(2,6-difluorophenyl)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:

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 (2,6-difluorophenyl)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 (2,6-difluorophenyl)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 (2,6-difluorophenyl)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 is prepared from (R)-6-fluoro-3-(4-oxiranylmethoxy-phenyl)-benzo[d]isoxazole, 2,6-difluorobenzylamine, and ethanol essentially as described above in Example 112. Purity by LC/MS=96%, [M+H]+=429.

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

Procedure: The title compound is prepared from a mixture of 2-(4-benzo[b]thiophen-3-yl-phenoxymethyl)-oxirane, 2,6-difluorobenzylamine and ethanol essentially as described above in Example 94. Purity by LC/MS=99%, [M+H]+=426.

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

Procedure: The title compound is prepared from a mixture of 2-(4-benzo[b]thiophen-3-yl-phenoxymethyl)-oxirane, 2,6-difluorobenzylamine and ethanol essentially as described above in Example 94. Purity by LC/MS=99%, [M+H]+=426.

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

Procedure: To N1-(3-chlorophenyl)-2-chloroacetamide (61 mg) in DMF (1 mL) was added 2,6-difluorobenzylamine (38 mg) and triethylamine (0.1 mL) and 4-chlorobenzoyl chloride (58 mg) the reaction mixture was stirred at room temperature for 15 min and then purified by HPLC preparative to yield the title compound (55 mg). MS (m/e): 447.0 (M−H). Procedure E purified by HPLC preparative

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

Procedure: To N1-(3-chlorophenyl)-2-chloroacetamide (61 mg) in DMF (1 mL) was added 2,6-difluorobenzylamine (38 mg) and triethylamine (0.1 mL) and 4-chlorobenzoyl chloride (58 mg) the reaction mixture was stirred at room temperature for 15 min and then purified by HPLC preparative to yield the title compound (55 mg). MS (m/e): 447.0 (M−H). Procedure E purified by HPLC preparative

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Crude 2-methyl-3-[(2R)-Boc-amino-2-phenylethoxy]-4H-pyran-4-one (1.00 g, ˜2.90 mmol), 2,6-difluorobenzyl amine (700 μL, 5.8 mmol) and ethanol (3 mL) were combined and heated to 120° C. in a pressure vessel. After 16 h, the volatiles were removed in vacuo and the residue purified by column chromatography, eluting with EtOAc. The product was isolated as a white foam (204 mg, 0.43 mmol, 15%, assuming pure starting material). 1H NMR (CDCl3-300 MHz) δ 7.42-7.19 (m, 7H); 6.98 (t, J=8.1 Hz, 2H); 6.43 (d, J=7.8 Hz, 1H); 5.06 (s, 2H); 4.87-4.83 (m, 1H); 4.06 (dd, J1=9.9 Hz, J2=4.2 Hz, 1H); 3.93 (dd, J=9.9 Hz, J2=6.8 Hz, 1H); 2.34 (s, 3H); 1.42 (s, 9H); LRMS m/z 471.1 (M++1), 371.0 (M+−boc+1). the volatiles were removed in vacuo the residue purified by column chromatography eluting with EtOAc The product was isolated as a white foam (204 mg, 0.43 mmol, 15%, assuming pure starting material)