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CAS No. : | 3651-67-0 | MDL No. : | MFCD00039042 |
Formula : | C5H12ClNO | Boiling Point : | No data available |
Linear Structure Formula : | - | InChI Key : | BTJRKNUKPQBLAL-UHFFFAOYSA-N |
M.W : | 137.61 | Pubchem ID : | 3083815 |
Synonyms : |
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Signal Word: | Warning | Class: | |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | With 4-methyl-morpholine; isobutyl chloroformate; In ethyl acetate; at -15 - 20℃; for 3.5h; | A solution comprising 290 mg (0.71 mmol) of <strong>[27486-87-9]N-acetyl-S-trityl-L-cysteine</strong> (7, Bachem) and 80 mul (0.72 mmol) of of N-methylmorpholine (NMM) in 5 ml of AcOEt is stirred at -15 C. and then 93 mul (0.71 mmol) of isobutyl chloroformate are added. After stirring for 15 min and while maintaining the starting temperature, 111.4 mg (0.71 mmol) of S-acetylcysteamine hydrochloride (prepared according to T. Wieland and E. Bokelman, Ann. Chem., 1952, 576, 20-34) and then 80 mul (0.72 mmol) of NMM are added. The reaction mixture is maintained at -15 C. for 15 min and then, after returning to room temperature, stirring is continued for 3 h. The NMM hydrochloride formed is filtered off and washed with 2×2.5 ml of AcOEt and the combined organic phases are evaporated to dryness under vacuum. The coupling product is subsequently isolated from the gum obtained by flash chromatography on a silica gel column (eluent: AcOEt/petroleum ether 30%). 198 mg (Yd=55%) of the expected compound are collected. Rf (AcOEt/petroleum ether, 9:1): 0.41. Cystallizes from an AcOEt/petroleum ether mixture in the form of a colorless powder: M.p.=111-113 C. [alpha]D20=+10.5 (c 0.8, CHCl3). [0155] 1H NMR (CDCl3) delta ppm: 1.90 (s, 3H, NCOCH3), 2.29 (s, 3H, SCOCH3), 2.48 (dd, J=5.7, 12.9 Hz, 1H, beta Ha cys), 2.82 (dd, J=6.4, 12.9 Hz, 1H, beta Hb cys), 2.92-3.01 (m, 2H, NCH2CH2S), 3.32-3.42 (m, 2H, NCH2CH2S), 4.07-4.20 (m, 1H, alpha H cys), 5.70 (d, J=7.6 Hz, 1H, NH cys), 6.34 (t, J=5.5 Hz, 1H, NHCH2), 7.19-7.35 and 7.40-7.47 (2 m, 15H, aromatic H). MS: (FAB+/NBA+K+) m/z 545 (M+K)+, 507 (M+H)+; (FAB-/NBA) m/z 505 (M-H)-. [TABLE-US-00001] Analysis: C28H30N2O3S2 (506) Calc. %: C 66.40 H 5.93 N 5.53 Found %: 66.17 6.00 5.81 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 4-methyl-morpholine; isobutyl chloroformate; In ethyl acetate; at -15℃; for 2.5h; | A solution comprising 1.5 g (3.70 mmol) of 7 and 410 mul (3.73 mmol) of NMM in 30 ml of AcOEt is stirred at -15 C. and then 480 mul (3.70 mmol) of isobutyl chloroformate are added. After stirring for 15 min and while maintaining the starting temperature, 426 mg (3.70 mmol) of N-hydroxysuccinimide are added. The reaction mixture is maintained at -15 C. for 15 min and then, after returning to ambient temperature, stirring is continued for 2 h. The NMM hydrochloride formed is filtered off and washed with 2×5 ml of AcOEt. The organic phases comprising the O-N-succinimide active ester of 7 are combined and stirred at -15 C. 575 mg (3.70 mmol) of S-acetylcysteamine hydrochloride and 410 mul (3.73 mmol) of NMM are then successively added to the solution. The reaction mixture is maintained at -15 C. for 15 min and then, after returning to ambient temperature, stirring is continued for 12 h. The solution is subsequently diluted with 300 ml of AcOEt, washed (water, 30 ml; ice-cold saturated sodium bicarbonate, 30 ml; water, 30 ml; ice-cold 0.1N citric acid, 30 ml; water, 3×30 ml), dried over sodium sulfate, filtered and evaporated to dryness under vacuum. The residue obtained is subsequently purified as above to give, with a yield of 70% (1.31 g) and with entirely the same physicochemical criteria, the coupling product 8 described above. |