Home Cart 0 Sign in  

[ CAS No. 1335210-34-8 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
Chemical Structure| 1335210-34-8
Chemical Structure| 1335210-34-8
Structure of 1335210-34-8 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 1335210-34-8 ]

Related Doc. of [ 1335210-34-8 ]

Alternatived Products of [ 1335210-34-8 ]

Product Details of [ 1335210-34-8 ]

CAS No. :1335210-34-8 MDL No. :MFCD28978321
Formula : C14H16N2O6 Boiling Point : -
Linear Structure Formula :- InChI Key :-
M.W : 308.29 Pubchem ID :-
Synonyms :

Safety of [ 1335210-34-8 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313 UN#:N/A
Hazard Statements:H315-H319 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 1335210-34-8 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 1335210-34-8 ]

[ 1335210-34-8 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 1335210-34-8 ]
  • [ 1186663-18-2 ]
  • [ 1656286-80-4 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; HATU In dichloromethane at 20℃; for 0.5h; 5.1 Example 5 Preparation of Compound 5 (4R., 12aS)-N-(l-(2,4-difluoropheny].)cyclopropyl)-7-hydroxy-4-methyi-6,8-dioxo- 3,4,6,8, 12, i2a-hexahydro-2H-[l ,3]oxazino[3,2-d]pyrido[l ,2-a]pyrazine-9-carboxamide Step 1 Example 5 Preparation of Compound 5 (4R., 12aS)-N-(l-(2,4-difluoropheny].)cyclopropyl)-7-hydroxy-4-methyi-6,8-dioxo- 3,4,6,8, 12, i2a-hexahydro-2H-[l ,3]oxazino[3,2-d]pyrido[l ,2-a]pyrazine-9-carboxamide Step 1 (4R,12aS)-7-methoxy-4-methyl-6,8-dioxo-3 ,4,6,8, 12, 12a-hexahydro- 2H-[l ,3]oxazino[3,2-d]pyrido[ l ,2-a]pyrazine-9-carboxylic acid (Intermediate 5- A) was prepared in an analogous manner to (3S,l laR)-6-methoxy-3-methyl-5,7-dioxo- 2,3,5,7, 1 1 ,1 la-hexahydrooxazolo[3,2-d]pyrido[l ,2-a]pyrazine-8-carboxylic acid as described in WO201 1/1 19566, substituting (R)-3-aminobutan~l~ol for (S)-2~ aminopropan-l-ol . WO20.i l 1 19566 is incorporated herein by reference in its entirety. A suspension of Intermediate 5-A (24.8 mg, 0.080 mmol ), l-(2,4- difluoropheny].)cyclopropanamine HC1 salt (5-15, 21.9 mg, 0.107 mmol), and HATU (48 mg, 0.126 mmol) in CH2C12 (2 mL) was stirred at ambient temperature as N,N- diisopropylethyl amine (DIPEA) (0.1 mL, 0.574 mmol) was added. After 30 minutes, the reaction mixture was diluted with ethyl acetate before washing with 10% aqueous citric acid solution (xl) and saturated aqueous NaHC03 solution (xl). After the aqueous fractions were extracted with ethyl acetate (x l), the organic fractions were combined, dried (MgS04), and concentrated. The residue was purified by combiflash (.12 g column) using hexanes, ethyl acetate, and 20% methanol in ethyl acetate to obtain (4R.,12aS)-N-(l-(2,4-difluoropheny].)cyclopropyl)-7-methoxy-4-methyi-6,8-dioxo- 3,4,6,8, 12, 12a-hexahydro-2H-[ l ,3]oxazino[3,2-d]pyrido[ l ,2-a]pyrazine-9-carboxamide, Intermediate 5-C. LCMS-ESI+ i n/z): | VI - H i calculated for C. l l.. ,: >VO: 460.17; found 460.2.
  • 2
  • [ 1335210-23-5 ]
  • (R)-3-amino-1-butanol tartarate [ No CAS ]
  • [ 1335210-34-8 ]
YieldReaction ConditionsOperation in experiment
72 g Step-ii: Preparation of (4i?,12aS)-7-methoxy-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro- 2H-pyrido[ ,2';4,5]pyrazino[2,l-b] [l,3)oxazine-9-carboxyIic acid (XVII): l -[2,2-Bis(methyloxy)ethyl]-5-(methyloxy)-6-[(methyloxy)carbonyl]-4-oxo- l ,4-dihydro-3- pyridinecarboxylic acid (XV) ( lOOg; 0.3175 moles) was suspended in acetonitrile (800 ml) and heated to 80-82C. A mixture of acetic acid (95.25 g), methanesulfonic acid (9.14 g; 0.09525 moles) and acetonitrile (200 ml) were added to the slurry at 80-82C. The reaction mass was continued at 80-82C to complete the reaction. After completion of the reaction, anhydrous sodium acetate (65 g) and (R)-3 -amino- 1 -butanol tartrate salt (79.68g; 0.3334 moles) were added at 20- 25C and stirred at 60-65C to complete the reaction. The reaction mass was concentrated and acidified with I N aqueous hydrochloric acid (750 ml) and extracted with methylene chloride (1500 ml) at ice cold temperature. The organic layer was separated, concentrated, treated with hot methanol (350 ml) for 2 h, filtered, washed with methanol and dried to yield (4R, 12aS)-7-methoxy-4-methyl-6,8-dioxo-3,4,6,8, 12, 12a-hexahydro-2H- pyrido[ l ',2' :4,5]pyrazino[2, l -b][ l ,3]oxazine-9-carboxylic acid (XVII) (72 g; HPLC purity: 99.07%).
  • 4
  • [ 1335210-34-8 ]
  • [ 72235-52-0 ]
  • [ 1335210-35-9 ]
YieldReaction ConditionsOperation in experiment
78% With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In acetonitrile; at 80℃; for 5h; 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%.
85 g (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 carbonyldimidazole (78.89 gm) were suspended in acetonitrile (1000 mL). The mixture was heated to a temperature of 75C and stirred for 1 hour. The resulting solution was cooled to a temperature of 20C 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 a temperature of 40C, stirred the reaction mass for 30 minutes at a temperature of 50C and the cooled the reaction mass to 25C. The reaction mixture was maintained for 8 hours at the same temperature. The product was collected by filtration and dried under vacuum (85 gm).
With 4-methyl-morpholine; chloroformic acid ethyl ester; In dichloromethane; at 0℃;Flow reactor; Large scale; A solution of l-(2,2-dimethoxyethyl)-5-methoxy-6-(methoxycarbonyl)-4-oxo-l,4- dihydropyridine-3 -carboxylic acid (V) in acetic acid / Dimethyl carbonate ( 5.0Kg, 15.8 moles) and methane sulfonic acid (533.0 g, 5.6 moles) were introduced in micro channel reactor. After residence time of 9 mins at l30C gives 5-methoxy- 6-(methoxycarbonyl)-4-oxo- 1 -(2-oxoethyl)- 1 ,4-dihydropyridine-3 -carboxylic acid (IVa). The reaction mixture was further introduced in a Tube Flow reactor and cyclised with solution of R-3 amino butanol ( 1.97 kg, 22.2 moles) in Dimethyl carbonate at l00C at a residence time of 5.15 mins followed by quenching with Aq HC1 solution. The organic layer containing (4S,l2aR)-7-methoxy-4-methyl- 6,8-dioxo-3,4,6,8,l2,l2a-hexahydro-2H-pyrido[r,2':4,5]pyrazino[2,l- b][l,3]oxazine-9-carboxylic acid (III) was separated and introduced in a Tube Flow Reactor with a solution of N-Methyl Morpholine (2.25 Kg, 22.22 moles) and a solution of 2,4-diflurobenzylamine(3.l8 kg, 22.2 moles) in MDC solvent and reacted in presence of Ethyl chloroformate (1.73 Kg, 20.63 moles) at 0C. After a residence time of l. l5mins yields (4S,l2aR)-N-(2,4-Difluorobenzyl)-7-methoxy- 4-methyl-6,8-dioxo-3,4,6,8,l2,l2a-hexahydro-2H-pyrido[r,2':4,5]pyrazino[2,l- b][l,3]oxazine-9-carboxamide (Ila) which was isolated in IPA after acid base workup. (0250) HPLC purity: 99.0% (0251) Yield: 80.0%.
  • 5
  • [ 61477-40-5 ]
  • 5-methoxy-6-(methoxycarbonyl)-4-oxo-1-(2-oxoethyl)-1,4-dihydropyridine-3-carboxylic acid [ No CAS ]
  • [ 1335210-34-8 ]
YieldReaction ConditionsOperation in experiment
1.72 g In acetonitrile; at 60℃; for 18h; Compound 4 (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; Compound 5 was obtained.(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 compound 6 was obtained, 1.72 g.(Rf=0.42, TLC developing agent: CH2Cl2/MeOH=20/1+0.5% HOAc),The yield was 52% and the HPLC purity was 95.3%.
at 100℃;Flow reactor; Large scale; A solution of l-(2,2-dimethoxyethyl)-5-methoxy-6-(methoxycarbonyl)-4-oxo-l,4- dihydropyridine-3 -carboxylic acid (V) in acetic acid / Dimethyl carbonate ( 5.0Kg, 15.8 moles) and methane sulfonic acid (533.0 g, 5.6 moles) were introduced in micro channel reactor. After residence time of 9 mins at l30C gives 5-methoxy- 6-(methoxycarbonyl)-4-oxo- 1 -(2-oxoethyl)- 1 ,4-dihydropyridine-3 -carboxylic acid (IVa). The reaction mixture was further introduced in a Tube Flow reactor and cyclised with solution of R-3 amino butanol ( 1.97 kg, 22.2 moles) in Dimethyl carbonate at l00C at a residence time of 5.15 mins followed by quenching with Aq HC1 solution. The organic layer containing (4S,l2aR)-7-methoxy-4-methyl- 6,8-dioxo-3,4,6,8,l2,l2a-hexahydro-2H-pyrido[r,2':4,5]pyrazino[2,l- b][l,3]oxazine-9-carboxylic acid (III) was separated and introduced in a Tube Flow Reactor with a solution of N-Methyl Morpholine (2.25 Kg, 22.22 moles) and a solution of 2,4-diflurobenzylamine(3.l8 kg, 22.2 moles) in MDC solvent and reacted in presence of Ethyl chloroformate (1.73 Kg, 20.63 moles) at 0C. After a residence time of l. l5mins yields (4S,l2aR)-N-(2,4-Difluorobenzyl)-7-methoxy- 4-methyl-6,8-dioxo-3,4,6,8,l2,l2a-hexahydro-2H-pyrido[r,2':4,5]pyrazino[2,l- b][l,3]oxazine-9-carboxamide (Ila) which was isolated in IPA after acid base workup. (0250) HPLC purity: 99.0% (0251) Yield: 80.0%.
Same Skeleton Products
Historical Records