Non-nucleoside reverse transcriptase inhibitors

A method to prepare compounds according to formula (I)

• where
• R2 is an optionally nitrogen-containing heterocycle, wherein the nitrogen is located at the 2 position relative to the urea bond;
• R3 is H or C1-C3 alkyl
• R4-R7 are independently selected from H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, haloC1-C6 alkyl, C1-C6 alkanoyl, haloC1-C6 alkanoyl, C1-C6 alkoxy, haloC1-C6 alkoxy, C1-C6 alkyloxy-C1-C6 alkyl, haloC1-C6 alkyloxy-C1-C6 alkyl hydroxy-C1-C6 alkyl, amino-C1-C6 alkyl, carboxy-C1-C6 alkyl, cyano-C1-C6 alkyl, amino, carboxy, carbamoyl, cyano, halo, hydroxy;
• comprising taking a compound of formula (V)
• where
• R4 and R7 are independently halo, PG is lower alkyl, PG* is lower alkyl or together with the adjacent O defines a keto group through the steps of:
• i) optionally transform PG* to define a keto group by treatment of a compound of formula (V) wherein PG* is an hydroxy protecting group with Jone's reagent;
• iia) reaction of a compound of formula (V) wherein PG* together with the adjacent O defines a keto group with BBr3 in dichloromethane followed by addition of acetonitrile and finally sodium hydroxide to give the chromenecyclopropylcarboxylic acid;
• iib) alternatively, ring-opening of a compound of formula (V) wherein PG* together with the adjacent O defines a keto group, with HBr in conjuction with AcOH followed by subjection to NaGH to give the chromenecyclopropylcarboxylic acid;
• iii) conversion of the acid to the corresponding acyl azide by treatment with DPPA followed by a Curtius rearrangement to the isocyanate;
• iv) coupling of the isocyanate with the relevantly substituted 2-aminopyridine.