反応 #1005933

反応方程式

5-fluoro-4-imino-1-(4-methoxyphenylsulfonyl)-3-methyl-3,4-dihydropyrimidin-2(1H)-one

trifluoroacetic acid

dimethylsulfide

→

desired product

5-Fluoro-4-imino-3-methyl-3,4-dihydropyrimidin-2(1H)-one

反応条件

後処理

1. 1
   その他A 25-mL screw capped vial
2. 2
   濃縮was then concentrated to dryness by rotary evaporation at 30° C
3. 3
   workup.DISSOLUTIONThe crude material was then dissolved in a minimal amount of methanol (CH3OH; ˜2 mL)
4. 4
   洗浄rinsing the source vial with CH3OH (3×1 mL)
5. 5
   その他The solid cartridge was then dried under vacuum at room temperature
6. 6
   その他After drying
7. 7
   その他the product was purified by chromatography (4 g SiO2 column; 0 to 30% CH3OH in dichloromethane (CH2Cl2) gradient)
8. 8
   その他The material thus obtained

実験手順

A 25-mL screw capped vial was charged with 5-fluoro-4-imino-1-(4-methoxyphenylsulfonyl)-3-methyl-3,4-dihydropyrimidin-2(1H)-one (80.4 mg, 0.257 mmol), trifluoroacetic acid (TFA; 16.0 mL, 215 mmol), and dimethylsulfide (94 μL, 1.28 mmol). The resulting solution was allowed to stir at room temperature for 5.5 h and was then concentrated to dryness by rotary evaporation at 30° C. The crude material was then dissolved in a minimal amount of methanol (CH3OH; ˜2 mL) and loaded onto a 5-g normal phase solid load Isco cartridge, rinsing the source vial with CH3OH (3×1 mL). The solid cartridge was then dried under vacuum at room temperature. After drying, the product was purified by chromatography (4 g SiO2 column; 0 to 30% CH3OH in dichloromethane (CH2Cl2) gradient). The material thus obtained was determined to be the 4-methoxysulfonic acid salt of the desired product. The free base was obtained by dissolving the material in CH3OH (4 mL), adding MP-carbonate resin (345 mg, 3.03 mmol/g, 4.0 equiv), and allowing to stir at room temperature. After stirring for 20 h, the solid resin was filtered off and rinsed with CH3OH (3×1 mL). After concentration under high vacuum, 5-fluoro-4-imino-3-methyl-3,4-dihydropyrimidin-2(1H)-one (35.2 mg, 96%) was obtained as a 95% pure white solid: mp 181-184° C.; 1H NMR (400 MHz, DMSO-d6) δ 7.48 (d, J=4.1 Hz, 1H), 3.22 (s, 3H); 13C NMR (101 MHz, DMSO-d6) δ 152.19 (s), 151.86 (d, J=27.3 Hz), 136.73 (d, J=221.0 Hz), 129.45 (d, J=26.0 Hz), 28.91 (s).

出典