Chloride → [Chloro(dimethylamino)methylidene]-dimethylazanium chloride

1,1,3,3-tetramethylurea (450 mg) was dissolved in anhydrous ether (5 mL) under N2. Oxayl chloride (390 uL) was added over 1 minute and the mixture was left to stir. After 5 minutes a solid had precipitated on the base of the flask, this was broken up and stirring was continued overnight. Volatiles were evaporated to give N-[chloro(dimethylamino)methylene]-N-methylmethanaminium chloride salt as a white solid. Acetonitrile (10 mL) was added and 1 mL of this solution was added to a stirred solution of O-benzyl-2,6-dimethyl-L-tyrosyl-N-[(2S)-2-{[(Z)-{[(benzyloxy)carbonyl]amino}{[(benzyloxy)carbonyl]imino}methyl]amino}-3-phenylpropyl]-D-alaninamide (315 mg, 0.387 mmol) from preparation 23, and triethylamine (65 uL, 0.464 mmol) in acetonitrile (2 mL) under N2 with ice cooling. The reaction mixture was then allowed to stir at room temperature overnight. LCMS showed starting material still remained so more of the N-[chloro(dimethylamino)methylene]-N-methylmethanaminium chloride salt solution (0.1 mL) was added and the reaction was left to stir over a weekend. The reaction mixture was then purified by Trilution HPLC (eluting with acetonitrile/H2O/formic acid gradient) to afford the title compound as a white foam in 24% yield, 90 mg. 1H NMR (400 MHz, MeOH-d4) δ : 0.92 (d, 3H), 2.28 (S, 6H), 2.60-3.20 (m, 17H), 3.48 (m, 1H), 4.04 (m, 2H), 4.44 (m, 1H), 5.04 (s, 4H), 5.22 (s, 2H), 6.69 (s, 2H), 7.18-7.41 (m, 20H), 8.27 (s, 1H). LRMS ES m/z 912 [MH]+

1. waitthe mixture was left
2. customAfter 5 minutes a solid had precipitated on the base of the flask
3. stirringstirring
4. customVolatiles were evaporated

ORD-Eintrag

ord-65c02f26d7c24baaa2ea82ea29f1d751

Quelldatensatz

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08598123B2