1335210-35-9|(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| Ambeed

Structure of 1335210-35-9

*Storage: {[sel_prStorage]}

*Shipping: {[sel_prShipping]}

4.5 *For Research Use Only !

{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]} Purity: {[proInfo.pro_purity]}

Change View

Size	Price	VIP Price	US Stock	Global Stock	In Stock
{[ item.pr_size ]}		Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}

US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days

{[ item.pr_size ]}

In Stock

- +

Please Login or Create an Account to: See VIP prices and availability

US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks

Quality Control of [ 1335210-35-9 ] Purity: 97% SDS Specification

COA

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

NMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

CNMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

HPLC

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

LC-MS

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

1-2 Day Shipping
High Quality
Technical Support

Product Details of [ 1335210-35-9 ]

CAS No. :	1335210-35-9
Formula :	C₂₁H₂₁F₂N₃O₅
M.W :	433.41
SMILES Code :	O=C(C1=CN2C(C(N3[C@](OCC[C@H]3C)([H])C2)=O)=C(OC)C1=O)NCC4=CC=C(F)C=C4F
MDL No. :	MFCD29059073
InChI Key :	MOSMLVZNRGURDI-BZNIZROVSA-N
Pubchem ID :	53469002

Safety of [ 1335210-35-9 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Computational Chemistry of [ 1335210-35-9 ] Show Less

Physicochemical Properties

Num. heavy atoms	31
Num. arom. heavy atoms	12
Fraction Csp3	0.38
Num. rotatable bonds	5
Num. H-bond acceptors	7.0
Num. H-bond donors	1.0
Molar Refractivity	108.95
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	89.87 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.5
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	2.22
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	1.96
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	0.87
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	2.39
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.99

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-3.88
Solubility	0.0568 mg/ml ; 0.000131 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-3.74
Solubility	0.0785 mg/ml ; 0.000181 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-5.16
Solubility	0.00301 mg/ml ; 0.00000693 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Moderately soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	No
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	Yes
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	No
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	Yes
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	Yes
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-7.37 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	0.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	0.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	4.32

Application In Synthesis of [ 1335210-35-9 ]

* 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 [ 1335210-35-9 ]

[ 1335210-35-9 ] Synthesis Path-Downstream 1~35

1
[ 1335210-35-9 ]
dolutegravir [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With lithium bromide; In tetrahydrofuran; methanol; isopropyl alcohol; at 60℃; for 6h;Large scale;	(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 (3.9 Kg, 9.0 moles) was demethylated with Lithium bromide (1.56 kg, 18.0 moles) in Methanol / IP AJ THF at temperature of 60C. After 6 hrs, the reaction mass was cooled to RT, treated with 10% Aq. HC1 solution and extracted in dichloromethane. The organic layer was concentrated & solid was isolated in isopropyl alcohol to yield Compound (I). (0277) HPLC purity : 99.0% (0278) Yield : 92.0%. (0279) Chiral Purity: 99.0%
43%	With magnesium bromide; In acetonitrile; at 50℃; for 30h;	Compound 7 (480 mg, 1.11 mmol) was dissolved in 9.12 ml of acetonitrile and anhydrous MgBr2 (470 mg, 2.55 mmol) was added.The mixture was placed in a 50 C oil bath and stirred for 30 h, and the reaction mixture was a white suspension.The reaction was quenched by adding 11.4 ml of hydrochloric acid, and the reaction solution was clarified, and the reaction solution was diluted with CH 2 Cl 2 and the pH was adjusted to about 1,The organic phase was separated, and the aqueous layer was extracted twice again with 11.4 ml of CH2Cl2.Add 3 ml AcOEt to dissolve, suction filtration, wash with a small amount of ethyl acetate.Drying to obtain 0.37 g of a colorless solid product of Compound I;The crude product was recrystallized from ethyl acetate and ethanol to give the dolutegravir I 0.18g(Rf = 0.46, TLC developer: CH2Cl2 / MeOH = 40/1 + 0.5% HOAc),As a white solid,The yield was 43%; the HPLC purity was 98.5%.
1.5 g	With lithium bromide; In isopropyl alcohol; at 70 - 80℃; for 15h;	(4R, 12aS)-N-(2,4-difluorobenzyl)-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-carboxamide (XVIII) (2 g, 0.0046 moles) was suspended in isopropyl alcohol (20 ml) and lithium bromide (0.8 g, 0.00924 moles) was added and stirred at 70-80C for 15 h to complete the reaction. After completion of reaction the reaction mass was acidified with 5N aqueous hydrochloric acid (5 ml) and concentrated. DM Water (20 ml) was added to the concentrated mass and stirred at 25-30C to crystallize the product. The product was filtered, washed with DM Water and dried to yield Dolutegravir (I) ( 1.5 g, HPLC purity: 97.93%).

67 g		Anhydrous MgBr2 (202.1 g) was added to a solution of (4R,12aS)-N-(2,4-difluorobenzyl)-7- methyoxy-4-methyl-6, 8-dioxo-3, 4,6,8, 12, 12a-hexahydro-2H-pyrido[ 1 ' ,2' :4,5]pyrazino[2, 1- b][l,3]oxazine-9-carboximide (formula la, 120 g) in acetonitrile (480 mL). The reaction mixture was heated to 50-52 C for 8 hours. The reaction mixture was then cooled to 25-35 C and the acetonitrile layer was siphoned out. Methylene dichloride (1800 mL) and dilute HC1 solution (240 mL HC1 + 1056 mL water) was added to the residual mass, and the solution was stirred. The organic layer was separated off, washed with water, and the solvent was distilled off under reduced pressure. The residue was crystallized from methanol to obtain dolutegravir (67 g)-
	With magnesium bromide hexahydrate; at 80℃; for 2h;	To the reaction flask was charged acetonitrile (700g) andCompound C (90 g, 0.228 mol);Stirring heated to 50 ,Add acetic acid (13.7g, 1eq);Warmed to 60 ~ 65 ,R-3-Amino-1-butanol (22.3 g, 1.1 eq) was added dropwiseAcetonitrile (100 g);The reaction was stirred for 15 hours to liquid phase compound (D)After HPLC purity 98.0%, magnesium bromide hexahydrate (199.7 g, 3 eq)Heated to 80 , stirred for 2h;After the reaction is completed,Into 3% hydrochloric acid (830g) and methylene chloride (1200g);Layered, the water layer into dichloromethane (600g; layered, the combined organic layer was concentrated to dryness, into ethanol,Concentrate again to dryness to give duloxeuma (90.9% yield).

References: [1]Patent: WO2019/159199,2019,A1 .Location in patent: Page/Page column 34; 35; 36; 38; 39.
[2]Angewandte Chemie - International Edition,2018,vol. 57,p. 7181 - 7185.
Angew. Chem.,2018,vol. 130,p. 7299 - 7303,5.
[3]Patent: CN109293675,2019,A .Location in patent: Paragraph 0004; 0037-0038.
[4]Patent: WO2014/128545,2014,A2 .Location in patent: Page/Page column 22-23.
[5]Patent: WO2016/125192,2016,A2 .Location in patent: Page/Page column 30; 34.
[6]Patent: CN106565747,2017,A .Location in patent: Paragraph 0035-0037; 0044-0045.

2
[ 127958-23-0 ]
[ 1335210-35-9 ]

References: [1]Patent: WO2015/19310,2015,A1 .
[2]Patent: WO2016/125192,2016,A2 .
[3]Patent: WO2016/125192,2016,A2 .
[4]Patent: CN109293675,2019,A .

3
[ 1335210-26-8 ]
[ 1335210-35-9 ]

References: [1]Patent: WO2015/19310,2015,A1 .
[2]Patent: CN109293675,2019,A .

4
C₁₃H₁₆ClNO₇ [ No CAS ]
[ 1335210-35-9 ]

References: [1]Patent: WO2015/19310,2015,A1 .

5
C₁₀H₁₆ClNO₅ [ No CAS ]
[ 1335210-35-9 ]

References: [1]Patent: WO2015/19310,2015,A1 .

6
C₈H₁₂ClNO₃ [ No CAS ]
[ 1335210-35-9 ]

References: [1]Patent: WO2015/19310,2015,A1 .
[2]Patent: WO2015/19310,2015,A1 .

7
1-(2,2-dimethoxy-ethyl)-3-methoxy-4-oxo-1,4-dihydro-pyridine-2,5-dicarboxylic acid dimethyl ester [ No CAS ]
[ 1335210-35-9 ]

References: [1]Patent: WO2015/19310,2015,A1 .
[2]Patent: WO2016/125192,2016,A2 .
[3]Patent: CN109293675,2019,A .
[4]Patent: WO2019/159199,2019,A1 .

8
1-(2,2-dimethoxyethyl)-3-methoxy-4-oxo-1,4-dihydro-pyridine-2,5-dicarboxylic acid dimethyl ester boron complex [ No CAS ]
[ 1335210-35-9 ]

References: [1]Patent: WO2015/19310,2015,A1 .

9
[ 1335210-34-8 ]
[ 72235-52-0 ]
[ 1335210-35-9 ]

Yield	Reaction Conditions	Operation 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%.

References: [1]Patent: CN109293675,2019,A .Location in patent: Paragraph 0004; 0035-0036.
[2]Patent: WO2015/19310,2015,A1 .Location in patent: Page/Page column 16; 17.
[3]Patent: WO2019/159199,2019,A1 .Location in patent: Page/Page column 34; 37; 38.

10
C₁₆H₁₈BNO₁₁ [ No CAS ]
[ 1335210-35-9 ]

References: [1]Patent: WO2015/19310,2015,A1 .

11
[ 41051-15-4 ]
[ 1335210-35-9 ]

References: [1]Patent: WO2015/19310,2015,A1 .
[2]Patent: WO2016/125192,2016,A2 .
[3]Patent: WO2016/125192,2016,A2 .
[4]Patent: WO2016/125192,2016,A2 .
[5]Patent: CN109293675,2019,A .
[6]Patent: WO2019/159199,2019,A1 .

12
C₁₈H₂₁BN₂O₁₀ [ No CAS ]
[ 1335210-35-9 ]

References: [1]Patent: WO2015/19310,2015,A1 .

13
[ 1335210-35-9 ]
[ 1051375-19-9 ]

Yield	Reaction Conditions	Operation in experiment
90%	With methanol; sodium hydroxide; In butan-1-ol; at 100℃;Flow reactor; Large scale;	A solution of (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) (3.9 Kg, 9.0 moles) in n-butanol was mixed with a solution of sodium hydroxide (3.6 kg, 90.0 moles) in methanol in Tube Flow Reactor at l00C with residence time of 20 mins to yield Sodium salt of Compound (I). (0260) HPLC purity : 99.0% (0261) Yield : 90.0%. (0262) Particle size :d90 NMT 15 pm.
90 g		(3S,11aR)-N-[(2,4-difluorophenyl)methyl]-3-methyl-6-(methyloxy)-5,7-dioxo- 2,3,5, 7, 11,11 a-hexahydro[ 1 ,3 ]oxazolo[3 ,2-a]pyrido[ 1 ,2-d]pyrazine-8- carboxamide (100 gm) was dissolved in acetonitrile (1000 mL) and magnesium bromide hexahydrate (161 gm) was added. The mixture was heated to 80C for 2 hours, quenched with HC1 and then extracted with methylene dichloride. Methanol (1452 mL) and n-butanol (4840 mL) was added at a temperature of 27C and then the temperature of the reaction mass was raised to 77C. Stirred the reaction mass for 1 hour at the same temperature to get a clear solution. The reaction mass was cooled to a temperature of 37C and then methanolic sodium hydroxide was slowly added. Cooled the reaction mass to 25C and stirred for 20 hours. The product was filtered, washed with n-butanol and dried under vacuum (90 gm).

References: [1]Patent: WO2019/159199,2019,A1 .Location in patent: Page/Page column 35; 36; 37; 38.
[2]Patent: WO2015/19310,2015,A1 .Location in patent: Page/Page column 17.
[3]Patent: WO2016/125192,2016,A2 .

14
dimethyl-1-allyl-3-methoxy-4-oxo-1,4-dihydropyridine-2,5-dicarboxylate [ No CAS ]
[ 1335210-35-9 ]

References: [1]Patent: WO2016/125192,2016,A2 .
[2]Patent: WO2016/125192,2016,A2 .

15
C₁₆H₁₈BNO₁₀ [ No CAS ]
[ 1335210-35-9 ]

References: [1]Patent: WO2016/125192,2016,A2 .

16
1-allyl-5-methoxy-6-(methoxycarbonyl)-4-oxo-1,4-dihydropyridine-3-carboxylic acid [ No CAS ]
[ 1335210-35-9 ]

References: [1]Patent: WO2016/125192,2016,A2 .

17
methyl 1-allyl-5-(2,4-difluorobenzylcarbamoyl)-3-methoxy-4-oxo-1,4-dihydropyridine-2-carboxylate [ No CAS ]
[ 1335210-35-9 ]

References: [1]Patent: WO2016/125192,2016,A2 .

18
[ 61477-40-5 ]
methyl 5-(2,4-difluorobenzylcarbamoyl)-3-methoxy-4-oxo-1-(2-oxoethyl)-1,4-dihydropyridine-2-carboxylate [ No CAS ]
[ 1335210-35-9 ]

Yield	Reaction Conditions	Operation in experiment
66 g	With acetic acid; In acetonitrile; at 70℃; for 12h;Inert atmosphere;	Methyl l-allyl-5-(2,4-difluorobenzylcarbamoyl)-3-methoxy-4-oxo-l,4-dihydro pyridine-2- carboxylate (formula 3a, 100 g) in 5% aqueous tetrahydrofuran (1500 mL) was added to a three- neck round bottom flask. Ozone gas was then passed through the reaction mixture for 4 hours while maintaining the temperature at -20 to -10 C. The reaction mixture was then purged with nitrogen gas, the temperature was raised to 25-35 C, and water (1000 mL) and ethylacetate (1000 mL) were added. The reaction mixture was stirred and the organic layer was separated and washed with 5% sodium dithionite solution (300 mL). The organic layer was then washed with 10% NaCl solution (500 mL). The solvent was distilled off under reduced pressure residual mass obtained to this stripping with acetonitrile (100 mL). Residual mass was added into acetonitrile (400 mL) and acetic acid (30.61 g), the temperature was raised to 70 C, and a solution of 3R-aminobutanol (27.24 g) and acetonitrile (100 mL) was added. The solution was further stirred for 12 hours. The reaction mixture was cooled to 25-35 C, water (500 mL) was added, and the pH was adjusted to 8-9 using 10% NaOH solution (175 mL). The product was then extracted by adding methylene dichloride (500 mL) and the organic layer was separated out. Methylene dichloride (300 mL) was added to the aqueous layer and the layers were separated. The combined organic layers were washed with water (400 mL). The solvent was completely distilled off under reduced pressure to obtained a thick residue which was stripped with isopropyl alcohol (100 mL) and recrystallized from isopropyl alcohol (200 mL) and n-heptane (100 mL) to obtain (4R,12aS)-N-(2,4-difluorobenzyl)-7-methyoxy-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-carboximide (formula la, 66 g).
	With acetic acid; In acetonitrile; at 50 - 65℃; for 15h;	To the reaction flask was charged acetonitrile (700g) andCompound C (90 g, 0.228 mol);Stirring heated to 50 ,Add acetic acid (13.7g, 1eq);Warmed to 60 ~ 65 ,R-3-Amino-1-butanol (22.3 g, 1.1 eq) was added dropwiseAcetonitrile (100 g);The reaction was stirred for 15 hours to liquid phase compound (D)After HPLC purity 98.0%, magnesium bromide hexahydrate (199.7 g, 3 eq)Heated to 80 , stirred for 2h;After the reaction is completed,Into 3% hydrochloric acid (830g) and methylene chloride (1200g);Layered, the water layer into dichloromethane (600g; layered, the combined organic layer was concentrated to dryness, into ethanol,Concentrate again to dryness to give duloxeuma (90.9% yield).

References: [1]Patent: WO2016/125192,2016,A2 .Location in patent: Page/Page column 29-30.
[2]Patent: CN106565747,2017,A .Location in patent: Paragraph 0035-0037; 0044-0045.

19
methyl (E)-2-(((2,2-dimethoxyethyl)amino)methylene)-4-methoxy-3-oxobutanoate [ No CAS ]
[ 1335210-35-9 ]

References: [1]Patent: WO2016/125192,2016,A2 .

20
1-(2,2-dimethoxyethyl)-3-methoxy-4-oxo-1,4-dihydropyridine-2,5-dicarboxylate boron [ No CAS ]
[ 1335210-35-9 ]

References: [1]Patent: WO2016/125192,2016,A2 .

21
[ 1335210-23-5 ]
[ 1335210-35-9 ]

References: [1]Patent: WO2016/125192,2016,A2 .
[2]Patent: CN106565747,2017,A .
[3]Patent: CN109293675,2019,A .
[4]Patent: WO2019/159199,2019,A1 .

22
methyl-5-carbamoyl-1-(2,2-dimethoxyethyl)-3-methoxy-4-oxo-1,4-dihydropyridine-2-carboxylate [ No CAS ]
[ 1335210-35-9 ]

References: [1]Patent: WO2016/125192,2016,A2 .

23
[ 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 [ No CAS ]
[ 1335210-35-9 ]

Yield	Reaction Conditions	Operation in experiment
600 mg	With triethylsilane; trifluoroacetic acid; In toluene;Reflux;	Triethylsilane (3.4 g) was added to a mixture of (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-carboxamide (formula 9, 3 g) and 2,4-diflurobenzaldehyde (4.2 g) in toluene (33 mL). Trifluoroacetic acid (3.25 g) was then added. The reaction mixture was heated to reflux and maintained until complete conversion of the starting material, after which the mass was cooled to 30 C. Water (9 mL) was added and the pH was adjusted to 7-7.5 using 5% aqueous sodium bicarbonate solution. The aqueous layer was extracted with ethyl acetate (2 x 15 mL), washed with saturated aqueous sodium chloride solution, and distilled under reduced pressure to obtain a residue which was heated with isopropyl alcohol (6 mL) and n-heptane (25 mL) to 60 C and cooled to give (4R,12aS)-N- (2,4-difluorobenzyl)-7-methyloxy-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-carboximide (formula la, 600 mg).

References: [1]Patent: WO2016/125192,2016,A2 .Location in patent: Page/Page column 33.

24
C₁₀H₁₅NO₄ [ No CAS ]
[ 1335210-35-9 ]

References: [1]Patent: WO2016/125192,2016,A2 .
[2]Patent: WO2016/125192,2016,A2 .

25
[ 1616340-68-1 ]
[ 1335210-35-9 ]

References: [1]Patent: CN106565747,2017,A .

26
[ 72235-52-0 ]
[ 1335210-35-9 ]

References: [1]Patent: CN106565747,2017,A .

27
[ 1616340-68-1 ]
[ 1335210-35-9 ]
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 [ No CAS ]
(R)-N-(2,4-difluorobenzyl)-2-(4-hydroxybutan-2-yl)-9-methoxy-1,8-dioxo-1,8-dihydro-2H-pyrido[1,2-a]pyrazine-7-carboxamide [ No CAS ]

References: [1]Angewandte Chemie - International Edition,2018,vol. 57,p. 7181 - 7185.
Angew. Chem.,2018,vol. 130,p. 7299 - 7303,5.

28
[ 61477-40-5 ]
[ 1616340-68-1 ]
[ 1335210-35-9 ]
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 [ No CAS ]
(R)-N-(2,4-difluorobenzyl)-2-(4-hydroxybutan-2-yl)-9-methoxy-1,8-dioxo-1,8-dihydro-2H-pyrido[1,2-a]pyrazine-7-carboxamide [ No CAS ]

References: [1]Angewandte Chemie - International Edition,2018,vol. 57,p. 7181 - 7185.
Angew. Chem.,2018,vol. 130,p. 7299 - 7303,5.

29
[ 61477-40-5 ]
methyl 5-(2,4-difluorobenzylcarbamoyl)-3-methoxy-4-oxo-1-(2-oxoethyl)-1,4-dihydropyridine-2-carboxylate [ No CAS ]
[ 1335210-35-9 ]
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 [ No CAS ]
(R)-N-(2,4-difluorobenzyl)-2-(4-hydroxybutan-2-yl)-9-methoxy-1,8-dioxo-1,8-dihydro-2H-pyrido[1,2-a]pyrazine-7-carboxamide [ No CAS ]

References: [1]Angewandte Chemie - International Edition,2018,vol. 57,p. 7181 - 7185.
Angew. Chem.,2018,vol. 130,p. 7299 - 7303,5.

30
[ 41051-15-4 ]
[ 1335210-35-9 ]
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 [ No CAS ]
(R)-N-(2,4-difluorobenzyl)-2-(4-hydroxybutan-2-yl)-9-methoxy-1,8-dioxo-1,8-dihydro-2H-pyrido[1,2-a]pyrazine-7-carboxamide [ No CAS ]

References: [1]Angewandte Chemie - International Edition,2018,vol. 57,p. 7181 - 7185.
Angew. Chem.,2018,vol. 130,p. 7299 - 7303,5.
[2]Angewandte Chemie - International Edition,2018,vol. 57,p. 7181 - 7185.
Angew. Chem.,2018,vol. 130,p. 7299 - 7303,5.

31
[ 127958-23-0 ]
[ 1335210-35-9 ]
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 [ No CAS ]
(R)-N-(2,4-difluorobenzyl)-2-(4-hydroxybutan-2-yl)-9-methoxy-1,8-dioxo-1,8-dihydro-2H-pyrido[1,2-a]pyrazine-7-carboxamide [ No CAS ]

32
methyl (E)-2-(((2,2-dimethoxyethyl)amino)methylene)-4-methoxy-3-oxobutanoate [ No CAS ]
[ 1335210-35-9 ]
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 [ No CAS ]
(R)-N-(2,4-difluorobenzyl)-2-(4-hydroxybutan-2-yl)-9-methoxy-1,8-dioxo-1,8-dihydro-2H-pyrido[1,2-a]pyrazine-7-carboxamide [ No CAS ]

33
1-(2,2-dimethoxy-ethyl)-3-methoxy-4-oxo-1,4-dihydro-pyridine-2,5-dicarboxylic acid dimethyl ester [ No CAS ]
[ 1335210-35-9 ]
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 [ No CAS ]
(R)-N-(2,4-difluorobenzyl)-2-(4-hydroxybutan-2-yl)-9-methoxy-1,8-dioxo-1,8-dihydro-2H-pyrido[1,2-a]pyrazine-7-carboxamide [ No CAS ]

34
5-methoxy-6-(methoxycarbonyl)-4-oxo-1-(2-oxoethyl)-1,4-dihydropyridine-3-carboxylic acid [ No CAS ]
[ 1335210-35-9 ]

References: [1]Patent: CN109293675,2019,A .
[2]Patent: WO2019/159199,2019,A1 .

35
methyl (Z)-2-((dimethylamino)methylene)-4-methoxy-3-oxobutanoate [ No CAS ]
[ 1335210-35-9 ]

References: [1]Patent: WO2019/159199,2019,A1 .

Historical Records

Technical Information

• Acyl Group Substitution • Alkyl Halide Occurrence • Baeyer-Villiger Oxidation • Barbier Coupling Reaction • Baylis-Hillman Reaction • Bucherer-Bergs Reaction • Buchwald-Hartwig C-N Bond and C-O Bond Formation Reactions • Chan-Lam Coupling Reaction • Clemmensen Reduction • Complex Metal Hydride Reductions • Corey-Bakshi-Shibata (CBS) Reduction • Corey-Chaykovsky Reaction • Fischer Indole Synthesis • Grignard Reaction • Henry Nitroaldol Reaction • Horner-Wadsworth-Emmons Reaction • Hydride Reductions • Lawesson's Reagent • Leuckart-Wallach Reaction • Mannich Reaction • McMurry Coupling • Meerwein-Ponndorf-Verley Reduction • Nomenclature of Ethers • Passerini Reaction • Paternò-Büchi Reaction • Petasis Reaction • Peterson Olefination • Pictet-Spengler Tetrahydroisoquinoline Synthesis • Preparation of Aldehydes and Ketones • Preparation of Amines • Preparation of Ethers • Prins Reaction • Reactions of Aldehydes and Ketones • Reactions of Amines • Reactions of Benzene and Substituted Benzenes • Reactions of Ethers • Reformatsky Reaction • Robinson Annulation • Schlosser Modification of the Wittig Reaction • Schmidt Reaction • Specialized Acylation Reagents-Carbodiimides and Related Reagents • Specialized Acylation Reagents-Ketenes • Specialized Acylation Reagents-Vilsmeier Reagent • Stobbe Condensation • Tebbe Olefination • Ugi Reaction • Wittig Reaction • Wolff-Kishner Reduction

Related Functional Groups of
[ 1335210-35-9 ]

Fluorinated Building Blocks

A191959 [1206102-11-5]

(4R,12aS)-7-(Benzyloxy)-N-(2,4-difluorobenzyl)-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

Similarity: 0.97

A104063 [190595-65-4]

(3R,4S)-4-(4-(Benzyloxy)phenyl)-1-(4-fluorophenyl)-3-(3-(4-fluorophenyl)-3-oxopropyl)azetidin-2-one

Similarity: 0.62

A294611 [177325-13-2]

(S)-9-Fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-3,7-dihydro-2H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid hydrochloride

Similarity: 0.62

A115482 [182868-72-0]

1-Cyclopropyl-8-ethoxy-6-fluoro-7-(3-methylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

Similarity: 0.60

A264523 [226578-51-4]

(S)-9-Fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid methanesulfonic acid salt

Similarity: 0.60

Aryls

A191959 [1206102-11-5]

(4R,12aS)-7-(Benzyloxy)-N-(2,4-difluorobenzyl)-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

Similarity: 0.97

A104063 [190595-65-4]

(3R,4S)-4-(4-(Benzyloxy)phenyl)-1-(4-fluorophenyl)-3-(3-(4-fluorophenyl)-3-oxopropyl)azetidin-2-one

Similarity: 0.62

A115873 [163222-32-0]

(3R,4S)-4-(4-(Benzyloxy)phenyl)-1-(4-fluorophenyl)-3-((S)-3-(4-fluorophenyl)-3-hydroxypropyl)azetidin-2-one

Similarity: 0.59

A347543 [204589-82-2]

3-((2S,3R)-2-(4-(Benzyloxy)phenyl)-1-(4-fluorophenyl)-4-oxoazetidin-3-yl)propanoic acid

Similarity: 0.59

A136268 [832720-36-2]

Sodium (R)-4-((2-(5-(2-fluoro-3-methoxyphenyl)-3-(2-fluoro-6-(trifluoromethyl)benzyl)-4-methyl-2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl)-1-phenylethyl)amino)butanoate

Similarity: 0.58

Ethers

A191959 [1206102-11-5]

(4R,12aS)-7-(Benzyloxy)-N-(2,4-difluorobenzyl)-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

Similarity: 0.97

A279346 [1335210-24-6]

(3S,11AR)-6-methoxy-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydrooxazolo[3,2-a]pyrido[1,2-d]pyrazine-8-carboxylic acid

Similarity: 0.74

A104063 [190595-65-4]

(3R,4S)-4-(4-(Benzyloxy)phenyl)-1-(4-fluorophenyl)-3-(3-(4-fluorophenyl)-3-oxopropyl)azetidin-2-one

Similarity: 0.62

A115482 [182868-72-0]

1-Cyclopropyl-8-ethoxy-6-fluoro-7-(3-methylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

Similarity: 0.60

A347543 [204589-82-2]

3-((2S,3R)-2-(4-(Benzyloxy)phenyl)-1-(4-fluorophenyl)-4-oxoazetidin-3-yl)propanoic acid

Similarity: 0.59

Amides

A191959 [1206102-11-5]

(4R,12aS)-7-(Benzyloxy)-N-(2,4-difluorobenzyl)-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

Similarity: 0.97

A279346 [1335210-24-6]

(3S,11AR)-6-methoxy-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydrooxazolo[3,2-a]pyrido[1,2-d]pyrazine-8-carboxylic acid

Similarity: 0.74

A104063 [190595-65-4]

(3R,4S)-4-(4-(Benzyloxy)phenyl)-1-(4-fluorophenyl)-3-(3-(4-fluorophenyl)-3-oxopropyl)azetidin-2-one

Similarity: 0.62

A115873 [163222-32-0]

(3R,4S)-4-(4-(Benzyloxy)phenyl)-1-(4-fluorophenyl)-3-((S)-3-(4-fluorophenyl)-3-hydroxypropyl)azetidin-2-one

Similarity: 0.59

A347543 [204589-82-2]

3-((2S,3R)-2-(4-(Benzyloxy)phenyl)-1-(4-fluorophenyl)-4-oxoazetidin-3-yl)propanoic acid

Similarity: 0.59

Ketones

A191959 [1206102-11-5]

(4R,12aS)-7-(Benzyloxy)-N-(2,4-difluorobenzyl)-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

Similarity: 0.97

A279346 [1335210-24-6]

(3S,11AR)-6-methoxy-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydrooxazolo[3,2-a]pyrido[1,2-d]pyrazine-8-carboxylic acid

Similarity: 0.74

A104063 [190595-65-4]

(3R,4S)-4-(4-(Benzyloxy)phenyl)-1-(4-fluorophenyl)-3-(3-(4-fluorophenyl)-3-oxopropyl)azetidin-2-one

Similarity: 0.62

A294611 [177325-13-2]

(S)-9-Fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-3,7-dihydro-2H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid hydrochloride

Similarity: 0.62

A115482 [182868-72-0]

1-Cyclopropyl-8-ethoxy-6-fluoro-7-(3-methylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

Similarity: 0.60

Amines

A191959 [1206102-11-5]

(4R,12aS)-7-(Benzyloxy)-N-(2,4-difluorobenzyl)-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

Similarity: 0.97

A136268 [832720-36-2]

Sodium (R)-4-((2-(5-(2-fluoro-3-methoxyphenyl)-3-(2-fluoro-6-(trifluoromethyl)benzyl)-4-methyl-2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl)-1-phenylethyl)amino)butanoate

Similarity: 0.58

A225196 [1801787-56-3]

N-(4-(4-Methylpiperazin-1-yl)-3'-(morpholinomethyl)-[1,1'-biphenyl]-3-yl)-6-oxo-4-(trifluoromethyl)-1,6-dihydropyridine-3-carboxamide

Similarity: 0.57

A124138 [452105-23-6]

(S,Z)-5-((5-Fluoro-2-oxoindolin-3-ylidene)methyl)-N-(2-hydroxy-3-morpholinopropyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide

Similarity: 0.56

A136576 [1253799-29-9]

Phenyl 2-(benzyloxy)-3-(dibenzylamino)-5-fluoro-6-methylbenzoate

Similarity: 0.55

Related Parent Nucleus of
[ 1335210-35-9 ]

Other Aromatic Heterocycles

A191959 [1206102-11-5]

(4R,12aS)-7-(Benzyloxy)-N-(2,4-difluorobenzyl)-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

Similarity: 0.97

A279346 [1335210-24-6]

(3S,11AR)-6-methoxy-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydrooxazolo[3,2-a]pyrido[1,2-d]pyrazine-8-carboxylic acid

Similarity: 0.74

A294611 [177325-13-2]

(S)-9-Fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-3,7-dihydro-2H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid hydrochloride

Similarity: 0.62

A264523 [226578-51-4]

(S)-9-Fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid methanesulfonic acid salt

Similarity: 0.60

A150088 [82419-35-0]

9,10-Difluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid

Similarity: 0.54

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

{[proInfo.proName]}

CAS No.: 1335210-35-9

{[proInfo.proName]}

CAS No.: 1335210-35-9

Alternative Products

Product Details of [ 1335210-35-9 ]

Safety of [ 1335210-35-9 ]

Computational Chemistry of [ 1335210-35-9 ] Show Less

Physicochemical Properties

Lipophilicity

Water Solubility

Pharmacokinetics

Druglikeness

Medicinal Chemistry

Application In Synthesis of [ 1335210-35-9 ]

[ 1335210-35-9 ] Synthesis Path-Downstream 1~35

Related Products

Historical Records

Technical Information

Categories

Related Functional Groups of [ 1335210-35-9 ]

Fluorinated Building Blocks

Aryls

Ethers

Amides

Ketones

Amines

Related Parent Nucleus of [ 1335210-35-9 ]

Other Aromatic Heterocycles

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Molarity Calculator

Total Compounds Calculator

Dissolution Calculator

Related Functional Groups of
[ 1335210-35-9 ]

Related Parent Nucleus of
[ 1335210-35-9 ]