Taltirelin intermediate and synchronizing method of taltirelin
A synthesis method and technology of methyl hydrogenated milk are applied in the field of synthesis of tatirelin intermediates and tatirelin, and can solve the problems of complex synthesis process operation, low application value, unfavorable industrial production and the like, and achieve a reaction system. Simple, cost-effective, easy-to-handle effects
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1
[0062] Embodiment 1, the preparation of hydrogenated lactic acid
[0063] 1. Add L-Asn.H 2 O (15.013g, 100mmol) and Et 3 N (23.274g, 230mmol) was dissolved in water (200ml), and ethyl chloroformate (24.962g, 230mmol) was added dropwise while stirring at room temperature. After the addition was complete, the reaction was continued for two hours, and the pH of the mixed solution was adjusted to 2. Extracted with ethyl acetate, the organic phase was washed three times with saturated brine, dried and then spin-dried to obtain 16.334 g of white solid, yield: 80%, purity: 96%, MS: 204,227.
[0064] 2. Set N α -Ethoxycarbonyl asparagine (16.334g, 80mmol) was added to the ethanol solution of metal Na (3.68g, 160mmol), refluxed for 4 hours, the ethanol was spinned off, the residue was dissolved in water, acidified with dilute hydrochloric acid to pH=2, Then it was extracted with ethyl acetate, and the organic phase was washed twice with water, dried and concentrated. The resulting ...
Embodiment 2
[0065] The preparation of embodiment 2,3-methylhydroorotic acid
[0066] 1. Add Et 3 N (25.298g, 250mmol) and benzyl bromide (34.206g, 200mmol) were added to the DMF suspension of hydrogenated orotic acid (15.811g, 100mmol), and stirred at room temperature for two days. The reaction solution was poured into a large amount of ice water, and the obtained solid was filtered and dried, and then recrystallized with MeOH to obtain 20.6 g of colorless crystals. Yield: 83%, Purity: 98%, MS: 248,271.
[0067] 2. Add 70% NaH (2.02g, 62mmol) into the mixture of MeI (43.31g, 310mmol) and benzyl hydrogenated orotate (15.3g, 62mmol), react for 4 hours under stirring at room temperature, thin layer chromatography shows that the raw material The response is complete. The reaction solution was poured into ice water, filtered and dried, and the obtained solid was washed twice with ethyl acetate to obtain 8.52 g of white solid. Yield: 53%, Purity: 97.5%, MS: 262,285.
[0068] 3. Add 10% Pd-...
Embodiment 3
[0069] Example 3, L-His-L-Pro-NH 2 preparation of
[0070] 1. Mix L-Boc-His(Trt)-OH (9.952g, 20mmol), L-Pro-NH 2 (2.283g, 20mmol) and DCC (4.326g, 21mmol) were dissolved in DCM (200ml), stirred at room temperature for 2 hours, TLC showed that the reaction was complete. The solid was filtered off, the filtrate was spin-dried and recrystallized with EA-PE to obtain 6.6 g of white solid. Yield: 55.6%, purity 91%, MS: 594.
[0071] 2. Add L-Boc-His(Trt)-L-Pro-NH 2 (6.6g, 11mmol) was added to 66ml of TFA solution, stirred and reacted for one hour under ice-bath conditions, and thin-layer chromatography showed that the reaction of raw materials was complete. The reaction solution was poured into 10 times the amount of anhydrous ether, centrifuged, washed twice with anhydrous ether, and dried in vacuo to obtain 4.32 g of a white solid. Yield: 82%, MS: 251.
PUM
Login to View More Abstract
Description
Claims
Application Information
Login to View More