Process for the solid phase synthesis of aldehyde, ketone, oxime, amine, hydroxamic acid and α,β-unsaturated carboxylic acid and aldehyde compounds

A process for preparing a hydroxamic acid compound of formula

• wherein
• A2 is a direct bond, alkylene, or NR13;
• R13 is hydrogen or alkyl;
• R9 is -L1-R14 or -L2-R15;
• L1 is a direct bond or alkylene;
• R14 is hydrogen, aryl, carboxy, cyano, cycloalkyl, cycloalkenyl, cyclocarbamoylalkyl, cycloimidylalkyl, heterocyclyl, heteroaryl, —NH—C(═O)—NH2, (N-carbamoyl)cyclic amine, —C═N—O—C(═O)—NH2, —C(═O)—NY1Y2, —NY1SO2aryl, —NHR13, —SR13 or —OR13;
• L2 is alkenylene or alkynylene;
• R15 is hydrogen, aryl, carboxy, cyano, cycloalkyl, cycloalkenyl, heterocyclylalkyl or heteroaryl;
• R10 and R12 are independently hydrogen or alkyl;
• or R10 and R12 together form a bond, or R10 and R9 taken together with the carbon atom through which R10 and R9 are attached form spirocycloalkyl;
• R11 is a group -L3-R16, or R11 and R9 taken together with the carbon atoms through which R11 and R9 are attached form cycloalkylene;
• or R11 and R12 taken together with the carbon atom through which R11 and R12 are attached form spirocycloalkyl;
• L3 is a direct bond, alkylene, alkenylene or alkynylene;
• R16 is hydrogen, cycloalkyl, cycloalkenyl, heterocyclyl, heterocyclenyl, aryl, heteroaryl, fused arylcycloalkyl, fused heteroarylcycloalkyl, fused arylcycloalkenyl, fused heteroarylcycloalkenyl, fused arylheterocyclyl, fused heteroarylheterocyclyl, fused arylheterocyclenyl, fused heteroarylheterocyclenyl, fused cycloalkenylaryl, fused cycloalkylaryl, fused heterocyclylaryl, fused heterocyclenylaryl, fused cycloalkylheteroaryl, fused cycloalkenylheteroaryl, fused heterocyclenylheteroaryl, fused heterocyclylheteroaryl, —NH—C(═O)—NH2, —C═N—O—C(═O)—NH2, —C(═O)—NY1Y2;
• —NY1SO2aryl, —NR13, —SR13, or —OR13;
• Y1 and Y2 are independently selected from hydrogen, alkyl, aralkyl, and aryl, or Y1 and Y2 taken together with the nitrogen atom to which Y1 and Y2 are attached form azaheterocyclyl;
• Ar is selected from the group of formulae
• R17 is alkyl, or, when Z3 is a direct bond, then R17 is hydrogen, alkyl, alkenyl or alkynyl;
• R18 is cycloalkyl, cycloalkenyl, heterocyclyl, heterocyclenyl, aryl, heteroaryl, fused arylcycloalkyl, fused heteroarylcycloalkyl, fused arylcycloalkenyl, fused heteroarylcycloalkenyl, fused arylheterocyclyl, fused heteroarylheterocyclyl, fused arylheterocyclenyl, fused heteroarylheterocyclenyl, fused cycloalkenylaryl, fused cycloalkylaryl, fused heterocyclylaryl, fused heterocyclenylaryl, fused cycloalkylheteroaryl, fused cycloalkenylheteroaryl, fused heterocyclenylheteroaryl or fused heterocyclylheteroaryl;
• R19 is R20, —OR20, —SR20, —SOR20, SO2R20, —SO2NR20R21, —NR20SO2R21, —NR20R21, —O(C═O)NR20R21, —NR20C(═O)R21, —N(OH)C(═O)R20, or —C(═O)N(OH)R21,
• R20 and R21 are independently hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, heterocyclyl, heterocyclenyl, aryl, heteroaryl, fused arylcycloalkyl, fused heteroarylcycloalkyl, fused arylcycloalkenyl, fused heteroarylcycloalkenyl, fused arylheterocyclyl, fused heteroarylheterocyclyl, fused arylheterocyclenyl, fused heteroarylheterocyclenyl, fused cycloalkenylaryl, fused cycloalkylaryl, fused heterocyclylaryl, fused heterocyclenylaryl, fused cycloalkylheteroaryl, fused cycloalkenylheteroaryl, fused heterocyclenylheteroaryl, fused heterocyclylheteroaryl, aralkyl or heteroaralkyl;
• or R20 and R21 taken together with the nitrogen atom to which R20 and R21 are attached form azaheterocyclyl;
• A3 is a direct bond, alkylene, alkenylene or alkynylene;
• Z1 and Z3 are independently a direct bond, oxygen, sulfur or NH;
• Z2 is a direct bond, oxygen or sulfur;
• B, C, D, and E are independently CH or a heteroatom selected from O, S, N, NOR22 or NR22, or three of B, C, D and E are independently CH or a heteroatom selected from O, S, N or NR22, and the other of B, C, D and E is a direct bond;
• and one of B, C, D and E that are in adjacent positions is other than O and S;
• R22 is hydrogen, alkyl, aryl, lower aralkyl, heteroaryl or lower heteroaralkyl,
• Q1, Q2 and Q3 are independently CH, CX1 or N;
• X1 is halogen;
• and
• n is 0, 1 or 2;
• or
• a prodrug thereof, acid isostere thereof, pharmaceutically acceptable salt thereof, or solvate thereof,
• this process comprising treating a polymeric hydroxamic acid resin compound of formula
• wherein L is absent or a linking group with acid.