N,N,2,2-tetramethylpyrrolidin-3-amine

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: To a solution of racemic N,N,2,2-tetramethyl-3-pyrrolidinamine (0.1466 g, 1.031 mmol) in DMF (6 mL) was added N,N-diisopropylethylamine (0.220 mL, 1.263 mmol) and tris(1,1-dimethylethyl)2-(2,6-dichloro-5-fluoro-4-pyrimidinyl)-1,1,2-hydrazinetricarboxylate (0.513 g, 1.031 mmol), and the solution was stirred overnight. The solution was partitioned between Et2O (100 mL) and water (20 mL), and the organic phase was washed with a fresh portion of water (20 mL). The combined aqueous phase was extracted with a fresh portion of Et2O (50 mL), and the combined organic phase was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The residue was purified by gradient silica gel chromatography (0% to 100% EtOAc in hexanes) to give racemic tris(1,1-dimethylethyl)2-{2-chloro-6-[3-(dimethylamino)-2,2-dimethyl-1-pyrrolidinyl]-5-fluoro-4-pyrimidinyl}-1,1,2-hydrazinetricarboxylate (0.4647 g, 75% yield) as a white foam. LCMS: (M+H)+: 603.3. The solution was partitioned between Et2O (100 mL) and water (20 mL) the organic phase was washed with a fresh portion of water (20 mL) The combined aqueous phase was extracted with a fresh portion of Et2O (50 mL) the combined organic phase was dried over anhydrous Na2SO4 filtered concentrated in vacuo The residue was purified by gradient silica gel chromatography (0% to 100% EtOAc in hexanes)

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

Procedure: To a solution of racemic N,N,2,2-tetramethyl-1-(phenylmethyl)-3-pyrrolidinamine (0.5637 g, 2.426 mmol) in MeOH (24 mL) was added 1 N aq. HCl (4.9 ml) and 10% Pd/C (50% water, 113 mg). The mixture was hydrogenated overnight, and then filtered through a 0.2 μM membrane. The resulting solution was concentrated in vacuo. The residue was diluted with 1 N aq. NaOH (20 mL) and extracted with DCM (2×100 mL). The combined organic phase was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to afford crude, racemic N,N,2,2-tetramethyl-3-pyrrolidinamine (0.2930 g, 85% yield) as a pale yellow oil. LCMS: (M+H)+: 143.1. filtered through a 0.2 μM membrane The resulting solution was concentrated in vacuo The residue was diluted with 1 N aq. NaOH (20 mL) extracted with DCM (2×100 mL) The combined organic phase was dried over anhydrous Na2SO4 filtered concentrated in vacuo