Reparation of AECM-MeC. Nonetheless, to assess which situations were most ing
Reparation of AECM-MeC. Nonetheless, to assess which situations had been most ing AECM-MeU nucleoside intermediate, we assumed that equivalent situations could be suitable for this substrate, a screen of unique bases and to assess which circumstances have been applied for the preparation of AECM-MeC. Nonetheless,solvents was performed (Table 3). most suitable for this substrate, a screen of diverse bases and solvents was performed (Error! Reference supply not discovered.).Molecules 2021, 26,7 ofTable three. Screen for appropriate situations for 2′-OH alkylation of 5-methyl cytidine intermediate.No. 1. two. 3. four. five. 6. 7. Methyl 2Bromoacetate two equiv. 2 equiv. 2 equiv. 2 equiv. two equiv. 2 equiv. 2 equiv. Solvent, 5 Vol heptane DCM MeCN Heptane DCM MeCN DCM/heptane (five vol), (1:four) (v/v) DCM/heptane (10 vol), (1:four) (v/v) Base K2 CO3 , 4 equiv. K2 CO3 , 4 equiv. K2 CO3 , four equiv. K3 PO4 , 2 equiv. K3 PO4 , 2 equiv. K3 PO4 , two equiv. K3 PO4 , 2 equiv. K3 PO4 , 2 equiv. (PTC) Catalyst, 0.05 Equiv. TBABr, 0.05 equiv. TBABr, 0.05 equiv. TBABr, 0.05 equiv. TBABr, 0.05 equiv. TBABr, 0.05 equiv. TBABr, 0.05 equiv. TBABr, 0.02 equiv. HPLC Location , Conver., RT, 1h 0 0 eight 0 7 32 0 HPLC Area , Conver., RT, Overnight 24 63 42 89 HPLC Region , Conver., 50 C, 3.5 h 29 35 62 42 56 90 898.two equiv.TBABr, 0.02 equiv.0-94 Impurities in HPLC profile.The PTC catalyst for two -OH alkylation of the 5-methyl cytidine derivative remained the identical. Also, a few distinctive solvents were screened (Table three) and also the final results showed that both MeCN and heptane is often suitable solvents for two -OH alkylation on the protected MeC intermediate 9. On the other hand, because the beginning compound was only partially soluble in heptane and due to difficulties with all the solubility with the final solution, the conclusion was to try the identical solvent method as for MeU (heptane/DCM mixture). Certainly, this gave a clean reaction and 94 conversion (Table three, entry eight). Moreover, although K2 CO3 was performing FM4-64 supplier nicely as a base, it turned out that the reaction was even faster and cleaner when K3 PO4 was employed as base for 5-methyl cytidine two -alkylation (Table three, entries four). As K3 PO4 and DCM/heptane proved to provide one of the most preferred outcome when it comes to yield and impurity profile, these circumstances had been made use of to upscale the reaction to 50 g of 8. Regardless of rising the temperature to 40 C, in an effort to shorten the general reaction time, the decreased grinding impact in the magnet on a larger scale gave a reaction that still essential approx. 50 h to go to completion at the same time because the addition of further reagents. Crude alkylated compound ten was reacted with ethylenediamine in methyl-THF to offer intermediate 11 (which includes removal on the exocyclic amine guarding group) followed by washes making use of NH4 Cl (aq.) to take away the excess of ethylenediamine. Then, crude 11 was subsequently treated with ethyl trifluoroacetate in methanol to afford compound 12. The exocyclic amino group was acetylated to give 13. Nevertheless, this step, following a process for the corresponding AECM-C utilizing acetic anhydride in pyridine [26,28], proved to call for much more focus as we observed about 20 of bis acetylated side item. Decreased added amounts of Ac2 O did not strengthen the outcome as we noticed that the bis acetylated solution forms in parallel together with the desired mono acetylated compound. Because of this, we performed another screen to test distinct situations for acetylation (unique solvents, Tasisulam sodium different amounts of Ac2 O, different reaction t.