反応 #1994335

反応方程式

1,1,3,3-tetramethylurea

chloride

→

N-[chloro(dimethylamino)methylene]-N-methylmethanaminium chloride salt

溶媒

ether

反応条件

後処理

1. 1
   workup.WAITthe mixture was left
2. 2
   その他After 5 minutes a solid had precipitated on the base of the flask
3. 3
   workup.STIRRINGstirring
4. 4
   その他Volatiles were evaporated

実験手順

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]+

出典