(4R,12aS)-N-(2,4-difluorobenzyl)-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-carboxamide

Base Information

• Chemical Name: (4R,12aS)-N-(2,4-difluorobenzyl)-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-carboxamide
• CAS No.: 1335210-35-9
• Molecular Formula: C21H21F2N3O5
• Molecular Weight: 433.412
• European Community (EC) Number: 838-070-7
• Mol file: 1335210-35-9.mol

Synonyms:1335210-35-9;(4R,12aS)-N-(2,4-difluorobenzyl)-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-carboxamide;(4R,12AS)-N-(2,4-difluorobenzyl)-7-methoxy-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazine-9-carboxamide;(3S,7R)-N-[(2,4-Difluorophenyl)methyl]-11-methoxy-7-methyl-9,12-dioxo-4-oxa-1,8-diazatricyclo[8.4.0.03,8]tetradeca-10,13-diene-13-carboxamide;SCHEMBL15082128;AMY30025;DS-12374;CS-0186080;F11522;A855642;(4R,12AS)-N-(2,4-difluorobenzyl)-7-methoxy-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazine-9-ca;(4R,12aS)-N-[(2,4-Difluorophenyl)methyl]-3,4,6,8,12,12a-hexahydro-7-methoxy-4-methyl-6,8-dioxo-2H-pyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazine-9-carboxamide

Chemical Property of (4R,12aS)-N-(2,4-difluorobenzyl)-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-carboxamide

Chemical Property:

• Boiling Point: 684.3±55.0 °C(Predicted)
• PKA: 10.70±0.40(Predicted)
• PSA: 89.87000
• Density: 1.45±0.1 g/cm3(Predicted)
• LogP: 1.98460
• Storage Temp.: Sealed in dry,Room Temperature
• XLogP3: 2.2
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 8
• Rotatable Bond Count: 4
• Exact Mass: 433.14492710
• Heavy Atom Count: 31
• Complexity: 845

Purity/Quality:

98% MIN ^*data from raw suppliers

O-MethylDolutegravir ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC1CCOC2N1C(=O)C3=C(C(=O)C(=CN3C2)C(=O)NCC4=C(C=C(C=C4)F)F)OC
• Isomeric SMILES: C[C@@H]1CCO[C@@H]2N1C(=O)C3=C(C(=O)C(=CN3C2)C(=O)NCC4=C(C=C(C=C4)F)F)OC
• Description: Dolutegravir intermediate is a new synthetic intermediate of Dolutegravir. Dolutegravir is an integrase inhibitor used to treat human immunodeficiency virus (HIV)-1 infection.
• Uses: (4R,12AS)-N-(2,4-Difluorobenzyl)-7-methoxy-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido[1'',2'':4,5]pyrazino[2,1-b][1,3]oxazine-9-carboxamide is an intermediate in the preparation of dolutegravir, an integrase inhibitor for HIV-1 infection therapy.

Technology Process of (4R,12aS)-N-(2,4-difluorobenzyl)-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-carboxamide

There total 32 articles about (4R,12aS)-N-(2,4-difluorobenzyl)-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-carboxamide which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 78.0%

(4R,12aS)-7-methoxy-4-methyl-6,8-dioxo-3,4,6,8, 12,12a-hexahydro-2H-pyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazine-9-carboxylic acid (1335210-34-8) + 2,4-Difluoro-benzylamine (72235-52-0) → (4R,12aS)-N-(2,4-difluorobenzyl)-7-methyloxy-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido [1',2',:4,5]pyrazino[2,1-b] [1,3]oxazine-9-carboxamide (1335210-35-9)

Guidance literature:

With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In acetonitrile; at 80 ℃; for 5h;

Reference yield:

(R)-3-amino-1-butanol (61477-40-5) + methyl 5-(2,4-difluorobenzylcarbamoyl)-3-methoxy-4-oxo-1-(2-oxoethyl)-1,4-dihydropyridine-2-carboxylate → (4R,12aS)-N-(2,4-difluorobenzyl)-7-methyloxy-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido [1',2',:4,5]pyrazino[2,1-b] [1,3]oxazine-9-carboxamide (1335210-35-9)

Guidance literature:

With acetic acid; In acetonitrile; at 70 ℃; for 12h; Inert atmosphere;

Reference yield:

2,4-difluorobenzaldehyde (1550-35-2) + (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-carboxamide → (4R,12aS)-N-(2,4-difluorobenzyl)-7-methyloxy-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido [1',2',:4,5]pyrazino[2,1-b] [1,3]oxazine-9-carboxamide (1335210-35-9)

Guidance literature:

With triethylsilane; trifluoroacetic acid; In toluene; Reflux;

upstream raw materials:

methyl 2-[(dimethylamino)methylene]-4-methoxy-3-oxobutanoate

methyl 2-(((2,2-dimethoxyethyl)amino)methylene)-4-methoxy-3-oxobutanoate

(4R,12aS)-7-methoxy-4-methyl-6,8-dioxo-3,4,6,8, 12,12a-hexahydro-2H-pyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazine-9-carboxylic acid

2,4-Difluoro-benzylamine

Downstream raw materials:

dolutegravir

(4R,12aS)-N-(2,4-difluorobenzyl)-7-hydroxy-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido[1′,2′:4,5]pyrazino-[2,1-b][1,3]oxazine-9-carboxamide sodium salt

Refernces

• 1、 -. "A kind of improved lu tewei preparation process (by machine translation)". . . Retrieved 2019/02/13.
• 2、 Ziegler, Robert E.,Desai, Bimbisar K.,Jee, Jo-Ann,Gupton, B. Frank,Roper, Thomas D.,Jamison, Timothy F.. "7-Step Flow Synthesis of the HIV Integrase Inhibitor Dolutegravir". . p. 7181 - 7185. Retrieved 2018/06/15.