(2,5-dichlorophenyl)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 from 3-[2-(2-pyridyl)ethylamino]-6-methyl-1-carboxymethylpyrazinone and 2,5-dichlorobenzylamine using the procedure of EXAMPLE V, Step F, mp 188°-191° C.: MS (FAB) 446 (M+1)+.

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

Procedure: The title compound was prepared using the procedure described in Example 222B using 2,5-dichlorobenzylamine and 2-(5-isoquinolinyl)propanoic acid instead of 4-(trifluoromethoxy)benzylamine and 5-isoquinolinylacetic acid. MS (ESI+) m/z 359 (M+H)+; MS (ESI−) m/z 357 (M−H)−; 1H NMR (DMSO, 300 MHz) δ 1.54 (d, J 7.1, 3H), 4.20 (m, 2H), 4.53 (q, J 7.1, 1H), 7.06 (s, 1H), 7.32 (d, J 8.4, 1H), 7.44 (d, J 8.4, 1H), 7.51 (s, 1H), 7.78 (t, J 7.8, 1H), 7.90 (d, J 6.5, 1H), 8.16 (d, J 8.1, 1H), 8.26 (d, J 6.4, 1H), 8.60 (d, J 6.2, 1H), 8.65 (t, J 5.8, 1H), 9.49 (s, 1H).

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

Procedure: The title compound was prepared using the procedure described in Example 222B using 2,5-dichlorobenzylamine and 2-(5-isoquinolinyl)propanoic acid instead of 4-(trifluoromethoxy)benzylamine and 5-isoquinolinylacetic acid. MS (ESI+) m/z 359 (M+H)+; MS (ESI−) m/z 357 (M−H)−; 1H NMR (DMSO, 300 MHz) δ 1.54 (d, J 7.1, 3H), 4.20 (m, 2H), 4.53 (q, J 7.1, 1H), 7.06 (s, 1H), 7.32 (d, J 8.4, 1H), 7.44 (d, J 8.4, 1H), 7.51 (s, 1H), 7.78 (t, J 7.8, 1H), 7.90 (d, J 6.5, 1H), 8.16 (d, J 8.1, 1H), 8.26 (d, J 6.4, 1H), 8.60 (d, J 6.2, 1H), 8.65 (t, J 5.8, 1H), 9.49 (s, 1H).

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

Procedure: The title compound was prepared from 3-[2-(2-pyridyl)ethylamino]-6-methyl-1-carboxymethylpyrazinone and 2,5-dichlorobenzylamine using the procedure of EXAMPLE V, Step F, mp 188°-191° C.: MS (FAB) 446 (M+1)+.

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

Procedure: The title compound was prepared from 3-[2-(2-pyridyl)ethylamino]-6-methyl-1-carboxymethylpyrazinone and 2,5-dichlorobenzylamine using the procedure of EXAMPLE V, Step F, mp 188°-191° C.: MS (FAB) 446 (M+1)+.

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 using the procedure described in Example 222B using 2,5-dichlorobenzylamine and 2-(5-isoquinolinyl)propanoic acid instead of 4-(trifluoromethoxy)benzylamine and 5-isoquinolinylacetic acid. MS (ESI+) m/z 359 (M+H)+; MS (ESI−) m/z 357 (M−H)−; 1H NMR (DMSO, 300 MHz) δ 1.54 (d, J 7.1, 3H), 4.20 (m, 2H), 4.53 (q, J 7.1, 1H), 7.06 (s, 1H), 7.32 (d, J 8.4, 1H), 7.44 (d, J 8.4, 1H), 7.51 (s, 1H), 7.78 (t, J 7.8, 1H), 7.90 (d, J 6.5, 1H), 8.16 (d, J 8.1, 1H), 8.26 (d, J 6.4, 1H), 8.60 (d, J 6.2, 1H), 8.65 (t, J 5.8, 1H), 9.49 (s, 1H).

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

Procedure: Tetrahydrofuran (13 mL), 3-butoxy-4-(1,1-dimethyl-propylamino)-cyclobut-3-ene-1,2-dione (1,20 g, 5 mmol) and 2,5-dichlorobenzylamine (0.88 g, 5 mmol) were stirred together for approximately 64.5 hours. Removal of solvent and thorough trituration of the residue with diethyl ether gave 1.51 g of a light yellow solid. As purification of this material by three recrystallizations from acetonitrile was unrewarding, the recovered crude product was subjected to HPLC. The solid isolated from the appropriate fractions was recrystallized from acetonitrile to afford 0.598 g of the title compound as a white solid: mp 195°-196° C. MS (m/z) 340/342/344 (M+). HPLC indicates a major component (>99%). Removal of solvent and thorough trituration of the residue with diethyl ether

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

Procedure: Employing the procedure of Example 2, Step 4, and a reaction period of 23 hours, 2,5-dichlorobenzylamine (0.88 g, 5 mmol) and 3-butoxy-4-tert-butylamino-cyclobut-3-ene-1,2-dione (1. 13 g, 5 mmol) in tetrahydrofuran (15 mL ) were converted to 1.52 g of a cream-colored solid. Recrystallization of this material from acetonitrile (twice) and from methanol provided 0.853 g of the tide compound as a white solid: mp 236° C. (softens 216° C.). MS (m/z) 326/328/330 (M+). Recrystallization of this material from acetonitrile (twice) and from methanol

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

Procedure: A solution of methyl dimethoxyacetate (0.823 g, 6.08 mmol) and 2,5-dichlorobenzylamine (1.0 g, 5.7 mmol) was heated to 90° C. in a sealed tube for 48 h. The crude material was purified by column chromatography on silica gel [eluting with 40% EtOAc in hexanes] to afford the title compound as a clear oil. 1H NMR (400 MHz, CDCl3) δ=3.41 (s, 6H), 4.53 (d, J=6.6 Hz, 2H), 4.75 (s, 1H), 7.19-7.23 (m, 1H), 7.30 (d, J=8.4 Hz, 1H), 7.35 (d, J=2.5 Hz, 1H). MS (ES+): m/z=278/280/282 [MH+]. HPLC: tR=3.03 min (ZQ2, polar—5 min). The crude material was purified by column chromatography on silica gel [eluting with 40% EtOAc in hexanes]