α v integrin receptor antagonists

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

comprising closing the ring of a compound of formula (II) with heat

wherein R 1 is hydrogen, chlorine, bromine or lower alkyl, P is an amino protecting group and n is 2 or 3, and Y is a group selected from chlorine, bromine, iodine, mesylate, tosylate, brosylate, nosylate or triflate.

2. A process for the preparation of a compound of formula (I)

wherein R 1 is hydrogen, chlorine, bromine or lower alkyl, P is an amino protecting group and n is 2 or 3, comprising

(a) reacting a compound of formula (III)

wherein R 1 and P are as previously defined and R 3 is hydrogen or methyl, with a compound of the formula (IV)

X—(CH 2 ) m —Y   (IV)

wherein Y is a group selected from chlorine, bromine, iodine, mesylate, tosylate, brosylate, nosylate, or triflate, X is a group selected from chlorine, bromine, iodine, mesylate, tosylate, brosylate, nosylate, or triflate, and m is 3 or 4 when R 3 is hydrogen, or m is 2 or 3 when R 3 is methyl, to yield a compound of formula (II)

and

(b) closing the ring of the compound of formula (II) with heat.

3. A process as claimed in claim 1 wherein R 1 is a chlorine atom.

4. A process as claimed in claim 3 wherein Y is a chlorine atom.

5. A process as claimed in claim 4 wherein X is a bromine or iodine atom.

6. A process as claimed in claim 5 wherein the compound of formula (IV) is selected from Cl(CH 2 ) 4 I, Cl(CH 2 ) 3 I, Cl(CH 2 ) 2 I, Cl(CH 2 ) 4 Br, Cl(CH 2 ) 3 Br and Cl(CH 2 ) 2 Br.

7. A process for the preparation of the compounds of the formulae (V) and (VI):

comprising reacting a compound of the formula (VII)

with an alkyllithium to form a reaction mixture, and

reacting the reaction mixture with the compound of the formula (IV)

X—(CH 2 ) m —Y  (IV)

wherein Y is a group selected from chlorine, bromine, iodine, mesylate, tosylate, brosylate, nosylate, and triflate, X is a group selected from chlorine, bromine, iodine, mesylate, tosylate, brosylate, nosylate, or triflate, and m is 3 or 4, to yield a compound of the formula (VIII)

wherein Y is as previously defined, and p is 3 or 4, and

cyclizing the compound of formula VIII, with heat, without isolation, to form the compounds of formulae (V) and (VI).

8. A process as claimed in claim 2 wherein R 1 is a chlorine atom, Y is a chlorine atom, and X is a bromine or iodine atom.

9. A process as claimed in claim 8 wherein the compound of formula (IV) is selected from Cl(CH 2 ) 4 I, Cl(CH 2 ) 3 I, Cl(CH 2 ) 2 I, Cl(CH 2 ) 4 Br, Cl(CH 2 ) 3 Br and Cl(CH 2 ) 2 Br.

10. A process as claimed in claim 2 wherein n is 3 and P is selected from: tert-butylmethoxyphenylsilyl, tert-butoxydiphenylsilyl, trimethylsilyl, triethylsilyl, acetyl, pivaloyl (2,2-dimethyl-1-oxopropyl), o-nitrobenzyloxycarbonyl, p-nitrobenzyloxycarbonyl, benzyloxycarbonyl, tert-butyloxycarbonyl (t-BOC), 2,2,2-trichloroethyloxycarbonyl, benzhydryl, o-nitrobenzyl, p-nitrobenzyl, 2-naphthylmethyl, benzyl, 2,2,2-trichloroethyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, 2-(trimethylsilyl)ethyl, p-methoxybenzyl, p-methoxyphenyl, 4-pyridylmethyl, tert-butyl, allyloxycarbonyl, di-C 1-10 alkylphosphoryl, diarylphosphoryl and di-ar-C 1-10 alkylphosphoryl.