Process for the preparation of phenylalanine enamide derivatives

A process for the preparation of a compound of formula (1):

• 13
• wherein:
• Ar1 is an optionally substituted aromatic or heteroaromatic group;
• L2 is a linker group selected from —N(R4)— [where R4 is a hydrogen atom or an optionally substituted straight or branched C1-6alkyl group], —CON(R4)— or —S(O)2N(R4)—;
• R1 is a carboxylic acid (—CO2H) or a derivative or biostere thereof;
• R2 is a hydrogen atom or a C1-6alkyl group;
• Rx, Ry and Rz which may be the same or different is each an atom or group —L1(Alk1)n(R3)v in which L1 is a covalent bond or a linker atom or group, Alk1 is an optionally substituted aliphatic or heteroaliphatic chain, R3 is a hydrogen or halogen atom or group selected from —OR3a [where R3a is a hydrogen atom or an optionally substituted straight or branched C1-6alkyl group or C3-8cycloalkyl group], —SR3a, —CN or an optionally substituted cycloaliphatic, heterocycloaliphatic, polycycloaliphatic, heteropolycycloaliphatic, aromatic or heteroaromatic group, n is zero or the integer 1 and v is the integer 1, 2 or 3 provided that when n is zero and L1 is a covalent bond v is the integer 1;
• or Rz is an atom or group as previously defined and Rx and Ry are joined together to form an optionally substituted spiro linked cycloaliphatic or heterocycloaliphatic group;
• and the salts, solvates, hydrates and N-oxides thereof;
• which comprises reacting a compound of formula (2):
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• wherein:
• Qa is a group —N(R4)H;
• and the salts, solvates, hydrates and N-oxides thereof;
• with a compound Ar1W wherein W is a group selected from X1 (wherein X1 is a leaving atom or group), —COX2 (wherein X2 is a halogen atom or a —OH group) or —SO2X3 (in which X3 is a halogen atom).