(1S)-N-methyl-1-phenyl-2-pyrrolidin-1-ylethanamine

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

Procedure: Compound 13a was prepared by following the procedure of Example 1, Step f, except 12a was substituted for 6a, 1-[2-methylamino-2-(S)-phenyl-ethyl]-pyrrolidin-3-(S)-ol dihydrochloride was substituted for methyl-[1-(S)-phenyl-2-pyrrolidin-1-yl-ethyl]-amine and diisopropylethylamine (3.3 eq) was substituted for diisopropylethylamine (2.2 eq). The resulting oil was dissolved in dichloromethane (0.1 M) and a solution of hydrochloric acid (5.5 eq) in ether (2.0 M) was added slowly at 0° C. The solvent was removed under reduced pressure. The resulting solid was triturated with ether then filtered off to afford the product as the hydrochloric acid salt. (55%) 1H NMR (400 MHz, DMSO-d6) δ 10.22-10.72 (m, 1H), 7.55 (m, 1H), 7.18-7.42 (m, 9H), 6.17 (m, 1H), 5.42-5.62 (m, 1H), 4.44 (m, 1H), 4.13 (m, 3H), 3.84 (m, 2H), 3.40-3.72 (m, 3H), 3.17 (m, 1H), 2.83 (s, 3H), 2.76 (m, 3H), 2.09-2.35 (m, 1H), 1.89 (m, 1H). Mass Spectral Analysis m/z=446.4 (M+H)+ tR=3.45 min (98%) Compound 13a was prepared The solvent was removed under reduced pressure The resulting solid was triturated with ether then filtered off

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

Procedure: To a stirring solution of methyl-[1-(S)-phenyl-2-pyrrolidin-1-yl-ethyl]-amine in acetonitrile (0.3 M) at 0° C. under nitrogen was added diisopropylethylamine (2.2 eq), 6a (1.1 eq) and O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate (TBTU) (1.1 eq). The reaction was stirred at room temperature overnight. The acetonitrile was removed under reduced pressure. The remaining oil was partitioned between ethyl acetate and saturated sodium bicarbonate. The phases were separated and the organic phase was washed with saturated sodium bicarbonate (2×), brine (1×), dried over sodium sulfate, filtered, concentrated in vacuo and purified by flash chromatography using the ISCO (1-15% gradient methanol/dichloromethane) to afford the product. (65%) 1H NMR (400 MHz, CDCl3) δ 7.29 (m, 9H), 6.21 (m, 1H), 5.62 (m, 1H), 4.31 (m, 2H), 3.95 (m, 1H), 3.71 (m, 1H), 3.05 (m, 1H), 2.82 (m, 5H), 2.55 (m, 2H), 1.85 (m, 5H), 1.46 (s, 9H). Mass Spectral Analysis m/z=452.3 (M+H)+ tR=4.92 min (96%) The acetonitrile was removed under reduced pressure The remaining oil was partitioned between ethyl acetate and saturated sodium bicarbonate The phases were separated the organic phase was washed with saturated sodium bicarbonate (2×), brine (1×) dried over sodium sulfate filtered concentrated in vacuo purified by flash chromatography to afford the product