Triethylamine → 4-(2-(2-(3-(Pyridin-2-yldisulfanyl)propanamido)ethoxy)ethoxy)butanoic acid

4-(2-(2-aminoethoxy)ethoxy)butanoic acid (Compound 4) (F.W. 312.37, 100 mg, 0.377 mmole) in 20 mL of anhydrous toluene was azetropically distilled under reduced pressure at 60° C. on a rotary evaporator. The azeotropic distillation was repeated with 20 mL of anhydrous toluene. Then, the resulting residue was dissolved in anhydrous DCM (20 ml). To the above solution was added N-succinimidyl-3-(2-pyridithio) propionate (Compound 5) (SDPD, F.W. 265.3, 100 mg, 0.32 mmole) and triethylamine (105 μl, 0.75 mmole). The mixture was allowed to stand for overnight under stirring at room temperature. TLC showed the disappearance of SPDP. The reaction solution was washed with diluted phosphoric acid (pH4, 5 ml×2). The organic phase was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The resulting residue was subject to flash chromatography on a Biotage system, giving 140 mg of Compound 6, purity>95% (HPLC). 1H NMR in CDCl3, δ ppm: 8.49 (1H, s), 7.74 (1H, d), 7.69 (1H, m), 7.15 (1H, q), 3.80 (2H, t), 3.64 (12H, m), 3.59 (2H, t), 3.46 (2H, dd), 3.07 (2H, t), 2.64 (4H, m). ESI-MS: [M+H]+ 417.

1. distillationThe azeotropic distillation
2. dissolutionThen, the resulting residue was dissolved in anhydrous DCM (20 ml)
3. washThe reaction solution was washed with diluted phosphoric acid (pH4, 5 ml×2)
4. dry with materialThe organic phase was dried over anhydrous Na2SO4
5. concentrationconcentrated under reduced pressure

ORD-Eintrag

ord-d80e6fa67ab74488af409fce5aa42070

Quelldatensatz

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09089610B2