ChemicalBook CAS DataBase List O-Methyl Dolutegravir

O-Methyl Dolutegravir synthesis

6synthesis methods

Product Name:O-Methyl Dolutegravir
CAS Number:1335210-35-9
Molecular formula:C21H21F2N3O5
Molecular Weight:433.41

(3S,11aR)-3-methyl-6-(methyloxy)-5,7-dioxo-2,3,5,7,11,11a- hexahydro[1,3]oxazolo [3,2-a]pyrido[1,2-d]pyrazine-8-carboxylic acid (100 gm) and carbonyl dimidazole (78.89 gm) was suspended in acetonitrile (1000 mL). The mixture was heated to 75°C and stirred for 1 hour. The resulting solution was cooled to a temperature of 20°C and treated with 2,4- difluorobenzyl amine solution (55.2 gm was dissolved in 200 mL of acetonitrile). The reaction mixture was maintained for 2 hours, concentrated, and the compound was extracted with ethyl acetate (1000 mL). Isopropyl alcohol (500 mL) was added at 40°C, stirred the reaction mass for 30 minutes at a temperature of 50°C, and cooled the reaction mass to 25°C. The reaction mixture was maintained for 8 hours at the same temperature. The product O-Methyl Dolutegravir was collected by filtration and dried under vacuum (85 gm).

1335210-34-8 Synthesis

(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

1335210-34-8
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72235-52-0 Synthesis

72235-52-0
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1335210-35-9
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Yield:1335210-35-9 78%

Reaction Conditions:

with 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride in acetonitrile at 80; for 5 h;

Steps:

3 Example 3. Preparation of Compound 7

Compound 6 (0.6 g, 1.95 mmol),1-ethyl-(3-dimethylaminopropyl)carbonic acid diimine hydrochloride (EDCI, 0.51 g, 2.65 mmol),2,4-difluorobenzylamine (0.29 ml, 2.44 mmol) in acetonitrile (10 ml) was heated to 80 ° C for 5 h.The reaction was quenched by the addition of 6 ml of water, the lower layer was a viscous yellow oily liquid, and the upper layer was suspended.The solvent of acetonitrile was evaporated under reduced pressure and suction filtered to give a crude material (yel.The crude product was recrystallized from AcOEt/petroleum ether = 4/1 solvent 15 ml to give compound 7 0.66 g(Rf = 0.25, TLC developer: AcOEt),The yield was 78%.

References:

CN109293675,2019,A Location in patent:Paragraph 0004; 0035-0036

61477-40-5 Synthesis