반응 #1583804

반응 방정식

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

acetonitrile

phosphorus oxychloride

→

solid

수율 75.0%

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

수율 75.0%

용매

ethyl acetate

—

hexanes

반응 조건

후처리

1. 1
   기타To a dry 2 L round bottom flask equipped with mechanical stirrer, addition funnel
2. 2
   온도reflux condenser
3. 3
   기타occurred from 22° C. to 34° C
4. 4
   온도The reaction mixture was heated to 85° C. (
5. 5
   온도refluxing gently)
6. 6
   workup.WAITAfter 3 hours
7. 7
   workup.DISSOLUTIONall of the solid had dissolved
8. 8
   기타forming a dark amber solution
9. 9
   온도to cool to 25° C.
10. 10
    기타the 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
    기타to form after a few minutes
14. 14
    workup.STIRRINGto stir at 25° C. for 16 hours
15. 15
    여과The brown solid was collected by vacuum filtration
16. 16
    세척washed with water
17. 17
    기타This gave a tan solid wet cake (91 g) which
18. 18
    기타was then dried in vacuo at 40° C. to a constant weight

실험 절차

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.

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