A kind of tetrahydrooxazolopyridoazepine ketone derivative and use thereof
A technology of tetrahydrooxazole and azapinone, applied in the field of tetrahydrooxazolopyridoazepinone derivatives
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1
[0106] Preparation of Compound A:
[0107] Under the condition of temperature -10℃, dissolve 57.3ml of sodium nitrite, 0.83mol and 100g of ethyl cyanoacetate, 0.83mol of ethyl cyanoacetate in 700ml of pure water, and slowly add 36.6ml of 85% concentrated phosphoric acid, 0.055mol dropwise for a period of time. Continue for 3 hours, heat up to 45 ° C and stir for 1 hour, then add 74 ml of concentrated hydrochloric acid, 0.88 mol, continue to stir overnight at a temperature of 0 ° C, a large amount of white solid is precipitated, and the white compound A is 2-cyano-2- Ethyl hydroxyiminoacetate, does not need to be purified for the next step reaction;
[0108] Preparation of Compound B:
[0109] At room temperature, the obtained white compound A was 43 g of ethyl 2-cyano-2-hydroxyiminoacetate, 0.3 mol of which was dissolved in 500 ml of pure water, and 350 ml of saturated sodium bicarbonate solution was slowly added dropwise with stirring. , then add 156 g of sodium dithionite,...
Embodiment 2
[0162] Preparation of compounds D1-D48:
[0163] 10 mmol of each compound C1-C48 obtained in Example 1 was dissolved in anhydrous dichloromethane, then 10 mL of trifluoroacetic acid was slowly added dropwise, the reaction was carried out at room temperature until all the raw materials disappeared, the reaction solution was concentrated, and a normal silica gel column chromatography gradient was used. Elution, the eluent is the petroleum ether of volume ratio 2:1: ethyl acetate, respectively obtains compound D1-D48, wherein the name of compound D1-D48 is:
[0164] Compound D1 is 2-methyl-5-amino-4-carboxylic acid ethyl ester oxazole, yield: 84%, pale yellow solid;
[0165] 1 H NMR (400MHz, CDCl 3 )δ5.31(s, 2H), 4.33(q, J=7.2Hz, 2H), 2.34(s, 3H), 1.37(t, J=7.1Hz, 3H);
[0166] Compound D2 is 2-ethyl-5-amino-4-carboxylic acid ethyl ester oxazole, yield: 80%, pale yellow solid;
[0167] 1 H NMR (400MHz, CDCl 3 )δ5.58(s, 2H), 4.25(q, J=7.1Hz, 2H), 2.58(q, J=7.6Hz, 2H), 1.28(t...
Embodiment 3
[0260] Preparation of compound E1:
[0261] The compound D1 obtained in Example 2 is 2-methyl-5-amino-4-carboxylic acid ethyl ester 0.17 g, 10 mmol of oxazole was dissolved in 20 mL of anhydrous dioxane, and 0.17 g of cyclohexanamide, 15 mmol was added , then slowly add phosphorus oxychloride 0.38g, 2.5mmol, reflux reaction until all the raw materials disappear, extract with dichloromethane, dry over anhydrous sodium sulfate, concentrate under reduced pressure, use normal silica gel column chromatography gradient elution, wash The removal agent is petroleum ether: ethyl acetate with a volume ratio of 1:1, and the obtained compound E1 is 2-methyl-6,7,8,9-tetrahydrooxazolo[5',4':4,5]pyridine And[1,2-a]azepin-11(5H)-one, yield 75%, pale yellow solid, melting point: 73-75℃;
[0262] 1 H NMR (400MHz, CDCl 3 )δ4.42(t, J=6.1Hz, 2H), 3.08(t, J=6.6Hz, 2H), 2.57(s, 3H), 2.02–1.61(m, 6H).
PUM
Login to View More Abstract
Description
Claims
Application Information
Login to View More