2-methylsulfanylethanamine

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: 1-Ethyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (2-methylsulfanyl-ethyl)-amide (67.0 mg) was prepared by following General Procedure F starting from 1-ethyl-2-(6-trifluoromethyl-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (150.0 mg), 2-methylsulfanyl-ethylamine (45.0 mg), HBTU (200.0 mg) and DIEA (0.2 mL) in DMF (1.0 mL). LCMS: m/z 481; and 1H NMR (DMSO-d6, 400 MHz): δ 8.59 (1H, br. s), 8.26 (1H, br. s), 8.11 (1H, br. s), 7.76-7.68 (2H, m), 7.56 (1H, m), 4.25 (2H, bs. s), 3.51-3.46 (2H, q), 3.32 (2H, s), 2.70-2.66 (2H, t), 2.12 (3H, s), 1.35-1.32 (3H, t).

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

Procedure: 2-(6-Methanesulfonyl-benzothiazol-2-ylamino)-1-methyl-1H-benzimidazole-5-carboxylic acid (2-methylsulfanyl-ethyl)-amide (41 mg) was prepared by following General Procedure F using 2-(6-methanesulfonyl-benzothiazol-2-ylamino)-1-methyl-1H-benzimidazole-5-carboxylic acid (80 mg), 2-methylthio-ethylamine (0.2 ml), HBTU (76 mg), and DIEA (0.2 ml). LCMS: m/z 477.

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

Procedure: 1-Methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzoimidazole-5-carboxylic acid (2-methylsulfanyl-ethyl)-amide (82 mg) was prepared by following General Procedure F using 1-methyl-2-(6-trifluoromethoxy-benzothiazol-2-ylamino)-1H-benzimidazole-5-carboxylic acid (82 mg), 2-methylthio-ethylamine (30 mg), HBTU (76 mg), and DIEA (0.2 ml). LC/MS: m/z 483. 1H NMR (DMSO-d6, 400 MHz): δ 8.58 (s, 1H), 8.09 (s, 1H), 7.91 (m, 1H), 7.47 (m, 2H), 7.48 (d, 1H), 7.37 (d, 1H), 3.64 (s, 3H), 3.48 (q, 2H), 2.68 (t, 2H), and 2.12 (s, 3H), —NH proton signal was not observed.

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

Conditions: temp:220.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-chloro-3-nitrotoluene (1.3 g, 7.3 mmol), 2-(methylthio)ethylamine (1.4 mL, 15 mmol) and N,N-diisopropylethylamine (5.0 mL, 29 mmol) in 1-methyl-2-pyrrolidinone (3.7 mL) was heated to 220° C. by microwave for 1 h. The mixture was diluted with ethyl acetate (0.10 L) and washed with water (50 mL×2), brine (50 mL), dried over sodium sulfate, filtered and concentrated to give a crude material. The another batch starting from 1.3 g of 2-chloro-3-nitrotoluene was combined to this crude material and the combined crude products were purified by column chromatography on silica gel eluting with hexane/ethyl acetate (3/1) to afford 2.6 g (77%) of the title compound. washed with water (50 mL×2), brine (50 mL) dried over sodium sulfate filtered concentrated to give a crude material the combined crude products were purified by column chromatography on silica gel eluting with hexane/ethyl acetate (3/1)

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

Procedure: Replicate the preparation of the ligand used in Ex. 7 except use 0.928 g (9.758 mmol) of the pyrrole-2-carbaldehyde and 0.999 mL (10.734 mmol, ρ=0.980 gcm−3) of 2-(methylthio)ethylamine instead of N1,N1-dimethylethane-1,2-diamine to give 1.62 g (98%) of N-((1H-pyrrol-2-yl)methylene)-2-(methylthio)ethanamine as a pale yellow oil, which is analytically pure by GC-MS & 1H-NMR: 1H NMR (400 MHz, CDCl3) δ 9.45 (s, br, 1H), 7.99 (s, 1H), 6.78 (s, 1H), 6.40 (d, J=1.9 Hz, 1H), 6.14 (s, 1H), 3.64 (t, J=6.9 Hz, 2H), 2.66 (t, J=6.9 Hz, 2H), 2.04 (s, 3H). the preparation of the ligand

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

Procedure: Using a procedure similar to that described in Example 1, except using 5-[5-(3,5-bistrifluoromethylphenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl]-imidazo[1,2-a]pyridine-8-carboxylic acid (45 mg) and 2-methylthioethylamine (0.016 mL), the title compound was isolated as an orange-reddish solid (11.9 mg, 23%). MS (ES): M/Z [M+H]=585. 1H NMR (400 MHz, CHLOROFORM-d): 2.22 (s, 3H), 2.85 (t, J=6.8 Hz, 2H), 3.82 (q, J=6.6 Hz, 2H), 4.01 (d, J=17.0 Hz, 1H), 4.44 (d, J=16.8 Hz, 1H), 7.21 (d, J=7.6 Hz, 1H), 7.85 (s, 1H), 8.02 (s, 1H), 8.12 (s, 2H), 8.28 (d, J=7.6 Hz, 1H), 8.90 (d, J=1.0 Hz, 1H), 10.67 (br. s., 1H). 19F NMR (376 MHz, CHLOROFORM-d): −80.0 (s, 3F), −63.3 (s, 6F).

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

Procedure: Using a procedure similar to that described in Example 1, except using 5-[5-(3,5-bistrifluoromethylphenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl]-imidazo[1,2-a]pyridine-8-carboxylic acid (45 mg) and 2-methylthioethylamine (0.016 mL), the title compound was isolated as an orange-reddish solid (11.9 mg, 23%). MS (ES): M/Z [M+H]=585. 1H NMR (400 MHz, CHLOROFORM-d): 2.22 (s, 3H), 2.85 (t, J=6.8 Hz, 2H), 3.82 (q, J=6.6 Hz, 2H), 4.01 (d, J=17.0 Hz, 1H), 4.44 (d, J=16.8 Hz, 1H), 7.21 (d, J=7.6 Hz, 1H), 7.85 (s, 1H), 8.02 (s, 1H), 8.12 (s, 2H), 8.28 (d, J=7.6 Hz, 1H), 8.90 (d, J=1.0 Hz, 1H), 10.67 (br. s., 1H). 19F NMR (376 MHz, CHLOROFORM-d): −80.0 (s, 3F), −63.3 (s, 6F).

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

Procedure: Using a procedure similar to that described in Example 1, except using 5-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl]-indolizine-8-carboxylic acid (37 mg, described above in Example 3) and 2-methylthioethylamine, the title compound was isolated as an orange-reddish solid (21.2 mg, 49%). MS (ES): M/Z [M+H]=516. 1H NMR (400 MHz, CHLOROFORM-d): 2.17 (s, 3H), 2.83 (t, J=6.2 Hz, 2H), 3.75 (q, J=6.0 Hz, 2H), 3.91 (d, J=16.6 Hz, 1H), 4.28 (d, J=16.6 Hz, 1H), 6.83 (d, J=7.4 Hz, 1H), 7.02-7.08 (m, 1H), 7.17 (d, J=7.2 Hz, 1H), 7.46 (t, J=1.7 Hz, 1H), 7.55 (s, 2H), 8.73 (d, J=1.6 Hz, 1H). 19F NMR (376 MHz, CHLOROFORM-d): −79.8 (s, 3F).