BOC-N-ETHYL GLYCINE

White powder

Following the general procedure of Grigg [Blaney, P.; Grigg, R.; Rankovic, Z.; Thornton- Pett, M.; Xu, J. Tetrahedron, 2002, 58, 1719-1737] a roundbottom flask was charged with sodium hydride (480mg 60percent dispersion in oil, 12.0 mmol, 4.0 equiv) and purged with nitrogen for 15 min. THF (6.OmL) was added to the flask, and the suspension was cooled to 0 Following the general procedure of Grigg [Blaney, P.; Grigg, R.; Rankovic, Z.; Thornton-Pett, M.; Xu, J. Tetrahedron, 2002, 58, 1719-1737] a roundbottom flask was charged with sodium hydride (480mg 60percent dispersion in oil, 12.0 mmol, 4.0 equiv) and purged with nitrogen for 15 Example 10 N-Boc-N-methyl-L-glycine; Following the general procedure of Grigg [Blaney, P.; Grigg, R.; Rankovic, Z.; Thornton-Pert, M.; Xu, J. Tetrahedron, 2002, 55, 1719-1737] a roundbottom flask was charged with sodium hydride (480mg 60percent dispersion in oil, 12.0 mmol, 4.0 equiv) and purged with nitrogen for 15 min. THF (6.OmL) was added to the flask, and the suspension was cooled to 0 Example 29a b c Following the general procedure of Grigg [Blaney, P.; Grigg, R.; Rankovic, Z.; Thornton-Pett, M.; Xu, J. Tetrahedron, 2002, 58, 1719-1737] a roundbottom flask was charged with sodium hydride (480mg 60percent dispersion in oil, 12.0 mmol, 4.0 equiv) and purged with nitrogen for 15 min. THF (6.OmL) was added to the flask, and the suspension was cooled to 0 2-[(tert-butoxy)-N-ethylcarbonylamino]acetic Acid A solution of di-tert-butyl dicarbonate (2.18 g, 12.5 mmol) in dimethoxyethane (30 mL) was added to a stirred solution of 2-(ethylamino)acetic acid in NaA solution of di-tert-butyl dicarbonate (2.18 g, 12.5 mmol) in dimethoxyethane (30 mL) was added to a stirred solution of 2-(ethylamino)acetic acid in NaGeneral procedure: A suspension of NaH in mineral oil (40 mmol) was added to a stirred solution of NExample 10 2-[(tert-butoxy)-N-ethylcarbonylamino]acetic Acid A solution of di-tert-butyl dicarbonate (2.18 g, 12.5 mmol) in dimethoxyethane (30 mL) was added to a stirred solution of 2-(ethylamino)acetic acid in Na2CO3 (1.04 g, 10 mmol in water, 30 mL). Stirring was continued for 4 h, then the reaction mixture was acidified with hydrochloric acid (1 N, 30 mL) and extracted with ethyl acetate (3×30 mL). The organic layers were dried over Na2SO4 and concentrated in vacuo to give 2-[(tert-butoxy)-N-ethylcarbonylamino]acetic acid as a colorless oil with quantitative yield. 1H NMR (CDCl3), delta 3.95 (m, 2H), 3.30 (m, 2H), 1.45 (m, 9H), 1.12 (t, J=7.2 Hz, 3H).A solution of di-tert-butyl dicarbonate (2.18 g, 12.5 mmol) in dimethoxyethane (30 mL) was added to a stirred solution of 2-(ethylamino)acetic acid in Na2CO3 (1.04 g, 10 mmol in water, 30 mL). Stirring was continued for 4 h, then the reaction mixture was acidified with hydrochloric acid (1 N, 30 mL) and extracted with ethyl acetate (3×30 mL). The organic layers were dried over Na2SO4 and concentrated in vacuo to give 2-[(tert-butoxy)-N-ethylcarbonylamino]acetic acid as a colorless oil in quantitative yield. 1H NMR (CDCl3), delta 3.95 (m, 2H), 3.30 (m, 2H), 1.45 (m, 9H), 1.12 (t, J=7.2 Hz, 3H).Example 8 N-Boc-N-methyl-L-alanine-L-dehydropyranylglycine A mixture of N-Cbz-dehydropyranylglycine methyl ester a (Burk, M. J.; Gross, M. F.; Martinez, J. P. J. Am. Chem. Soc. 1995, 117, 9375, and references therein) (5.2 g, 17 mmol), 5% Pd.C (500 mg), MeOH (75 mL) and THF (25 mL) was maintained under an atmosphere of H2 for 24 h. The mixture was filtered through Celite and the Celite washed with MeOH, and concentrated under reduced pressure to afford a quantitative yield of amine b as a colorless oil, which was carried on directly.N-Boc-protected cyclic sulfonyl amino acid Sulfide a (810 mg, 2.5 mmol), synthesised according to the general procedure of Shieh [Shieh, W-C.; Xue, S.; Reel, N.; Wu, R.; Fitt, J.; Repic, O. Tetrahedron: Asymmetry, 2001, 12, 2421-2425], was dissolved in methanol (25 mL). Oxone (4.5 g) was dissolved in deionized water (25 mL). The methanol solution of substrate was cooled to -10 C., and the aqueous solution of ozone was added to the reaction slowly. The reaction was kept on ice and gradually allowed to warm to room temperature while stirring overnight. Deionized water was used to dilute the reaction to approximately 150 mL, then poured into 90% ethyl acetate-hexanes for extraction. The organic phase was dried (Na2SO4), adsorbed onto Celite and purified by chromatography ISCO CombiFlash 40 g column, 5-90% ethyl acetate-hexanes over 30 min to afford 804 mg (2.27 mmol, 91%) of the product sulfone b.Example 26 FMOC-Protected dimethylpenicillamine P3-P4 intermediate To a stirred solution of (R)-2-amino-3-mercapto-3-methylbutanoic acid a (500 mg, 3.35 mmol) in 13.1 mL 0.5 N NaOMe in MeOH was added CH3I (784 mg, 5.56 mmol) and the reaction ws stirred at room temperature overnight. The solvent was removed and then redissolved in 5 mL dry DMF followed by addition of DIPEA (600 muL, 3.44 mmol) and Fmoc-OSu (1.1 g, 3.30 mmol) and the reaction was stirred under N2 at room temperature overnight. DMF was removed under reduced pressure, DCM was added and then the reaction was washed 1* with H2O, 2* with 10% citric acid and brine, dried with MgSO4 and then concentrated. The material was purified via flash chromatography, 0-10% MeOH in H2O to give Fmoc-N-methyl intermediate b. MS=401.2 (M+1).Example 31 Compound 23 (R)-2-((S)-2-cyclohexyl-N-methyl-2-4S)-2-(methylamino)-propanamido)acetamido)-3-methyl-3-(methylthio)-N-(4-phenyl-1, 2, 3-thiadiazol-5-yl)butanamide To a stirred solution of a (55 mg, 0.1 mmol) in 5 mL DMF was added 4-aminomethylpiperidine (60 mul, 0.5 mmol). The reaction was complete after 3 hours and purified by Preparative HPLC to give b. MS=337.0 (M+1).The amine b prepared above was combined with CH2Cl2 (40 mL), saturated aqueous NaHCO3 (40 mL) and cooled to 0 C. Benzyloxy carbonyl chloride (3.0 mL) was then added dropwise and the mixture stirred vigorously overnight.

Molecular Weight:203.24
XLogP3:1.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:5
Exact Mass:203.11575802
Monoisotopic Mass:203.11575802
Topological Polar Surface Area:66.8
Heavy Atom Count:14
Complexity:219
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes