methyl (2S)-6-amino-2-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoate

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

Procedure: 1.0 g of Boc-Lys(Cbz)-OMe (5) was dissolved in 40 mL MeOH:Ethyl acetate. 100 mg of Palladium on active carbon (Pd/C) was added to the solution. The solution was stirred under hydrogen for 2 hrs. The organic solution was filtered through Celite and washed with 10 mL MeOH. The filtrate was evaporated under reduced pressure to yield Boc-Lys-OMe of formula (6) The organic solution was filtered through Celite washed with 10 mL MeOH The filtrate was evaporated under reduced pressure

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

Procedure: A total amount of Boc-Lys(Cbz)-OMe was dissolved in a mixed solvent of 40 ml of ethyl acetate and 40 ml of methanol, and then the resultant solution was stirred at room temperature for 4 hours under a hydrogen atmosphere while gradually adding 0.223 g of Pd/C. The reaction product was passed through 3.56 g of celite (Sigma Aldrich) to remove Pd/C, and was then washed with 20 ml of methanol (MeOH) two times to obtain a filtrate. The filtrate was evaporated to obtain light viscous solid Boc-Lys-OMe. to remove Pd/C was then washed with 20 ml of methanol (MeOH) two times to obtain a filtrate The filtrate was evaporated

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

Procedure: 1.0 g of Boc-Lys(Cbz)-OMe (5) was dissolved in 40 mL MeOH:Ethyl acetate. 100 mg of Palladium on active carbon (Pd/C) was added to the solution. The solution was stirred under hydrogen for 2 hrs. The organic solution was filtered through Celite and washed with 10 mL MeOH. The filtrate was evaporated under reduced pressure to yield Boc-Lys-OMe of formula (6) The organic solution was filtered through Celite washed with 10 mL MeOH The filtrate was evaporated under reduced pressure

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

Procedure: 1.0 g of Boc-Lys(Cbz)-OMe (5) was dissolved in 40 mL MeOH:Ethyl acetate. 100 mg of Palladium on active carbon (Pd/C) was added to the solution. The solution was stirred under hydrogen for 2 hrs. The organic solution was filtered through Celite and washed with 10 mL MeOH. The filtrate was evaporated under reduced pressure to yield Boc-Lys-OMe of formula (6) The organic solution was filtered through Celite washed with 10 mL MeOH The filtrate was evaporated under reduced pressure

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

Procedure: Following General Procedure A and using N-(3,5-difluorophenylacetyl)-L-alanine (from Example B2 above) and NE-(tert-butoxycarbonyl)-L-lysine methyl ester (Bachem), the title compound was prepared as an oil. The reaction was monitored by tlc (Rf=0.40 in 50% EtOAc/hexanes) and the product was purified by flash chromotography using 50% EtOAc/hexanes as the eluent. the product was purified by flash chromotography

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

Procedure: 1.0 g of Boc-Lys(Cbz)-OMe (5) was dissolved in 40 mL MeOH:Ethyl acetate. 100 mg of Palladium on active carbon (Pd/C) was added to the solution. The solution was stirred under hydrogen for 2 hrs. The organic solution was filtered through Celite and washed with 10 mL MeOH. The filtrate was evaporated under reduced pressure to yield Boc-Lys-OMe of formula (6) The organic solution was filtered through Celite washed with 10 mL MeOH The filtrate was evaporated under reduced pressure

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

Procedure: A 1M stock solution of (S)-methyl 6-amino-2-(tert-butoxycarbonylamino)hexanoate in 20 mL DMF was prepared, and used. A 2 mL aliquot of the (S)-methyl 6-amino-2-(tert-butoxycarbonylamino)hexanoate stock solution, 3-oxocyclobutanecarboxylic acid (2) (Parkway *BX-102, 283 mg), HATU (800 mg), DIEA (1.0 mL) and 8 mL DMF were combined in a 40 mL glass vial, and stirred at ambient temperature overnight. The LC-MS analysis revealed a complete reaction. The reaction mixture was diluted with EtOAc, washed successively with water, sat aq. NaCl, dried over MgSO4, filtered and concentrated under reduced pressure. The crude material was purified by silica gel flash chromatography (hexanes/EtOAc), affording (S)-methyl 2-(tert-butoxycarbonylamino)-6-(3-oxocyclobutanecarboxamido)hexanoate (TU3000-140) as a clear viscous oil. MS (ESI+): calcd. 379.18. found 379.20 (MNa+), calcd. 257.15. found 257.20((M-Boc)H+). H-NMR (400 MHz, DMSO-d6):1.245 (4H, m), 1.371 (9H, s), 1.579 (2H, m), 3.065 (3H, m), 3.135 (4H, m), 3.608 (3H, s), 3.895 (1H, m), 7.209 (1 h, d, J=8.0 Hz), 8.123 (1H, t, J=5.4 Hz). C-NMR (100 MHz, DMSO-d6): 22.850, 27.185, 28.111, 28.551, 30.209, 38.276, 50.859, 51.639, 53.412, 53.529, 78.137, 155.507, 172.992, 173.167, 205.576. a complete reaction washed successively with water dried over MgSO4 filtered concentrated under reduced pressure The crude material was purified by silica gel flash chromatography (hexanes/EtOAc)

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

Procedure: (S)-methyl 6-(benzyloxycarbonylamino)-2-(tert-butoxycarbonylamino)hexanoate (8.60 g) was hydrogenated in 150 mL MeOH over 5% palladium on activated carbon (1.08 g) under 1 atm hydrogen at ambient temperature for 3 hours. The spent catalyst was removed by vacuum filtration through a celite pad which was washed with MeOH. The combined filtrate and wash were concentrated under reduced pressure, affording (S)-methyl 6-amino-2-(tert-butoxycarbonylamino)hexanoate (TU3000-128) as clear viscous oil. MS (ESI+): calcd. 261.17. found 261.20 (MH+). H-NMR (600 MHz, CDCl3):1.328 (2H, m), 1.375 (9H, s), 1.390 (2H, m), 1.55 (1H, m), 1.74(1H, m), 2.623(2H, d, J=6.9 Hz), 3.671 (3H, s), 4.237 (1H, m), 5.007 (1H, m). The spent catalyst was removed by vacuum filtration through a celite pad which was washed with MeOH The combined filtrate and wash were concentrated under reduced pressure

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

Procedure: A total amount of Boc-Lys(Cbz)-OMe was dissolved in a mixed solvent of 40 ml of ethyl acetate and 40 ml of methanol, and then the resultant solution was stirred at room temperature for 4 hours under a hydrogen atmosphere while gradually adding 0.223 g of Pd/C. The reaction product was passed through 3.56 g of celite (Sigma Aldrich) to remove Pd/C, and was then washed with 20 ml of methanol (MeOH) two times to obtain a filtrate. The filtrate was evaporated to obtain light viscous solid Boc-Lys-OMe. to remove Pd/C was then washed with 20 ml of methanol (MeOH) two times to obtain a filtrate The filtrate was evaporated

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

Procedure: 1.0 g of Boc-Lys(Cbz)-OMe (5) was dissolved in 40 mL MeOH:Ethyl acetate. 100 mg of Palladium on active carbon (Pd/C) was added to the solution. The solution was stirred under hydrogen for 2 hrs. The organic solution was filtered through Celite and washed with 10 mL MeOH. The filtrate was evaporated under reduced pressure to yield Boc-Lys-OMe of formula (6) The organic solution was filtered through Celite washed with 10 mL MeOH The filtrate was evaporated under reduced pressure