Ethyl -fluorobenzoate

Polymorphic forms of I and II of 3- 2-[4-(6-fluorobenzo[r/ isoxazol-3-yl)-3,6-dihydro-2//-pyridin-l-yl]ethyl -2-methyl-6,7,8,9-tetrahydro-4//-pyrido [1,2-n]pyrimidin-4-one was characterized by IR spectroscopy (99MIP1). 

Two polymorphic forms of 3- 2-[4-(6-fluorobenzisoxazol-3-yl)-l,2,3,6-tetrahydropyridin-l-yl]ethyl -2-methyl-6,7,8,9-tetrahydro-4//-pyrido[l,2-n] pyrimidin-4-one (137 R = H) were prepared (99MIP1). Racemic 9-hydroxy-2-methyl-3- 2-[4-(6-fluorobenzo[r/ isoxazol-3-yl)-l,2,3,6-tetrahydro-l-pyridyl] ethyl -6,7,8,9-tetrahydro-4//-pyrido[l, 2-n]pyrimidin-4-one was resolved into its (R)- and (5)-isomers (OOMIPIO). 

A/-[4-[(4-[ F]Fluorobenzylidene)amino-oxy]butyl]maleimide ([ F]FBABM) was synthesised in two steps, involving the preparation of 4-[ F]fluorobenzaldehyde (see Section 4.3.1.1), in an overall radiochemical yield of 35% in 60 min [267], whereas A/-[2-(4-[ F]fluorobenzamido)ethyl]maleimide ([ F]FBEM) was synthesised in three steps via 4-[ F]fluorobenzoic acid (see Section 4.3.1.1) in an overall radiochemical yield of 12% in 150 min [268]. Finally, based on the successful use of nucleophilic /leferoaromatic ort/io-radiofluorination in the pyridine series (see Section 4.3.2.1), 1-[3-(2-p F]fluoropyridin-3-yloxy)propyl]pyrrole-2,5-dione was prepared in 17-20% non-decay-corrected radiochemical yield in a three-step pathway taking less than 110 min [13,269]. These three reagents have been successfully coupled to peptides and proteins (>80% radiochemical yield in 10 min). 

Carbonation of the lithium derivative of 2-methoxybenzo[6]thio-phene affords the corresponding 3-carboxylic acid.183 2-Methylbenzo-[6]thiophene-3-carboxylic acid has been obtained (45%) by carbonation of 2-benzo[6]thienylmethylmagnesium chloride (Section VI,D, 4).528 re-Butyllithium reacts selectively with the bromine atom in 3-bromo-2-fluorobenzo[b]thiophene to give a product, which on carbonation affords 2-fluorobenzo[6]thiophene-3-carboxylic acid.482 Benzo[6]thiophene-7-carboxylic acid is obtained by reduction of the corresponding thioindoxyl with amalgamated zinc and acetic acid.315 Benzo[6]thiophene-3-carboxylic acid and its 2-ethyl derivative have been prepared in high yield by treatment of the pyridinium salt of the 3-chloroacetyl derivative with alkali.132... 

The requisite tricyclic 2,4-diaminoquinazoline precursor (687) was obtained in one step from 5-aminoindole hydrochloride and sodium dicyanamide [282], Subsequent alkylation of (687) with (4-bromome-thyl)benzoic acid yielded (688a). Alkylation of (687) with ethyl (4-bromome-thyl)benzoate afforded (688b), while arylation of (687) with ethyl 4-fluorobenzoate generated the A-aryl analogue (689). 

Amino-4-fluorobenzoic acid (5.41 mmol) dissolved in 15 ml ethyl alcohol was treated with 1.18 ml thionyl chloride, then refluxed overnight, and concentrated. The residue was dissolved in EtOAc, washed with 10% NaOH solution then dried, concentrated, and the product isolated in 82% as a solid. 

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