetonitrile

phosphorus oxychloride

→

solid

Rendimiento 75.0%

N-methyl-2-(pyridin-3-yl)thiazol-5-amine

Rendimiento 75.0%

Disolventes

ethyl acetate

—

hexanes

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroTo a dry 2 L round bottom flask equipped with mechanical stirrer, addition funnel
2. 2
   Temperaturareflux condenser
3. 3
   Otrooccurred from 22° C. to 34° C
4. 4
   TemperaturaThe reaction mixture was heated to 85° C. (
5. 5
   Temperaturarefluxing gently)
6. 6
   workup.WAITAfter 3 hours
7. 7
   workup.DISSOLUTIONall of the solid had dissolved
8. 8
   Otroforming a dark amber solution
9. 9
   Temperaturato cool to 25° C.
10. 10
    Otrothe solvent removed by rotary evaporation
11. 11
    workup.DISSOLUTIONThe residue was dissolved in water
12. 12
    workup.ADDITIONtreated with solid sodium bicarbonate until slightly basic (pH˜8) with continuous stirring
13. 13
    Otroto form after a few minutes
14. 14
    workup.STIRRINGto stir at 25° C. for 16 hours
15. 15
    FiltraciónThe brown solid was collected by vacuum filtration
16. 16
    Lavadowashed with water
17. 17
    OtroThis gave a tan solid wet cake (91 g) which
18. 18
    Otrowas then dried in vacuo at 40° C. to a constant weight

Procedimiento

To a dry 2 L round bottom flask equipped with mechanical stirrer, addition funnel and reflux condenser was charged N-methyl-2-(pyridine-3-carbothioamido)acetamide (100 g, 478 mmol) and acetonitrile (1 L). To this mixture was added phosphorus oxychloride (256 g, 1672 mmol) portionwise over 10 minutes. The reaction mixture was stirred at ambient temperature for 10 minutes during which time a slight exotherm occurred from 22° C. to 34° C. The reaction mixture was heated to 85° C. (refluxing gently). After 3 hours, all of the solid had dissolved, forming a dark amber solution. Analysis of an aliquot by TLC (70% ethyl acetate : 30% hexanes) after 4 hours indicated that the reaction was essentially complete. The reaction mixture was allowed to cool to 25° C. and the solvent removed by rotary evaporation. The residue was dissolved in water and treated with solid sodium bicarbonate until slightly basic (pH˜8) with continuous stirring. A brown precipitate started to form after a few minutes. The mixture was continued to stir at 25° C. for 16 hours. The brown solid was collected by vacuum filtration and washed with water. This gave a tan solid wet cake (91 g) which was then dried in vacuo at 40° C. to a constant weight. This gave N-methyl-2-(pyridin-3-yl)thiazol-5-amine as a sand colored solid (68.5 g, 75% yield); mp 140-141° C.; 1H NMR (400 MHz, CDCl3) δ 8.98 (dd, J=2.3, 0.7 Hz, 1H), 8.53 (dd, J=4.8, 1.6 Hz, 1H), 8.07 (ddd, J=8.0, 2.2, 1.7 Hz, 1H), 7.40-7.21 (m, 1H), 6.96 (s, 1H), 4.18 (s, 1H), 2.96 (s, 3H); 13C NMR (101 MHz, CDCl3) δ153.23, 149.15, 146.54, 132.23, 130.47, 123.65, 121.20, 34.48; Anal. Calc'd. for C9H9N3S: C, 56.52; H, 4.74; N, 21.97; S, 16.77. Found: C, 56.31: H, 4.74; N, 21.81; S, 16.96.

Fuente