N-(TERT-BUTOXYCARBONYL)-L-SERINE BETA-LACTONE

White powder

Standard Procedure for the Synthesis of Boc-Imidazol-1-yl-Ala (AA2); Step 2-1. Boc-Serine-β-lactone (AA2-1).; This procedure is based on that found in the literature (Vederas, J. C.; et al. J. Am. Chem. Soc. 1987, 109, 4649-4659). Into a dry 250 mL 3-neck flask equipped with a mechanical stirrer under a nitrogen atmosphere was added triphenylphosphine (4.5 g, 17.1 mmol, 1.1 eq), followed by 100 mL of an anhydrous THF:CHAnhydrous tetrahydrofuran (THF) (100 mL) was added dropwise to triphenylphosphine (Ph3P) (6.3 g, 24.00 mmol), stirred at -78 ° C under argon for more than 10 min. A solution of diethyl azodicarboxylate (DEAD) was added dropwise and the resulting solution was stirred for 10 min. The above tetrahydrofuran mixed solution was added dropwise to a solution of N- (tert-butoxycarbonyl 1) -L-serine (5 g, 24.36 mmol) and stirred for more than 20 min. The resulting solution was stirred at -78 ° C for 20 min and then further stirred at room temperature for 2.5 h. The solvent was removed from tetrahydrofuran and the crude product was purified by chromatography on a column (3: 1 by volume ethane / ethyl acetate). And finally purified by recrystallization from ethyl acetate / n-hexane to give white solid compound 2 (2.4 g, yield 53percent).To a suspension containing 2.05 g (12.1 mmol) of 2-amino-6-chloropurine in 5 mL of DMSO was added 1.50 mL (1.56 g, 10.2 mmol) of DBU over a period of 15 min. Within 15 min, a solution containing 1.74 g (9.30 mol) of N-(tert-butoxycarbonyl)-L-serine beta-lactone dissolved in 5 mL of DMSO was added dropwise and the reaction mixture was stirred for additional 3 h. The reaction was stopped by adding HOAc (585 muL, 10.2 mmol) and the solvent was removed under diminished pressure. Purification of the crude product was done by flash chromatography on a silica gel column (10 * 2 cm) using a gradient of 9:1 EtOAc/MeOH to 9:1:0.05 EtOAc/MeOH/HOAc. After co-evaporation with portions of toluene, the product was obtained as a white solid: yield 2.60 g (80%); Rf 0.40 (9:1:0.05 EtOAc/MeOH/HOAc); 1H NMR (DMSO-d6) delta 1.24 (s, 9H), 4.15-4.45 (m, 3H), 6.69 (s, 1H), 6.89 (s, 2H), 7.89 (s, 1H) and 8.04 (s, 1H); 13C NMR (DMSO-d6) delta 27.9, 43.6, 52.6, 78.3, 123.2, 143.3, 149.1, 154.1, 155.1, 159.7 and 171.2; mass spectrum (APCI), m/z 357.1083 (M+H)+ (C13H18N6O4Cl requires m/z 357.1078).2-amino-6-chloropurine (Compound 5) was added to diazabicyclo (DBU) (0.43 g, 2.85 mmol) (10.55 g, 3.35 mmol) in dimethylformamide (DMF) (10 mL). After 15 min compound 2 (0.5 g, 2.6 mmol) was added to the above dimethylformamide solution and stirred at room temperature for 3 h. The solvent was removed under vacuum and purified by silica gel column chromatography (eluent: EtOAc / MeOH / AcOH = 9: 1: 0.1) to afford white solid product 3 (0.58 g, 63% yield).

An important -lactone inhibitor

Molecular Weight:187.19
XLogP3:0.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:3
Exact Mass:187.08445790
Monoisotopic Mass:187.08445790
Topological Polar Surface Area:64.6
Heavy Atom Count:13
Complexity:231
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes