Neprilysin inhibitors
In one aspect, the invention relates to compounds having the formula: where X, R a , R b , R 2 , and R 7 are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds are prodrugs of compounds having neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising these compounds; methods of using these compounds; and processes and intermediates for preparing these compounds.
1. A method of making Compound 6N:
or a pharmaceutically acceptable salt thereof, comprising:
contacting Compound 2:
with palladium on carbon and hydrogen gas under conditions sufficient to provide Compound 6N or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 , further comprising contacting Compound 1:
with 3-hydroxyisoxazole-5-carboxylic acid under conditions sufficient to provide Compound 2.
3. The method of claim 2 , further comprising contacting a compound having the structure:
with hydrochloric acid under conditions sufficient to provide Compound 1.
4. The method of claim 1 , wherein the conditions comprise ethyl acetate and acetic acid.
5. The method of claim 2 , wherein the conditions further comprise N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate and N-ethyl-N-isopropylpropan-2-amine.
6. The method of claim 3 , wherein the conditions comprise acetonitrile and dioxane.