Antifolate chemistry: synthesis of 4-[N-[(6RS)-2-methyl-4-oxo-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl]-N-(prop-2-ynyl)amino]benzoic acid via a (propargyl)Co2(CO)6+ complex.
A new route to compound 3 (4-[N-(6RS)-2-methyl-4-oxo-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl]-N-(prop-2-ynyl)amino]benzoic acid), a crucial intermediate for the synthesis of potent inhibitors of thymidylate synthase (TS), is described. In this sequence the C6-N10 bond was constructed first, by the reductive amination of 5-acetamido-6-bromoindan-1-one 6 with tert-butyl 4-aminobenzoate, then the cyclopenta[g]quinazolinone ring was formed and the propargyl group was introduced on the N10-position using the (propargyl)Co2(CO)6+ complex as the electrophilic propargyl reagent.
Bavetsias
Vassilios
V
Cancer Research UK Centre for Cancer Therapeutics at The Institute of Cancer Research, Chemistry Department, Cancer Research UK Laboratory, 15 Cotswold Road, Sutton, Surrey, UK SM2 5NG. vassilio@icr.ac.uk
Clauss
Rainer
R
Henderson
Elisa A
EA
D000480:Alkynes / Q000737:chemistry*; D001565:Benzoates / Q000138:chemical synthesis* / Q000737:chemistry; D003035:Cobalt / Q000737:chemistry*; D005493:Folic Acid Antagonists / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors
D000480:Alkynes; D001565:Benzoates; D005493:Folic Acid Antagonists; D009942:Organometallic Compounds; D011799:Quinazolines; D003035:Cobalt; D013940:Thymidylate Synthase