反応 #1583804

反応方程式

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

acetonitrile

phosphorus oxychloride

→

solid

収率 75.0%

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

収率 75.0%

溶媒

ethyl acetate

—

hexanes

反応条件

後処理

1. 1
   その他To a dry 2 L round bottom flask equipped with mechanical stirrer, addition funnel
2. 2
   温度reflux condenser
3. 3
   その他occurred from 22° C. to 34° C
4. 4
   温度The reaction mixture was heated to 85° C. (
5. 5
   温度refluxing gently)
6. 6
   workup.WAITAfter 3 hours
7. 7
   workup.DISSOLUTIONall of the solid had dissolved
8. 8
   その他forming a dark amber solution
9. 9
   温度to cool to 25° C.
10. 10
    その他the 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
    その他to form after a few minutes
14. 14
    workup.STIRRINGto stir at 25° C. for 16 hours
15. 15
    ろ過The brown solid was collected by vacuum filtration
16. 16
    洗浄washed with water
17. 17
    その他This gave a tan solid wet cake (91 g) which
18. 18
    その他was then dried in vacuo at 40° C. to a constant weight

実験手順

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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