ChemicalBook CAS DataBase List (4R,12aS)-7-Methoxy-4-Methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-[1,3]oxazino[3,2-d]pyrido[1,2-a]pyrazine-9-carboxylic acid

(4R,12aS)-7-Methoxy-4-Methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-[1,3]oxazino[3,2-d]pyrido[1,2-a]pyrazine-9-carboxylic acid synthesis

5synthesis methods

Product Name:(4R,12aS)-7-Methoxy-4-Methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-[1,3]oxazino[3,2-d]pyrido[1,2-a]pyrazine-9-carboxylic acid
CAS Number:1335210-34-8
Molecular formula:C14H16N2O6
Molecular Weight:308.29

5-methoxy-6-(methoxycarbonyl)-4-oxo-1-(2-oxoethyl)-1,4-dihydropyridine-3-carboxylic acid (3.38 g, 107.24 mmol) was dissolved in 33 ml of acetonitrile. Add glacial acetic acid (3 ml) and methanesulfonic acid (0.21 ml, 3.24 mmol) in a 150 ml round bottom flask at room temperature. The reaction was heated to 60 ° C for 19 h. (R)-3-Amino-1-butanol (1.44 ml, 1.34 g, dissolved in 2.25 ml of CH3CN) was slowly added dropwise to the above reaction solution. The reaction was continued to stir at 60 ° C for 18 h to give a white suspension. The reaction solution was concentrated to dryness under reduced pressure to give a concentrate. Add 25 ml of CH2Cl2 and 1N HCl (25 ml). The organic layer was separated, and the aqueous layer was extracted with CH 2 Cl 2 (25 ml x 2). The organic layers were combined and concentrated to dryness under reduced pressure to give crude 6 2.2g. The crude product was recrystallized from 15 ml of MeOH/petroleum ether = 6/1 solvent. After filtration and drying, a pale yellow solid product of (4R,12aS)-7-Methoxy-4-Methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-[1,3]oxazino[3,2-d]pyrido[1,2-a]pyrazine-9-carboxylic acid was obtained, 1.72 g.

(4R,12aS)-7-Methoxy-4-Methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-[1,3]oxazino[3,2-d]pyrido[1,2-a]pyrazine-9-carboxylic acid

61477-40-5 Synthesis

61477-40-5
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$15.00/1g

1335210-23-5 Synthesis

1-(2,2-diMethoxyethyl)-5-Methoxy-6-(Methoxycarbonyl)-4-oxo-1,4-dihydropyridine-3-carboxylic acid

1335210-23-5
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$5.00/250mg

1335210-34-8
68 suppliers
$1296.00/1g

Yield:1335210-34-8 65%

Reaction Conditions:

with methanesulfonic acid;glacial acetic acid in acetonitrile; for 15 h;Reflux;

Steps:

3 Example 3. Preparation of compound VIb (intermediate for synthesizing Dolutegravir)

The intermediate acetal obtained in Example 1 (compound 4, 20 g, 63 mmol) was weighed and dissolved in 100 mL of CH3CN.HOAc (100 mL) and CH3SO3H (1.2 mL, 18.5 mmol) and (R)-3-amino-1-butanol (16.73 g, 188 mmol) in CH3CN (100 mL) were added at room temperature, and the mixture was refluxed for 15 hours.The mixture was concentrated, and the residue was redissolved in CH2Cl2 (200 mL).Dilute HCl (IN, 100 mL) was added and the layers were separated.The aqueous layer was extracted with CH2Cl2 (100 mL x 2), and the organic layers were combined and concentrated. MeOH (50 mL) was added and the resulting mixture was heated to reflux for 2 hours, a yellow solid precipitated from the reaction.The reaction was stopped, cooled to room temperature, and the product was collected by filtration and dried in vacuo to give the title compound VIb (12.6 g, 65% yield) as a yellow solid.

References:

CN114605437,2022,A Location in patent:Paragraph 0017; 0041-0042

41051-15-4 Synthesis