| 100% |
In tetrahydrofuran; for 12h; |
CBZ-protected Lys (2.5 g, 8.91 mM) was treated with Triphosgene (1.4 g, 4.45 mM) in dry THF at 0 C. The solution was heated to 45 C. for 12 hrs. Any visible precipitates were removed by filtration and the solvent was removed in vacuo. Recrystallization was carried out with Hexane/THF (1:1; v/v) to yield 8. 1H NMR (300 MHz, CDCl3), delta 7.37-7.29 (s, 5H), 5.13 (s, 4H), 4.39-4.3 (d, 2H), 3.6 (s, 2H), 3.23 (s, 2H), 1.9-1.5 (m, 8H) |
| Ca. 80% |
In tetrahydrofuran; at 65℃; for 2h;Inert atmosphere; |
epsilon- (0228) (Z)-L-Lysine and D,L-Valine NCAs were synthesized as per the previous examples, with the inclusion of an additional purification step to remove hydrochloride impurities from the reaction. Dried H-Lys(Z)-OH (2 g, 7.14 mmol) or D,L-Valine (2 g, 17.0 mmol)) were suspended in anhydrous THF (50 ml_) in a three-necked round bottomed flask under argon. Triphosgene (lys: 0.85 g, 2.86 mmol, 1 .2 equiv. phosgene; val: 2.0 g, 6.74 mmol, 1 .2 equiv. phosgene) was then added and the mixture was refluxed at 65 C for 2 h with continuous stirring. After cooling to room temperature, the reaction mixture was sparged with argon for 45 mins into a sat. NaOH solution, then solvent removed completely in vacuo to a white solid. The solid was then suspected in EtOAc (anhydrous), chilled and placed into a separator funnel where the crude NCA solution was gently washed with chilled saturated brine solution (50 ml_), and 0.5 % w/v NaHCOs solution (50 ml_). The organic phase was then dried with MgS04, filtered and concentrated to an oil under low heat, and re-crystalized (x2) from EtOAc (anhydrous) and n-pentane (anhydrous). The resulting crystals were then filtered and washed with n-pentane (dry), then re- precipitated and washed (x 2) with dry n-pentane to afford white powder solids (Yields: -80 %) 1 H NMR (CDCIs): (Z)-L-Lysine NCA 1H NMR (400 MHz, CDCI3): deltaEta 1 .40-1.60 (m, 4H, NH-CH2-CH2-CH2-CH2-), 1 .81 -1.94 (m, 2H, NH-CH2-CH2-CH2-CH2-), 3.18 (m, 2H, NH-CH2-CH2-CH2-CH2-), 4.25 (t, 1 H, C/-/N), 4.97 (s, 1 H, side chain NH), 5.09 (s, 2H, CH2-ArH), 7.04 (s, 1 H, ring NH), 7.3-7.4 (m, 5H, ArH). D,L-Valine NCA 1 H NMR (400 MHz, CDCI3): deltaEta 1 .02 (d, 3H, J= 7.0 Hz, CH3), 1.08 (d, 3H, J= 7.0 Hz, CH3), 2.25 (m, 1 H, CH(CH3)2), 4.22 (d, 1 H, J = 4.4 Hz, CH-NH), 6.95 (s, 1 H, CO-NH). |
| 78% |
In tetrahydrofuran; at 50℃; for 2h;Inert atmosphere; |
Lys(Z)-NCA was synthesized by referring to the literature procedure[30]. Briefly, in a round-bottom flask fitted with a stir bar, L-lysine beta-benzyl ester (1 g, 3.57 mmol) was suspended in anhydrous THF bubbledwith argon flux. After adding 0.5 equiv. of triphosgene, the suspensionwas stirred at 55 C for 2 h. Then, the filtrate of reaction mixture wasconcentrated and crystallized in hexane to achieve the purified Lys(Z)-NCA (yield: 78%). 1H NMR(400 M, DMSO-d6, ppm): 9.09 (s, 1H), 7.32 (m, 5H), 5.00 (s, 2H), 4.41 (m, 1H), 2.99 (m, 2H), 1.69 (m, 2H),1.39-1.29 (m, 4H) |
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
