User description: The synthesis of the piperazine building block of indinavir using a extra convergent, efficient, and greener method that utilized asymmetric catalysis instead of a resolution for the key intermediate 4.4.7, generic lopid is proven in Scheme 12. An Ugi multicomponent reaction provided intermediate 4.4.16, which super ed trial pack without a doctor prescription isolation was treated with triethylamine to endure elimination of HCl to afford 4.4.17. Cyclization of 4.4.17 to 4.4.18 was accomplished in 60% yield by fastidiously monitoring the response conditions and the next key asymmetric hydrogenation was achieved with 7 mol% Rh-BINAP in methanol to give 4.4.19 in quantitative yield and 97% ee.Forty Elimination of the formyl group with 35% aqueous hydrazine gave 4.4.7 in good yield with out racemization. Scheme 12. Synthesis of the piperazine portion (4.4.7) of indinavir (Crixivan). Reagents and circumstances: (a) Et3N; (b) t-BuOK; (c) 7 mol% Rh-BINAP, H2 (100 atm), MeOH, 40 °C; (d) 35% aqueous hydrazine. The synthesis of the epoxide building block 4.4.23 is shown in Scheme 13.41 Intermediate 4.4.21 was obtained in two chemical steps from cis-1-amino-indanol (4.4.20)forty two after which alkylated with allyl bromide to afford 4.4.22 in a 96:4 ratio. Scheme 13. Greener indinavir strategy: Synthesis of intermediate 4.4.23. Reagents and circumstances: (a) Ref. 42; (b) LHMDS, allyl bromide, THF, −15 °C; (c) (i) NCS, NaI, terramycin generic IPAc, aqueous NaHCO3; (ii) NaOMe, THF. Scheme 14. Convergent synthesis of indinavir (Crixivan). Reagents and methotrexate conditions: (a) IPA, generic ed soft medium pack 6 N HCl, reflux; (b) 3-picolyl chloride. generic lopid
