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US 5,627,278 AGranted
Process for preparing compounds containing a fused bicyclic ring
AssigneeBristol-Myers Squibb Company
InventorJeffrey A. Robl
Life of this patent
Estimating the term…
Abstract
A process for preparing compounds of the formula ##STR1## wherein X is O or S; n is one or two; m is zero or one; Y is CH.sub.2, O, or S provided that Y is O or S only when m is one; and A is ##STR2## is disclosed. Also disclosed are processes for preparing the corresponding amino intermediates.
Claims10
A process for preparing the compounds of the formula ##STR84## wherein:
- A is ##STR85## X is O or S;
- R.sub.1 and R.sub.12 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, substituted alkyl, substituted alkenyl, aryl, substituted aryl, heteroaryl, cycloalkyl-alkylene-, aryl-alkylene-, substituted aryl-alkylene-, and heteroaryl-alkylene- or R.sub.1 and R.sub.12 taken together with the carbon to which they are attached complete a cycloalkyl ring or a benzofused cycloalkyl ring;
- R.sub.3, R.sub.5 and R.sub.7 are independently selected from the group consisting of hydrogen and an acid protecting group;
- R.sub.4 is alkyl, cycloalkyl-(CH.sub.2).sub.p --, substituted alkyl, aryl-(CH.sub.2).sub.p --, substituted aryl-(CH.sub.2).sub.p --, or heteroaryl-(CH.sub.2).sub.p --;
- R.sub.6 is alkyl, substituted alkyl, cycloalkyl-(CH.sub.2).sub.p --, aryl-(CH.sub.2).sub.p --, substituted aryl-(CH.sub.2).sub.p --, or heteroaryl-(CH.sub.2).sub.p --;
- m is zero or one;
- Y is CH.sub.2, S, or O provided that Y is S or O only when m is one;
- n is one or two;
- p is zero or an integer from 1 to 6;
- q is zero or an integer from 1 to 3;
- and
- r is zero or one;
- which comprises
- a) when A is ##STR86## coupling the acylmercapto sidechain of the formula ##STR87## or an activated form thereof with the amine of the formula ##STR88## in the presence of a coupling reagent;
- b) when A is ##STR89## and R.sub.3 is hydrogen, treating the product from part (a) to remove the acyl group R.sub.6 --C(O)-- and the R.sub.3 acid protecting group;
- c) when A is ##STR90## coupling the carboxylic acid of the formula ##STR91## or an activated form thereof with the amine of the formula ##STR92## in the presence of a coupling reagent;
- d) when A is ##STR93## and R.sub.3 is hydrogen, reacting the keto acid or ester of the formula ##STR94## under reducing conditions or the triflate of the formula ##STR95## with the amine of the formula ##STR96## followed by removal of the R.sub.3 acid protecting group;
- or e) when A is ##STR97## and R.sub.3 is hydrogen, coupling a phosphonochloridate of the formula ##STR98## with the amine of the formula ##STR99## followed by removal of the R.sub.3 and R.sub.5 acid protecting groups.
15 more elements
A process for preparing the compounds of the formula ##STR102## wherein:
- X is O or S;
- n is one or two;
- m is zero or one;
- Y is CH.sub.2, O or S provided that Y is O or S only when m is one;
- and
- R.sub.3 is an acid protecting group;
- which comprises:
- a) coupling an amino acid of the formula ##STR103## with the amino acid ester of the formula ##STR104## to give the dipeptide ##STR105## wherein:
- P.sub.1 is an amino protecting group or a group which together with the N-atom forms a protecting group;
- and
- P.sub.2 is a hydroxy or mercapto protecting group;
- b) selectively removing the P.sub.2 protecting group from the product of part (a);
- c) cyclizing the product of part (b) to give ##STR106## and d) removing the P.sub.1 protecting group of the product of part (c) to give the desired product.
10 more elements
A process for preparing the compounds of the formula ##STR117## wherein:
- X is O or S;
- n is one or two;
- m is zero or one;
- and
- R.sub.3 is an acid protecting group;
- which comprises:
- a) coupling an amino acid of the formula ##STR118## with the hydroxy amino acid ester of the formula ##STR119## to give the dipeptide of the formula ##STR120## wherein:
- P.sub.1 is an amino protecting group or a group which together with the N-atom forms a protecting group;
- and
- P.sub.2 is a hydroxy or mercapto protecting group;
- b) oxidizing the hydroxy product of part (a) to the aldehyde of the formula ##STR121## c) selectively removing the P.sub.2 protecting group from the aldehyde product of part (b);
- d) cyclizing the product of part (c) to give ##STR122## e) removing the P.sub.1 protecting group of the product of part (d) to give the desired product.
9 more elements
Dependencies are inferred from the claim text.