(2-chloro-6-fluorophenyl)methanamine

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared by essentially following the same procedures described for Intermediate XLIV, using (2-chloro-6-fluorophenyl)methanamine and 2-bromoimidazo[2,1-b]thiazole-6-carboxylic acid as starting materials.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared by essentially following the same procedures described for Intermediate XLIV, using (2-chloro-6-fluorophenyl)methanamine and 2-bromoimidazo[2,1-b]thiazole-6-carboxylic acid as starting materials.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared by essentially following the same procedures described for Intermediate I, using (2-chloro-6-fluorophenyl)methanamine and ethyl 6-bromoimidazo[1,2-a]pyridine-2-carboxylate as starting materials.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared by essentially following the same procedures described for Intermediate I, using (2-chloro-6-fluorophenyl)methanamine and ethyl 6-bromoimidazo[1,2-a]pyridine-2-carboxylate as starting materials.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3-{3-[(2R)-2-({(2R)-2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl}amino)propyl]phenyl}propanoic acid (Preparation 60) (150 mg, 0.29 mmol), O-(1H-benzotrizol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (133 mg, 0.35 mmol), 2-fluoro-6-chlorobenzylamine (56 mg, 0.35 mmol) and triethylamine (0.12 ml, 0.88 mmol) were stirred at room temperature for 16 hours in N,N-dimethylformamide (3 ml). The solvent was removed in vacuo and the resulting brown oil was purified by flash column chromatography on silica gel eluting with dichloromethane:methanol:880 ammonia (98:2:0.2 followed by 94:6:0.6 by volume) to give the title compound as a white foam (30 mg). The solvent was removed in vacuo the resulting brown oil was purified by flash column chromatography on silica gel eluting with dichloromethane

Conditions: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A flask was charged with 1.54 g. (0.01 mole) of 7-amino[ 1,2,5]thiadiazolo[3,4-d]pyrimidine prepared by the process set forth in Example 1 and 4.0 g. (0.025 mole) of 2-chloro-6-fluorobenzylamine prepared by the process set forth in Example 2. The suspension was stirred and heated at 105° C. for 18 hours. Ten ml. water and 20 ml. hexane were added in one portion and the resulting solid collected by filtration. The cake was washed with hexane and dried at 50° C. in vacuo to afford 2.86 g. (97%) of product. M.p. 224°-226° C.; tlc on silica gel in chloroform-methanol (8:1) showed a single fluorescent blue spot at Rf = 0.8; NMR (DMSO-d6) δ 4.92 (2H, s); 7.21 (broad s, 3H); 8.44 (s, 1H); 9.45 (s, 1H). A flask was charged with 1.54 g the resulting solid collected by filtration The cake was washed with hexane dried at 50° C. in vacuo to afford 2.86 g

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: An autoclave was charged with 89.0 g. (0.5 mole) of 2-chloro-6-fluorobenzyl chloride, 170.0 g. (10 mole) ammonia and 50 ml. benzene. The reaction vessel was sealed and the contents heated at 100° C. for 15 hours. The excess ammonia was carefully evaporated off from the cooled contents of the autoclave with a stream of nitrogen. The residue was washed with water, and the organic phase after drying with anhydrous MgSO4, fractionated to afford 72.4 g. (90%) of product as a clear liquid; b.p. 99°-100° C./20 mm; NMR (CDCl3) δ 1.46 (s, 2H); 3.88 (d, 2H); 7.00 (m, 3H). An autoclave was charged with 89.0 g The reaction vessel was sealed The excess ammonia was carefully evaporated off from the cooled contents of the autoclave with a stream of nitrogen The residue was washed with water the organic phase after drying with anhydrous MgSO4 to afford 72.4 g

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: An autoclave was charged with 89.0 g. (0.5 mole) of 2-chloro-6-fluorobenzyl chloride, 170.0 g. (10 mole) ammonia and 50 ml. benzene. The reaction vessel was sealed and the contents heated at 100° C. for 15 hours. The excess ammonia was carefully evaporated off from the cooled contents of the autoclave with a stream of nitrogen. The residue was washed with water, and the organic phase after drying with anhydrous MgSO4, fractionated to afford 72.4 g. (90%) of product as a clear liquid; b.p. 99°-100° C./20 mm; NMR (CDCl3) δ 1.46 (s, 2H); 3.88 (d, 2H); 7.00 (m, 3H). An autoclave was charged with 89.0 g The reaction vessel was sealed The excess ammonia was carefully evaporated off from the cooled contents of the autoclave with a stream of nitrogen The residue was washed with water the organic phase after drying with anhydrous MgSO4 to afford 72.4 g

Conditions: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A flask was charged with 1.54 g. (0.01 mole) of 7-amino[1,2,5]thiadiazolo[3,4-d]pyrimidine prepared by the process set forth in Example 1 and 4.0 g. (0.025 mole) of 2-chloro-6-fluorobenzylamine prepared by the process set forth in Example 2. The suspension was stirred and heated at 105° C. for 18 hours. Ten ml. water and 20 ml. hexane were added in one portion and the resulting solid collected by filtration. The cake was washed with hexane and dried at 50° C. in vacuo to afford 2.86 g. (97%) of product. M.p. 224°-226° C.; tlc on silica gel in chloroform-methanol (8:1) showed a single fluorescent blue spot at Rf =0.8; NMR (DMSO-d6) δ 4.92 (2H, s); 7.21 (broad s, 3H); 8.44 (s, 1H); 9.45 (s, 1H). A flask was charged with 1.54 g the resulting solid collected by filtration The cake was washed with hexane dried at 50° C. in vacuo to afford 2.86 g

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: An autoclave was charged with 89.0 g. (0.5 mole) of 2-chloro-6-fluorobenzyl chloride, 170.0 g. (10 mole) ammonia and 50 ml. benzene. The reaction vessel was sealed and the contents heated at 100° C. for 15 hours. The excess ammonia was carefully evaporated off from the cooled contents of the autoclave with a stream of nitrogen. The residue was washed with water, and the organic phase after drying with anhydrous MgSO4, fractionated to afford 72.4 g. (90%) of product as a clear liquid; b.p. 99°-100° C./20 mm; NMR (CDCl3) δ 1.46 (s, 2H); 3.88 (d, 2H); 7.00 (m, 3H). An autoclave was charged with 89.0 g The reaction vessel was sealed The excess ammonia was carefully evaporated off from the cooled contents of the autoclave with a stream of nitrogen The residue was washed with water the organic phase after drying with anhydrous MgSO4 to afford 72.4 g