Organic Chemistry of Drug Synthesis. Volume 7

with the benzylic halide on the tetrazole-substituted biphenyl ( 246 )to
afford the alkylated product ( 247 ). Saponfication of the ester and
removal of the triphenylmethyl protecting group compeles the synthesis
of the angiotensin antagonistolmesartan( 248 ).^35

NC

NC NH 2

NH 2

242

+

(CH 3 O) 3 C

NH

NC N

NC

243

1. NaOH


2. CH 3 CH 2 OH NH

C 2 H 5 O 3 C N

C 2 H 5 O 2 C

244

CH 3 MgBr

NH

N

C 2 H 5 O 2 C

HO

CH 3

H 3 C

245

Br

NC(C 6 H 5 ) 3

N N

N

246

NC(C 6 H 5 ) 3

NN

N

247

N

C 2 H 5 O 2 C

HO

CH 3

H 3 C

1. NaOH

NH

N N

N

248

HO 2 C

HO

CH 3

H 3 C

2. H 2

N

N N

REFERENCES

1. E.B. Villhauer, J.A. Brinkman, G.B. Nader, B.F. Burkey, B.E. Dunning,
   K. Prasad, B.L. Mangold, M.E. Russel, T.A. Hughes,J. Med. Chem. 46 ,
   2774 (2003).


2. S.J. Coutts et al.,J. Med. Chem. 39 , 2087 (1996).


3. S.J. Wittenberger, M.A. McLaughlin.Tetrahedron Lett. 40 , 7175 (1999).


4. P.E. Cross, A.R. MacKenzie, U.S. Patent 5,096,890 (1992).


5. M.M. Faul, E. Kobierski, M.E. Kopach,J. Org. Chem. 68 , 5739 (2003).


6. W.F. Heath, J.H. McDonald, M. Paal, T. Schotten, W. Stenzel, U.S. Patent
   5,672,618 (1997).


7. M.M. Faul, J.R. Gillig, M.R. Jirousek, L.M. Ballas, T. Schotten, A. Kahl,
   M. Mohr,Bioorg. Med. Chem. Lett. 13 , 1857 (2003).


8. C.D.W. Brooks et al.,J. Med. Chem. 38 , 4768 (1995).


9. J. Haruta, H. Hashimoto, M. Matsushita, U.S. Patent 5,994,381 (1999).


10. J.J. Talley et al.,J. Med. Chem. 43 , 775 (2000).


11. J.J. Talley et al.,J. Med. Chem. 43 , 1661 (2000).

112 FIVE-MEMBERED HETEROCYCLES