反応 #1495417

反応方程式

K2CO3

2-(5-(diethylamino)-2-(3-(16-(4-(4-hydroxyphenyl)piperazin-1-yl)-16-oxo-4,7,10,13-tetraoxahexadecyl)benzamido)phenyl)-N-(3-(trifluoromethyl)benzyl)isonicotinamide

2-(2-(2-methoxyethoxy)ethoxy)ethyl 4-methylbenzenesulfonate

Water

2-(2-(2-methoxyethoxy)ethoxy)ethyl 4-methylbenzenesulfonate

→

title compound

収率 110.4%

2-(5-(diethylamino)-2-(3-(16-(4-(4-(2-(2-(2-methoxyethoxy)ethoxy)ethyoxy)phenyl)piperazin-1-yl)-16-oxo-4,7,10,13-tetraoxahexadecyl)benzamido)phenyl)-N-(3-(trifluoromethyl)benzyl)isonicotinamide

収率 110.4%

TFA

溶媒

DMF

反応条件

後処理

1. 1
   温度The reaction mixture was cooled to room temperature
2. 2
   workup.STIRRINGThe mixture was stirred for 3 days at room temperature
3. 3
   その他5 hours
4. 4
   その他at 70° C
5. 5
   抽出extracted with DCM (3×10 mL)
6. 6
   乾燥The combined organic layers were dried (Na2SO4)
7. 7
   濃縮concentrated
8. 8
   その他Purification by reverse-phase HPLC
9. 9
   洗浄eluting with a water/ACN gradient
10. 10
    workup.ADDITIONcontaining 0.1% TFA

実験手順

Finely ground K2CO3 (54 mg, 039 mmol) was added to a solution of 2-(5-(diethylamino)-2-(3-(16-(4-(4-hydroxyphenyl)piperazin-1-yl)-16-oxo-4,7,10,13-tetraoxahexadecyl)benzamido)phenyl)-N-(3-(trifluoromethyl)benzyl)isonicotinamide (125 mg, 0.13 mmol) and 2-(2-(2-methoxyethoxy)ethoxy)ethyl 4-methylbenzenesulfonate (50 mg, 0.16 mmol) in DMF (0.30 mL), and was heated at 70° C. for 3 hours with stirring. The reaction mixture was cooled to room temperature and another portion of 2-(2-(2-methoxyethoxy)ethoxy)ethyl 4-methylbenzenesulfonate (75 mg, 0.34 mmol) was added. The mixture was stirred for 3 days at room temperature and then 5 hours at 70° C. Water (10 mL) was added to the cooled reaction mixture and extracted with DCM (3×10 mL). The combined organic layers were dried (Na2SO4) and concentrated. Purification by reverse-phase HPLC eluting with a water/ACN gradient containing 0.1% TFA gave a TFA salt of the title compound (80 mg). 1H NMR (400 MHz, CD3OD, ppm) δ 9.44 (t, J=5.0 Hz, 0.6H), 8.93 (dd, JAB=5.3 Hz, JAC=0.6 Hz, 1H), 8.84 (d, J=9.0 Hz, 1H), 8.40 (s, 1H), 8.09 (d, J=2.5 Hz, 1H), 7.88 (dd, JAB=5.1 Hz. JAC=0.5 Hz, 1H), 7.80 (m, 2H), 7.69 (s, 1H), 7.65-7.52 (m, 4H), 7.47 (dd, JAB=4.1 Hz, JAC=1.2 Hz, 2H), 7.09 (d, J=9.0 Hz, 2H), 6.88 (d, J=9.2 Hz), 4.69 (d, J=4.3 Hz 2H), 4.04 (m, 2H), 3.78-3.68 (m, 12H), 3.66-3.63 (m, 2H), 3.62-3.52 (m, 16H), 3.51-3.45 (m, 4H), 3.31 (s, 3H), 3.22 (t, J=4.1 Hz, 2H), 3.16 (t, J=4.1 Hz, 2H), 2.80 (t, J=7.4 Hz, 2H), 2.64 (t, J=6.3 Hz, 2H), 1.91 (m, 2H), 1.20 (t, J=7.1 Hz, 6H). MS (ES, m/z): 1115.4 [M+H]+.

出典