ChemicalBook CAS DataBase List Rapamycin

Rapamycin synthesis

10synthesis methods

Product Name:Rapamycin
CAS Number:53123-88-9
Molecular formula:C51H79NO13
Molecular Weight:914.17

331810-10-7
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1111-92-8
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572924-54-0
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$36.00/1mg

53123-88-9
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$9.00/10mg

Yield:572924-54-0 81.03 %Chromat. ，53123-88-9 5.14 %Chromat.

Reaction Conditions:

Stage #1: 31-(trimethylsilylether)rapamycinwith 3,5-Lutidine in dichloromethane at 0 - 5; for 1.08333 h;Inert atmosphere;
Stage #2: dimethylphosphinic acid chloride in dichloromethane at 0 - 5; for 1 h;Inert atmosphere;

Steps:

5 Preparation of 42-(dimethylphosphinate) Rapamycin(Ridaforolmus) (1) using 31-trimethyisilylether Rapamycin (V-a) as a Starting Material

To a flask containing 31-trimethylsilylether Rapamycin (V-a) (300 mg, 0.304 mmole) was added dichloromethane (2 mL) under a stream of N_2(g). The resulting solution was stirred until 31-trimethylsilylether Rapamycin (V-a) was completely dissolved and cooled to 0-5° C. Next, a mixture of 3,5-lutidine (72 mg, 0.67 mmole) and dichloromethane (1 mL) was added therein dropwise over a period of more than 5 min. Then, a mixture of dimethylphosphinic chloride (DMP-Cl) (144 mg, 1.22 mmole) and dichloromethane (1 mL) was added therein dropwise over a period of more than 5 min. The resulting solution was kept at 0-5° C. for 1 hr, and monitored with HPLC. To the resulting solution was added ethyl acetate (40 mL) dropwise, followed by ethyl acetate until the final volume thereof was 300 mL. The resulting solution was successively washed with a NaHCO₃saturated solution (100 mL), an iced HCl solution (0.5 N. 100 mL), a NaHCO₃saturated solution (100 mL) and a NaCl saturated solution (100 mL), then the organic layer was dried over anhydrous sodium sulfate and concentrated to obtain a crude product of 42-(dimethylphosphinate) Rapamycin (Ridaforolimus) (I) (314 mg). The HPLC analysis data indicated that the crude product contained 81.03% (area %) of 42-(dimethylphosphinate) Rapamycin (Ridaforolimus) (I), 5.14% of Rapamycin (II), 0.54% of 31,42-bis(dimethyl phosphinate) Rapamycin (III), and 2.5% of 42-(dimethylphosphinate)-31-trimethylsilylether Rapamycin (VI-a).

References:

US2014/58081,2014,A1 Location in patent:Paragraph 0047