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CAS No.: | 1206102-09-1 |
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Name: | (4R,12aS)-7-(benzyloxy)-4-Methyl-3,4-dihydro-2H-[1,3]oxazino[3,2-d]pyrido[1,2-a]pyrazine-6,8(12H,12aH)-dione |
Article Data: | 5 |
Molecular Structure: | |
Formula: | C19H20N2O4 |
Molecular Weight: | 340.379 |
Synonyms: | (4R,12aS)-7-(benzyloxy)-4-Methyl-3,4-dihydro-2H-[1,3]oxazino[3,2-d]pyrido[1,2-a]pyrazine-6,8(12H,12aH)-dione;Dolutegravir interMediate |
EINECS: | -0 |
PSA: | 60.77000 |
LogP: | 1.95590 |
(R)-3-amino-1-butanol
methyl 1-(2,2-dihydroxyethyl)-4-oxo-3-[(phenylmethyl)oxy]-1,4-dihydro-2-pyridinecarboxylate
(4R,12aS)-7-(benzyloxy)-4-methyl-3,4,12,12a-tetrahydro-2H-pyrido[1′,2’:4,5] pyrazino[2,1-b][1,3]oxazine-6,8-dione
Conditions | Yield |
---|---|
With acetic acid In toluene at 90℃; for 3.5h; | 96% |
With acetic acid In toluene at 90℃; for 2.5h; Product distribution / selectivity; | 83% |
With acetic acid In methanol; toluene at 90℃; for 2.5h; Reagent/catalyst; Temperature; | 83% |
With acetic acid In toluene at 90℃; for 2h; diastereoselective reaction; | 80% |
2-(2-hydroxy-2-phenylethyl)-3-[(phenylmethyl)oxy]-4H-pyran-4-one
(4R,12aS)-7-(benzyloxy)-4-methyl-3,4,12,12a-tetrahydro-2H-pyrido[1′,2’:4,5] pyrazino[2,1-b][1,3]oxazine-6,8-dione
Conditions | Yield |
---|---|
Multi-step reaction with 6 steps 1.1: triethylamine; methanesulfonyl chloride; 1,8-diazabicyclo[5.4.0]undec-7-ene / tetrahydrofuran; 1-methyl-pyrrolidin-2-one / 0.5 h / 30 °C 2.1: rhodium(III) chloride hydrate; sodium periodate; sulfuric acid / water; acetonitrile / 3.5 h / 20 °C 2.2: 1.5 h / 25 °C 3.1: ethanol / 8.5 h / 65 - 80 °C 4.1: sodium hydrogencarbonate / 1-methyl-pyrrolidin-2-one; water / 28 - 35 °C / Large scale 5.1: sodium periodate; sulfuric acid / water; acetonitrile / 1 h / 14 - 17 °C 6.1: acetic acid / methanol; toluene / 2.5 h / 90 °C View Scheme | |
Multi-step reaction with 6 steps 1.1: triethylamine; methanesulfonyl chloride; 1,8-diazabicyclo[5.4.0]undec-7-ene / tetrahydrofuran; 1-methyl-pyrrolidin-2-one / 0.5 h / 30 °C 2.1: rhodium(III) chloride hydrate; sodium periodate; sulfuric acid / water; acetonitrile / 3.5 h / 20 °C 2.2: 1.5 h / 25 °C 3.1: ethanol / 8.5 h / 65 - 80 °C 4.1: sodium hydrogencarbonate / 1-methyl-pyrrolidin-2-one; water / 4 h / 20 °C 5.1: sodium periodate; sulfuric acid / water; acetonitrile / 1 h / 14 - 17 °C 6.1: acetic acid / methanol; toluene / 2.5 h / 90 °C View Scheme | |
Multi-step reaction with 3 steps 1: methanesulfonyl chloride 2: ruthenium trichloride; sodium periodate 3: sodium periodate View Scheme | |
Multi-step reaction with 7 steps 1.1: triethylamine; methanesulfonyl chloride / tetrahydrofuran / 1 h / 20 °C / Large scale 1.2: 1 h / Large scale 2.1: ruthenium trichloride; sodium periodate; sulfuric acid / acetonitrile; water / 20 °C / Large scale 3.1: 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hydrogencarbonate; sodium hypochlorite / acetonitrile; water; ethyl acetate / 20 °C / Large scale 4.1: ethanol / 3.5 h / 65 - 75 °C / Large scale 5.1: sodium hydrogencarbonate / 1-methyl-pyrrolidin-2-one; water / 30 °C / Large scale 6.1: sodium periodate; acetic anhydride / acetonitrile; water / 30 °C / Large scale 7.1: acetic acid / toluene / 2 h / 90 °C View Scheme |
C20H16O3
(4R,12aS)-7-(benzyloxy)-4-methyl-3,4,12,12a-tetrahydro-2H-pyrido[1′,2’:4,5] pyrazino[2,1-b][1,3]oxazine-6,8-dione
Conditions | Yield |
---|---|
Multi-step reaction with 5 steps 1.1: rhodium(III) chloride hydrate; sodium periodate; sulfuric acid / water; acetonitrile / 3.5 h / 20 °C 1.2: 1.5 h / 25 °C 2.1: ethanol / 8.5 h / 65 - 80 °C 3.1: sodium hydrogencarbonate / 1-methyl-pyrrolidin-2-one; water / 28 - 35 °C / Large scale 4.1: sodium periodate; sulfuric acid / water; acetonitrile / 1 h / 14 - 17 °C 5.1: acetic acid / methanol; toluene / 2.5 h / 90 °C View Scheme | |
Multi-step reaction with 5 steps 1.1: rhodium(III) chloride hydrate; sodium periodate; sulfuric acid / water; acetonitrile / 3.5 h / 20 °C 1.2: 1.5 h / 25 °C 2.1: ethanol / 8.5 h / 65 - 80 °C 3.1: sodium hydrogencarbonate / 1-methyl-pyrrolidin-2-one; water / 4 h / 20 °C 4.1: sodium periodate; sulfuric acid / water; acetonitrile / 1 h / 14 - 17 °C 5.1: acetic acid / methanol; toluene / 2.5 h / 90 °C View Scheme | |
Multi-step reaction with 2 steps 1: ruthenium trichloride; sodium periodate 2: sodium periodate View Scheme |
4-oxo-3-[(phenylmethyl)oxy]-4H-pyran-2-carboxylic acid
(4R,12aS)-7-(benzyloxy)-4-methyl-3,4,12,12a-tetrahydro-2H-pyrido[1′,2’:4,5] pyrazino[2,1-b][1,3]oxazine-6,8-dione
Conditions | Yield |
---|---|
Multi-step reaction with 4 steps 1: ethanol / 8.5 h / 65 - 80 °C 2: sodium hydrogencarbonate / 1-methyl-pyrrolidin-2-one; water / 28 - 35 °C / Large scale 3: sodium periodate; sulfuric acid / water; acetonitrile / 1 h / 14 - 17 °C 4: acetic acid / methanol; toluene / 2.5 h / 90 °C View Scheme | |
Multi-step reaction with 4 steps 1: ethanol / 8.5 h / 65 - 80 °C 2: sodium hydrogencarbonate / 1-methyl-pyrrolidin-2-one; water / 4 h / 20 °C 3: sodium periodate; sulfuric acid / water; acetonitrile / 1 h / 14 - 17 °C 4: acetic acid / methanol; toluene / 2.5 h / 90 °C View Scheme | |
Multi-step reaction with 4 steps 1: ethanol / 1 h / Reflux 2: sodium hydrogencarbonate / 1-methyl-pyrrolidin-2-one / 5 h / 20 °C 3: sodium periodate / methanol; water / 1 h / 20 °C 4: acetic acid / toluene / 3.5 h / 90 °C View Scheme | |
Multi-step reaction with 4 steps 1: ethanol / 3.5 h / 65 - 75 °C / Large scale 2: sodium hydrogencarbonate / 1-methyl-pyrrolidin-2-one; water / 30 °C / Large scale 3: sodium periodate; acetic anhydride / acetonitrile; water / 30 °C / Large scale 4: acetic acid / toluene / 2 h / 90 °C View Scheme |
1-(2,3-dihydroxypropyl)-4-oxo-3-[(phenylmethyl)oxy]-1,4-dihydro-2-pyridinecarboxylic acid
(4R,12aS)-7-(benzyloxy)-4-methyl-3,4,12,12a-tetrahydro-2H-pyrido[1′,2’:4,5] pyrazino[2,1-b][1,3]oxazine-6,8-dione
Conditions | Yield |
---|---|
Multi-step reaction with 3 steps 1: sodium hydrogencarbonate / 1-methyl-pyrrolidin-2-one; water / 28 - 35 °C / Large scale 2: sodium periodate; sulfuric acid / water; acetonitrile / 1 h / 14 - 17 °C 3: acetic acid / methanol; toluene / 2.5 h / 90 °C View Scheme | |
Multi-step reaction with 3 steps 1: sodium hydrogencarbonate / 1-methyl-pyrrolidin-2-one; water / 4 h / 20 °C 2: sodium periodate; sulfuric acid / water; acetonitrile / 1 h / 14 - 17 °C 3: acetic acid / methanol; toluene / 2.5 h / 90 °C View Scheme | |
Multi-step reaction with 3 steps 1: sodium hydrogencarbonate / 1-methyl-pyrrolidin-2-one / 5 h / 20 °C 2: sodium periodate / methanol; water / 1 h / 20 °C 3: acetic acid / toluene / 3.5 h / 90 °C View Scheme | |
Multi-step reaction with 3 steps 1: sodium hydrogencarbonate / 1-methyl-pyrrolidin-2-one; water / 30 °C / Large scale 2: sodium periodate; acetic anhydride / acetonitrile; water / 30 °C / Large scale 3: acetic acid / toluene / 2 h / 90 °C View Scheme |
1-(2,3-dihydroxypropyl)-4-oxo-3-[(phenylmethyl)oxy]-1,4-dihydro-2-pyridinecarboxylic acid methyl ester
(4R,12aS)-7-(benzyloxy)-4-methyl-3,4,12,12a-tetrahydro-2H-pyrido[1′,2’:4,5] pyrazino[2,1-b][1,3]oxazine-6,8-dione
Conditions | Yield |
---|---|
Multi-step reaction with 2 steps 1: sodium periodate; sulfuric acid / water; acetonitrile / 1 h / 14 - 17 °C 2: acetic acid / methanol; toluene / 2.5 h / 90 °C View Scheme | |
Multi-step reaction with 2 steps 1: sodium periodate / methanol; water / 1 h / 20 °C 2: acetic acid / toluene / 3.5 h / 90 °C View Scheme | |
Multi-step reaction with 2 steps 1: sodium periodate; acetic anhydride / acetonitrile; water / 30 °C / Large scale 2: acetic acid / toluene / 2 h / 90 °C View Scheme |
Maltol
(4R,12aS)-7-(benzyloxy)-4-methyl-3,4,12,12a-tetrahydro-2H-pyrido[1′,2’:4,5] pyrazino[2,1-b][1,3]oxazine-6,8-dione
Conditions | Yield |
---|---|
Multi-step reaction with 7 steps 1: potassium carbonate / acetonitrile / 5 h / 13 - 80 °C / Large scale 2: bromobenzene; selenium(IV) oxide / 13 h / 140 °C / Dean-Stark 3: sodium chlorite; aminosulfonic acid / water; acetone / 0.67 h / 20 °C / Cooling with ice 4: ethanol / 8.5 h / 65 - 80 °C 5: sodium hydrogencarbonate / 1-methyl-pyrrolidin-2-one; water / 28 - 35 °C / Large scale 6: sodium periodate; sulfuric acid / water; acetonitrile / 1 h / 14 - 17 °C 7: acetic acid / methanol; toluene / 2.5 h / 90 °C View Scheme | |
Multi-step reaction with 7 steps 1: potassium carbonate / acetonitrile / 5 h / 13 - 80 °C / Large scale 2: bromobenzene; selenium(IV) oxide / 13 h / 140 °C / Dean-Stark 3: sodium chlorite; aminosulfonic acid / water; acetone / 0.67 h / 20 °C / Cooling with ice 4: ethanol / 8.5 h / 65 - 80 °C 5: sodium hydrogencarbonate / 1-methyl-pyrrolidin-2-one; water / 4 h / 20 °C 6: sodium periodate; sulfuric acid / water; acetonitrile / 1 h / 14 - 17 °C 7: acetic acid / methanol; toluene / 2.5 h / 90 °C View Scheme | |
Multi-step reaction with 8 steps 1.1: potassium carbonate / acetonitrile / 5 h / 13 - 80 °C / Large scale 2.1: lithium hexamethyldisilazane / tetrahydrofuran / 2 h / -60 °C 2.2: 1 h / -60 °C 3.1: triethylamine; methanesulfonyl chloride; 1,8-diazabicyclo[5.4.0]undec-7-ene / tetrahydrofuran; 1-methyl-pyrrolidin-2-one / 0.5 h / 30 °C 4.1: rhodium(III) chloride hydrate; sodium periodate; sulfuric acid / water; acetonitrile / 3.5 h / 20 °C 4.2: 1.5 h / 25 °C 5.1: ethanol / 8.5 h / 65 - 80 °C 6.1: sodium hydrogencarbonate / 1-methyl-pyrrolidin-2-one; water / 28 - 35 °C / Large scale 7.1: sodium periodate; sulfuric acid / water; acetonitrile / 1 h / 14 - 17 °C 8.1: acetic acid / methanol; toluene / 2.5 h / 90 °C View Scheme |
3-(benzyloxy)-4-oxo-4H-pyran-2-carbaldehyde
(4R,12aS)-7-(benzyloxy)-4-methyl-3,4,12,12a-tetrahydro-2H-pyrido[1′,2’:4,5] pyrazino[2,1-b][1,3]oxazine-6,8-dione
Conditions | Yield |
---|---|
Multi-step reaction with 5 steps 1: sodium chlorite; aminosulfonic acid / water; acetone / 0.67 h / 20 °C / Cooling with ice 2: ethanol / 8.5 h / 65 - 80 °C 3: sodium hydrogencarbonate / 1-methyl-pyrrolidin-2-one; water / 28 - 35 °C / Large scale 4: sodium periodate; sulfuric acid / water; acetonitrile / 1 h / 14 - 17 °C 5: acetic acid / methanol; toluene / 2.5 h / 90 °C View Scheme | |
Multi-step reaction with 5 steps 1: sodium chlorite; aminosulfonic acid / water; acetone / 0.67 h / 20 °C / Cooling with ice 2: ethanol / 8.5 h / 65 - 80 °C 3: sodium hydrogencarbonate / 1-methyl-pyrrolidin-2-one; water / 4 h / 20 °C 4: sodium periodate; sulfuric acid / water; acetonitrile / 1 h / 14 - 17 °C 5: acetic acid / methanol; toluene / 2.5 h / 90 °C View Scheme | |
Multi-step reaction with 5 steps 1: 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hydrogencarbonate; sodium hypochlorite / acetonitrile; water; ethyl acetate / 20 °C / Large scale 2: ethanol / 3.5 h / 65 - 75 °C / Large scale 3: sodium hydrogencarbonate / 1-methyl-pyrrolidin-2-one; water / 30 °C / Large scale 4: sodium periodate; acetic anhydride / acetonitrile; water / 30 °C / Large scale 5: acetic acid / toluene / 2 h / 90 °C View Scheme |
benzyl bromide
(4R,12aS)-7-(benzyloxy)-4-methyl-3,4,12,12a-tetrahydro-2H-pyrido[1′,2’:4,5] pyrazino[2,1-b][1,3]oxazine-6,8-dione
Conditions | Yield |
---|---|
Multi-step reaction with 7 steps 1: potassium carbonate / acetonitrile / 5 h / 13 - 80 °C / Large scale 2: bromobenzene; selenium(IV) oxide / 13 h / 140 °C / Dean-Stark 3: sodium chlorite; aminosulfonic acid / water; acetone / 0.67 h / 20 °C / Cooling with ice 4: ethanol / 8.5 h / 65 - 80 °C 5: sodium hydrogencarbonate / 1-methyl-pyrrolidin-2-one; water / 28 - 35 °C / Large scale 6: sodium periodate; sulfuric acid / water; acetonitrile / 1 h / 14 - 17 °C 7: acetic acid / methanol; toluene / 2.5 h / 90 °C View Scheme | |
Multi-step reaction with 7 steps 1: potassium carbonate / acetonitrile / 5 h / 13 - 80 °C / Large scale 2: bromobenzene; selenium(IV) oxide / 13 h / 140 °C / Dean-Stark 3: sodium chlorite; aminosulfonic acid / water; acetone / 0.67 h / 20 °C / Cooling with ice 4: ethanol / 8.5 h / 65 - 80 °C 5: sodium hydrogencarbonate / 1-methyl-pyrrolidin-2-one; water / 4 h / 20 °C 6: sodium periodate; sulfuric acid / water; acetonitrile / 1 h / 14 - 17 °C 7: acetic acid / methanol; toluene / 2.5 h / 90 °C View Scheme | |
Multi-step reaction with 8 steps 1.1: potassium carbonate / acetonitrile / 5 h / 13 - 80 °C / Large scale 2.1: lithium hexamethyldisilazane / tetrahydrofuran / 2 h / -60 °C 2.2: 1 h / -60 °C 3.1: triethylamine; methanesulfonyl chloride; 1,8-diazabicyclo[5.4.0]undec-7-ene / tetrahydrofuran; 1-methyl-pyrrolidin-2-one / 0.5 h / 30 °C 4.1: rhodium(III) chloride hydrate; sodium periodate; sulfuric acid / water; acetonitrile / 3.5 h / 20 °C 4.2: 1.5 h / 25 °C 5.1: ethanol / 8.5 h / 65 - 80 °C 6.1: sodium hydrogencarbonate / 1-methyl-pyrrolidin-2-one; water / 28 - 35 °C / Large scale 7.1: sodium periodate; sulfuric acid / water; acetonitrile / 1 h / 14 - 17 °C 8.1: acetic acid / methanol; toluene / 2.5 h / 90 °C View Scheme |
3-O-benzylmaltol
(4R,12aS)-7-(benzyloxy)-4-methyl-3,4,12,12a-tetrahydro-2H-pyrido[1′,2’:4,5] pyrazino[2,1-b][1,3]oxazine-6,8-dione
Conditions | Yield |
---|---|
Multi-step reaction with 6 steps 1: bromobenzene; selenium(IV) oxide / 13 h / 140 °C / Dean-Stark 2: sodium chlorite; aminosulfonic acid / water; acetone / 0.67 h / 20 °C / Cooling with ice 3: ethanol / 8.5 h / 65 - 80 °C 4: sodium hydrogencarbonate / 1-methyl-pyrrolidin-2-one; water / 28 - 35 °C / Large scale 5: sodium periodate; sulfuric acid / water; acetonitrile / 1 h / 14 - 17 °C 6: acetic acid / methanol; toluene / 2.5 h / 90 °C View Scheme | |
Multi-step reaction with 6 steps 1: bromobenzene; selenium(IV) oxide / 13 h / 140 °C / Dean-Stark 2: sodium chlorite; aminosulfonic acid / water; acetone / 0.67 h / 20 °C / Cooling with ice 3: ethanol / 8.5 h / 65 - 80 °C 4: sodium hydrogencarbonate / 1-methyl-pyrrolidin-2-one; water / 4 h / 20 °C 5: sodium periodate; sulfuric acid / water; acetonitrile / 1 h / 14 - 17 °C 6: acetic acid / methanol; toluene / 2.5 h / 90 °C View Scheme | |
Multi-step reaction with 7 steps 1.1: lithium hexamethyldisilazane / tetrahydrofuran / 2 h / -60 °C 1.2: 1 h / -60 °C 2.1: triethylamine; methanesulfonyl chloride; 1,8-diazabicyclo[5.4.0]undec-7-ene / tetrahydrofuran; 1-methyl-pyrrolidin-2-one / 0.5 h / 30 °C 3.1: rhodium(III) chloride hydrate; sodium periodate; sulfuric acid / water; acetonitrile / 3.5 h / 20 °C 3.2: 1.5 h / 25 °C 4.1: ethanol / 8.5 h / 65 - 80 °C 5.1: sodium hydrogencarbonate / 1-methyl-pyrrolidin-2-one; water / 28 - 35 °C / Large scale 6.1: sodium periodate; sulfuric acid / water; acetonitrile / 1 h / 14 - 17 °C 7.1: acetic acid / methanol; toluene / 2.5 h / 90 °C View Scheme |