合成路线1

Cyclocondensation of ethyl 3-amino-4-methyl-2-thiophenecarboxylate (I) with urea (II) at 190 °C gives 7-methylthieno[3,2-d]pyrimidine-2,4-dione (III), which is chlorinated with POCl3 at reflux to yield 2,4-dichloro-7-methylthieno[3,2-d]pyrimidine (IV). Condensation of compound (IV) with morpholine (V) in MeoH affords 2-chloro-7-methyl-4-(4-morpholinyl)thieno[3,2-d]pyrimidine (VI) , which, after metalation with BuLi in THF, is formylated with DMF, providing the thieno[3,2-d]pyrimidine-6-carbaldehyde derivative (VII) . Reductive amination of aldehyde (VII) with N-Boc-piperazine (VIII) in the presence of HC(oMe)3, AcoH and naBH(oAc)3 in dichloroethane gives the piperazinylmethyl derivative (IX) , which by cleavage of the Boc moiety by means of HCl in CH2Cl2 produces the N-deprotected piperazine derivative (X). N-Acylation of compound (X) with (S)-lactic acid (XI) in the presence of HATU and DIEA in DMF generates the corresponding amide (XII), which is finally submitted to Suzuki coupling with the boronate ester (XIII) in the presence of PdCl2(PPh3)4 and Na2CO3 or K2CO3 in acetonitrile .
Alternatively, Suzuki coupling of chloro intermediate (IX) with boronate ester (XIII) in the presence of PdCl2(PPh3)2 and Na2CO3 in acetonitrile under microwave irradiation produces the 2-aminopyrimidine derivative (XIV), which is then N-deprotected by means of HCl in CH2Cl2 to yield the free piperazine derivative (XV). Finally, piperazine derivative (XV) is condensed with (S)-lactic acid (XI) in the presence of DIEA and HATU in DMF .