反応 #1583805

反応方程式

2-methyl-3-(methylthio)propanoyl chloride

TFA

pyridine

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

→

dark oil

収率 101.3%

N-(4-chloro-2-(pyridin-3-yl)thiazol-5-yl)-N,2-dimethyl-3-(methylthio)propanamide

収率 101.3%

溶媒

ACN

ACN

dichloromethane

water

water

dichloromethane

dichloromethane

反応条件

後処理

1. 1
   その他To a dry 500 ml round bottom flask equipped with magnetic stirrer
2. 2
   workup.ADDITIONwere added
3. 3
   workup.ADDITIONDuring the addition all solids
4. 4
   その他was exothermic from 20° C. to 30° C
5. 5
   workup.ADDITIONwas then added
6. 6
   その他the layers separated
7. 7
   洗浄The organic phase was washed with brine
8. 8
   乾燥dried over anhydrous magnesium sulfate
9. 9
   ろ過filtered
10. 10
    その他rotary evaporated

実験手順

To a dry 500 ml round bottom flask equipped with magnetic stirrer, thermometer, and nitrogen inlet was added 4-chloro-N-methyl-2-(pyridin-3-yl)thiazol-5-amine (22 g, 97 mmol) and dichloromethane (250 mls). The suspension was stirred at ambient temperature while pyridine (8.48 g, 107 mmol) and DMAP (1.20 g, 9.75 mmol) were added. To this suspension was added 2-methyl-3-(methylthio)propanoyl chloride (17.8 g, 117 mmol) over 5 minutes. During the addition all solids went into solution and the reaction was exothermic from 20° C. to 30° C. The reaction was stirred at ambient temperature for 16 h. The mixture was checked by HPLC (YMC AQ column 5% ACN 95% water-0.05% TFA to 95%ACN 5% water with 0.05% TFA over 20 Min @ 1.0 ml/min) which showed complete conversion of all starting material. The reaction mixture was diluted with dichloromethane and water was then added. The mixture was poured into a separatory funnel with dichloromethane and water and the layers separated. The organic phase was washed with brine, dried over anhydrous magnesium sulfate, filtered, and rotary evaporated to afford 33.6 g of a dark oil. The oil was purified on an ISCO Combiflash Rf (330 g silica gel cartridge, mobile phase A=hexane, B=ethyl acetate, gradient 0% B to 100% B over 20 minutes). The fractions were collected into 25 mls test tubes. The tubes containing the desired product were combined and the solvent removed by rotary evaporation. This afforded 22.8 g of a thick yellow liquid in 68.4% isolated yield. The entire sample crystallized and hexane (200 mls) was added to give a slurry. The slurry was vacuum filtered and the solid allowed to air dry. This gave N-(4-chloro-2-(pyridin-3-yl)thiazol-5-yl)-N,2-dimethyl-3-(methylthio)propanamide as an off-white solid; mp 75-80° C.; 1H NMR (400 MHz, CDCl3) δ 9.12 (d, J=1.4 Hz, 1H), 8.73 (d, J=3.8 Hz, 1H), 8.34-8.09 (m, 1H), 7.43 (dd, J=7.9, 4.9 Hz, 1H), 3.30 (s, 3H), 3.06-2.70 (m, 2H), 2.49 (d, J=7.4 Hz, 1H), 2.04 (s, 3H), 1.21 (d, J=6.4 Hz, 3H); 13C NMR (101 MHz, DMSO-d6) δ175.22, 162.37, 151.91, 146.53, 136.46, 134.64, 133.35, 127.98, 124.27, 37.47, 36.71, 36.47, 17.56, 15.44; Anal. Calcd. for C14H16ClN3OS2: C, 49.18; H, 4.72; N, 12.29; S, 18.76. Found: C, 49.04: H, 4.68; N, 12.29; S, 18.68.

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