Boc-5-aminopentanoic acid

Boc-NH-C4-acid is a PROTAC linker, which belongs to a Alkyl/ether linker. Boc-NH-C4-acid can be used in the synthesis of the compound PROTAC1, and specifically degrades EED, EZH2, and SUZ12 in the PRC2 Complex.

To a solution containing 5-aminovaleric acid (5.85 g, 0, 05 mol) in 100 ml of 2 percent aqueous sodium hydroxide and 100 mi of dioxane was drop wise added a solution containing di-t- butyldicarbonate (10.9 g, 0.05 mol) in 40 ml of dioxane. The reaction mixture was stirred for 18 hours and then acidified to Η 3 using I N hydrochloric acid. The acidified mixture was extracted three times with dichloromethane. The organic layers were combined, washed with water, and dried over anhydrous sodium sulfate to yield 10.1 g (93.5percent yield) of the desired compound as a white crystalline solid, m.p. 47-49°CTo a stirred solution of 5-aminovaleric acid (1.5g, 12.8mmol) and sodium hydrogen carbonate (2.69g, 32.0mmol) in deionised water (25mL) was added di-tert-butyl dicarbonate (3.35g, 15.4mmol) in 1, 4-dioxane (25mL) and left to stir at rt for 24h. The resultant mixture was filtered and the filtrate washed with diethyl ether (25ml). The aqueous layer was reduced to pH 2 through the addition of aqueous hydrochloric acid (∼7mL, 2M) and then extracted with ethyl acetate (3×15mL). The organic extract was dried over MgSOMethyl 5-[(tert-butoxicarbonyl)amino]valerate 14 (1.858 g;8.04 mmol) was dissolved in 40 mL of a THF/H2O 4:1 mixture. LiOH(231 mg; 9.65 mmol) was added to the solution. Mixture wasallowed to react overnight at room temperatureTHF was evaporatedunder vacuum, H2O (8 mL) added to the resulting mixtureand acidified to pH = 1–2. Aqueous phase was extracted withEtOAc (3 25 mL). Combined organic phases were washed withbrine, dried over anhydrous Na2SO4, filtered and solvent evaporatedunder vacuum. Final product yielded a white solid (1.648 g;94percent). Rf 0.4 (Hex/EtOAc 1:1); 1H NMR (MeOD, 400 MHz) d 3.05–3.08 (t, J = 6.9 Hz, 2H), 2.31–2.34 (t, J = 7.1 Hz, 2H), 1.60–1.67 (m, 2H), 1.50–1.55 (m, 2H), 1.45 (s, 9H); 13C NMR (MeOD, 100 MHz)d 176.0, 157.1, 78.4, 39.5, 33.1, 29.0, 27.4, 21.8; MS (ESI), m/z calculatedfor [C10H19NO4 + Na+] = 240.1; found 240.1.Example 5

Molecular Weight:217.26
XLogP3:1.1
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:7
Exact Mass:217.13140809
Monoisotopic Mass:217.13140809
Topological Polar Surface Area:75.6
Heavy Atom Count:15
Complexity:220
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes