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The molecularity of an elementary reaction is the number of molecules that collide during that step in the mechanism. If there is only a single reactant molecule in an elementary reaction, that step is designated as unimolecular.151038-94-7, name is 6-(2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanehydrazide 2,2,2-trifluoroacetate. A new synthetic method of this compound is introduced below., 151038-94-7
[00247] Acetoxyoxaliplatin(4-acetylphenyl)carbamate was first synthesized using acetoxy(hydroxyl)oxaliplatin (243 mg, 0.51 mmol, 1 .00 equiv) and 4- acetylphenylisocyanate (124 mg, 0.77 mmol, 1 .50 equiv) dissolved in DMF (0.1 M, 5 mL). The reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated and impregnated on silica gel. The crude product was purified by normal phase chromatography using silica gel column (40 g) eluted with 5-20% MeOH / CH2CI2 gradient over 15 minutes. Pure fractions were combined and concentrated under vacuum to provide the product as a yellow solid (241 mg, 74%, 83% pure). HPLC-MS 83.1 %, m/z for CigHzsNsOgPt +H)+] = 635.2. 16 [00248] Synthesis of acetate 4-(1-(2-(6-(2,5-dioxo-2H-pyrrol-1(5H)- l)hexanoyl)hydrazono)ethyl) phenyl carbamate oxaliplatin: Acetoxyoxalplatin(4- acetylphenyl)carbamate (228 mg, 0.36 mmol, 1 .00 equiv) was dissolved in DMF (0.05 M, 7 mL) and treated with 6-(2,5-dioxo-2,5-dihydro-1 H-pyrrol-1 – yl)hexanehydrazide TFA salt (158 mg, 0.47 mmol, 1 .30 equiv). The reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was concentrated and the residue was triturated with acetonitrile to precipitate the product as a yellow powder. This powder was triturated first with isopropyl alcohol (iPrOH) and then with DCM to afford the desired product (70 mg, 23%, 93.5% pure). HPLC-MS 93.5%, m/z for CzgHssNeOu Pt [(M+H)+] = 842.3. 1 H NMR (500 MHz, DMF-d7) 5 10.34-10.15 (m, 1 H), 9.91 -9.66 (m, 1 H), 9.37-9.24 (m, 1 H), 8.88-8.66 (m, 2H), 8.59-8.48 (m, 1 H), 7.80-7.73 (m, 2H), 7.61 -7.53 (m, 2H), 7.04-6.98 (m, 2H), 3.50-3.43 (m, 2H), 3.14-3.02 (m, 1 H), 2.75-2.70 (m, 1 H), 2.43-2.25 (m, 6H), 2.01 -1 .92 (m, 3H), 1 .74-1 .53 (m, 9H), 1 .42-1 .24 (m, 4H)., 151038-94-7
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Reference£º
Patent; BLEND THERAPEUTICS, INC.; MOREAU, Benoit; BILODEAU, Mark T.; WHALEN, Kerry; MEETZE, Kristan; SINGH, Sukhjeet; WOOSTER, Richard; LEMELIN, Charles-Andre; (139 pag.)WO2015/200250; (2015); A1;,
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