تفاعل #1833297

معادلة التفاعل

bendamustine hydrochloride

hexadecanol

dicyclohexylcarbodiimide

→

product

المردود 88.8%

4-{5-[Bis-(chloroethyl)-amino]-1-methyl-1H-benzimidazol-2-yl}butyric acid hexadecyl ester

المردود 88.8%

المذيبات

ظروف التفاعل

المعالجة

1. 1
   أخرىSolids were removed by vacuum filtration
2. 2
   غسيلwashed with 25 mL of MDC
3. 3
   غسيلThe filtrate was washed with saturated aqueous sodium bicarbonate solution (2×100 mL), DI water (1×100 mL) and brine (1×100 mL)
4. 4
   تجفيفbefore drying over sodium sulfate
5. 5
   ترشيحfiltering
6. 6
   تركيزconcentrating to dryness in vacuo to an off-white solid
7. 7
   أخرىThis solid was triturated with 25 mL of MDC
8. 8
   أخرىthe solid impurities were removed by vacuum filtration
9. 9
   غسيلwashed with 5 mL of MDC
10. 10
    تركيزThe filtrate was concentrated to dryness in vacuo

الإجراء التجريبي

A 250 mL three neck round bottom flask was equipped with an overhead stirrer, thermocouple, temperature controller and nitrogen sweep then charged with 10.0 g (25.34 mmol) of bendamustine hydrochloride, 6.2 g (25.6 mmol, 1.01 eq) of hexadecanol, 5.3 g (25.6 mmol, 1.01 eq) of dicyclohexylcarbodiimide (DCC), 100 mL of MDC and 0.31 g (2.54 mmol, 0.1 eq) of DMAP. The reaction was stirred at room temperature overnight at which time an in process analysis indicated the reaction was complete. Solids were removed by vacuum filtration and washed with 25 mL of MDC. The filtrate was washed with saturated aqueous sodium bicarbonate solution (2×100 mL), DI water (1×100 mL) and brine (1×100 mL) before drying over sodium sulfate, filtering and concentrating to dryness in vacuo to an off-white solid. This solid was triturated with 25 mL of MDC and the solid impurities were removed by vacuum filtration and washed with 5 mL of MDC. The filtrate was concentrated to dryness in vacuo to yield 13.1 g (22.5 mmol, 88.8%) of the product as an off-white solid with an HPLC purity of 94.0A %. 1H NMR (400 MHz, CDCl3) δ 7.17 (d, J=8.76 Hz, 1H), 7.08 (d, J=2.32 Hz, 1H), 6.78 (dd, J=2.36, 8.72 Hz, 1H), 4.05 (t, J=6.8 Hz, 2H), 3.72 (m, 4H), 3.69 (s, 3H), 3.63 (m, 4H), 2.91 (t, J=7.4 Hz, 2H), 2.49 (t, J=7.08 Hz, 2H), 2.18 (m, 2H), 1.60 (m, 2H), 1.32 (m, 26H), 0.88 (t, J=6.68 Hz, 3H).

المصدر