[ CAS No. 137281-23-3 ] {[proInfo.proName]}

Name: 137281-23-3|(S)-2-(4-(2-(2-Amino-4-oxo-4,7-dihydro-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl)benzamido)pentanedioic acid|99+%
Brand: Ambeed
SKU: A159122
Price: 6.0 USD
Availability: InStock
Rating: 93 (32 reviews)

,{[proInfo.pro_purity]}

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

DV 2D 3D

3d Animation Molecule Structure of 137281-23-3

Structure of 137281-23-3 * Storage: {[proInfo.prStorage]}

Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

For Research Only 110K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 137281-23-3 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 137281-23-3 ]

SDS Specification

Alternatived Products of [ 137281-23-3 ]

Product Details of [ 137281-23-3 ]

CAS No. :	137281-23-3	MDL No. :	MFCD19105065
Formula :	C₂₀H₂₁N₅O₆	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	WBXPDJSOTKVWSJ-ZDUSSCGKSA-N
M.W :	427.41	Pubchem ID :	135410875
Synonyms :	LY231514	Chemical Name :	(S)-2-(4-(2-(2-Amino-4-oxo-4,7-dihydro-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl)benzamido)pentanedioic acid

Calculated chemistry of [ 137281-23-3 ]

Physicochemical Properties

Num. heavy atoms :	31
Num. arom. heavy atoms :	15
Fraction Csp3 :	0.25
Num. rotatable bonds :	10
Num. H-bond acceptors :	7.0
Num. H-bond donors :	6.0
Molar Refractivity :	111.15
TPSA :	191.26 Å²

Pharmacokinetics

GI absorption :	Low
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-8.75 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.53
Log Po/w (XLOGP3) :	0.22
Log Po/w (WLOGP) :	0.67
Log Po/w (MLOGP) :	0.88
Log Po/w (SILICOS-IT) :	2.03
Consensus Log Po/w :	0.87

Druglikeness

Lipinski :	2.0
Ghose :	None
Veber :	1.0
Egan :	1.0
Muegge :	2.0
Bioavailability Score :	0.11

Water Solubility

Log S (ESOL) :	-2.33
Solubility :	2.01 mg/ml ; 0.00471 mol/l
Class :	Soluble
Log S (Ali) :	-3.8
Solubility :	0.0684 mg/ml ; 0.00016 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-4.92
Solubility :	0.00517 mg/ml ; 0.0000121 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	2.0
Synthetic accessibility :	3.38

Safety of [ 137281-23-3 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H332-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 137281-23-3 ]

* 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.

Upstream synthesis route of [ 137281-23-3 ]
Downstream synthetic route of [ 137281-23-3 ]

[ 137281-23-3 ] Synthesis Path-Upstream 1~2

1
[ 165049-28-5 ]
[ 137281-23-3 ]

Yield	Reaction Conditions	Operation in experiment
95%	Stage #1: With sodium hydroxide In water at 5 - 15℃; for 2 h; Stage #2: With hydrogenchloride In ethanol; water at 5 - 50℃; for 1 h;	Preparation of Pemetrexed diacid (Formula 2) (0081) In a reactor, 1 L of IN NaOH aqueous solution was added, and 143 g of the compound of formula 3 prepared in Example 1 was added thereto at 5-15° C. After stirring at 5-15° C. for 2 hours, the mixture was filtered (HPLC purity: 99.8percent). To the filtered solution, 2 L of EtOH was added, and 2N HCl aqueous solution was slowly added thereto dropwise at 5-15° C. to adjust pH to 3.0. The formed crystalline mixture was stirred at 40-50° C. for 1 hour and filtered at 40° C. The filtered product was washed with 2 L of purified water, and further washed with 1 L of EtOH. The filtered product as obtained was added to 4 L of EtOH/purified water (1:1, v/v), and the mixture was stirred at 40-50° C. for 1 hour, and cooled and filtered at room temperature. The filtered product was washed with 2 L of purified water, further washed with 1 L of EtOH, and dried under vacuum at 40-45° C. for 16 hours to obtain 88 g of pemetrexed diacid as white solid (Yield: 95percent, HPLC purity: 99.9percent, individual impurity content:
75.17%	Stage #1: at 2℃; for 1.5 h; Stage #2: With hydrogenchloride In water at 2 - 70℃; for 4.83333 h;	Example 6 Preparation of Pemetrexed Diacid Characterized by an X-ray Powder Diffraction Pattern Having Peaks at About 7.7, 9.2, 16.7, and 27.4 Degrees Two-Theta+/-0.2 Degrees Two-Theta 5g of N-(4-[2-(2-amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl)-L-glutamic acid diethyl ester p-toluenesulfonic Acid Salt was suspended at 2° C. in 50 mL water. 50 mL of aqueous sodium hydroxide (2M), previously cooled to 2° C., were added and the mixture was stirred for 1.5 hours at 2° C. Complete dissolution was observed. The solution was then added drop-wise, at 2° C., over 20 minutes, to a solution of 3.0 mL aqueous hydrochloric acid (37percent) in 30 mL of water and the pH was corrected from 3.9 to 4.1 with aqueous sodium hydroxide 0.1N. The resulting suspension was stirred at 2° C. for 30 min. and heated at 70° C. for two hours. After cooling to 24° C. in 2 hours, the suspension was filtered and the solid was dried in the oven at 70° C. under vacuum (1 8mbar) to yield the titled compound (75.17percent). The PXRD pattern of the dried pemetrexed diacid was measured and illustrated in FIG. 6.

Reference： [1] Patent: US2016/214987, 2016, A1, . Location in patent: Paragraph 0081
[2] Patent: US2008/45711, 2008, A1, . Location in patent: Page/Page column 11

2
[ 1118-89-4 ]
[ 137281-23-3 ]

Reference： [1] Patent: US2016/214987, 2016, A1,

[ 137281-23-3 ] Synthesis Path-Downstream 1~20

1
[ 1310-73-2 ]
[ 137281-23-3 ]
pemetrexed disodium [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; In water; acetone; at 2 - 25℃; for 10.8333h;pH 10.0;Product distribution / selectivity;	Example 14 Preparation of N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-1H-pyrrolo[2.3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid disodium salt A flask was charged with crude <strong>[137281-23-3]N-[4-[2-(2-amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid</strong> (4 g), water (28 ml) and NaOH (3 equivalents) at 25 C. Complete dissolution was obtained. The pH was corrected to 10.0 with HCl 1M and acetone (120 mL) was added drop wise over a period of 50 min. The obtained suspension was cooled to 2 C. in one hour, stirred at 2 C. for 10 hours and filtered. The solid was washed with acetone (30 mL) and dried at 40 C. under vacuum (18 mbar) for about 16 hours affording the title compound.
	With mannitol; In water;Product distribution / selectivity;	Example 13 Lyophilized N-r4-[2-(2-amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid disodium salt 5 grams of <strong>[137281-23-3]N-[4-[2-(2-amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid</strong> was dissolved in 1 L of distilled water and 11.698 ml of a 2.0 M solution of sodium hydroxide was added to the solution. Mannitol (10 g) was then added to the solution and dissolved. The solution was then filtered through a bacterial filter and dried in a freeze-drier to afford 15.5 g of title compound as a white solid.

Reference： [1]Patent: US2008/45711,2008,A1 .Location in patent: Page/Page column 12
[2]Patent: US2008/45711,2008,A1 .Location in patent: Page/Page column 12

2
pemetrexed disodium [ No CAS ]
[ 137281-23-3 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; In water; at 24 - 65℃; for 15.4167h;pH ~ 4.5;	Example 1 Preparation of Crystalline Pemetrexed Diacid Characterized by an X-ray Powder Diffraction Pattern Having Peaks at About 10.0, 10.3, 22.0 and 25.7 Degrees Two-Theta+/-0.2 Degrees Two-Theta A flask was charged with N-[4-[2-(2-amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid disodium salt (23.89 g) and water (478 ml) and stirred for 20 minutes at 24 C., to achieve complete dissolution. The pH of the resulting solution was adjusted to about 4.5 by the addition of diluted hydrochloric acid, after which abundant solid formation was observed. The resulting suspension was then heated to 65 C. for 25 minutes, was slowly cooled to 24 C. over a period of 5 hours, and was then stirred at 24 C. for 10 hours. The solid was filtered from the suspension and washed two times (2×50 ml) with water adjusted to pH 4.5 with hydrochloric acid. The wet solid was dried at 40 C. under vacuum (18 mbar) for 16.5 hours to afford the title compound as a white, fine solid (7.20 g). The X-ray powder diffraction pattern of the dry material was measured and is illustrated in FIG. 1.
		Example 2 Preparation of Crystalline Pemetrexed Diacid Characterized by an X-ray Powder Diffraction Pattern Having Peaks at About 5.7, 12.2, 17.2 and 18.4 Degrees Two-Theta+/-0.2 Degrees Two-Theta A flask was charged with N-[4-[2-(2-amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid disodium salt (12.77 g) and water (240 ml) and stirred at 24 C. to achieve complete dissolution. The pH of the resulting solution was adjusted to about 3.0 by the addition of hydrochloric acid, after which abundant solid formation was observed. The resulting suspension was then heated to 65 C. for 35 minutes, was slowly cooled to 24 C. over a period of 5 hours, and was then stirred at 24 C. for 11.5 hours. The pH of the suspension was then adjusted to about 4.5 by the addition of 2.0M sodium hydroxide, and the suspension was stirred at 24 C. for 50 minutes. The solid was filtered from the suspension and washed two times (2×50 ml) with water adjusted to pH 4.5 with hydrochloric acid. The wet solid was dried at 40 C. under vacuum (18 mbar) for 15.5 hours to afford the title compound as a white-grey solid (8.32 g). The X-ray powder diffraction pattern of the dry material was measured and is illustrated in FIG. 2.
	With hydrogenchloride; In water; acetone;pH 1.5 - 2;Heating;Product distribution / selectivity;	EXAMPLE 3The preparation of crystalline form H of pemetrexed diacid.5 g of pemetrexed disodium (dry product) was dissolved in the mixture of 75 ml of water and 70 ml of acetone. The pH value was adjusted to 1.5-2.0 with 1.5 mol/L HCl aqueous solution. The reaction mixture became clear when heating. Then, crystallization was carried out with stirring for 1 hr. The solid was filtered and washed with appropriate amount of water. The solid was dried under reduced pressure (0.0900.095 MPa) at 5560 for 15 hr to obtain 3.2 g of crystalline form H of pemetrexed diacid with water content of 8.5%.Pemetrexed diacid prepared in this example was identified as crystalline form H by X-ray diffraction.

	With hydrogenchloride; In ethanol; water;pH 1.5 - 2;Product distribution / selectivity;	5 g of pemetrexed disodium (dry product) was dissolved in 50 ml of water. Then 60 ml of ethanol was added and pH value was adjusted to 1.5-2.0 with 2mol/L HCl aqueous solution. The reaction mixture became clear when heating. Then, crystallization was carried out with stirring at room temperature for 1.5 hr. The solid was filtered and washed with appropriate amount of water (pH 4-5). Then the solid was dried at 45~50C under reduced pressure (0.085~0.90MPa) for 30 hr to obtain 2.9 g of crystalline form H of pemetrexed diacid with water content of 7.1%. For pemetrexed diacid prepared in this example, the position of diffraction peaks at 2theta are at 5.4, 6.3, 9.8, 10.6, 12.1, 16.1, 17.1, 18.1, 19.0, 19.8, 21.1, 22.6, 23.7, 24.4, 25.1, 25.8, 26.5, 27.8, 30.1, 31.1, 32.4, and 38.5(relative intensity above 10%), as measured by X-ray diffraction.
	With acetic acid; In water; at 20℃; for 1h;Inert atmosphere;	(1) N2 protection,5.0gPemetrexed disodium heptahydrate was placed in 250 mL containing 100 mL of purified waterFour-necked flask,Stir at 20 C until completely dissolved;(2) under the protection of N2,26mL volumetric concentration of 23% acetic acid aqueous solution was added to the system of step (1)The acetic acid aqueous solution within 30min drops completed;The temperature of the control system is 20 ,Stirring reaction 1h;After the reaction was filtered with suction,The filter cake was rinsed with purified water and drained twice,Each time the amount of purified water was 25mL,Then rinse the filter cake with anhydrous ethanol and drained twice,Each time the amount of anhydrous ethanol is 10mL;The resulting cake was dried under vacuum at 40 C for 12 hPemetrexed diacid;

Reference： [1]Patent: US2008/45711,2008,A1 .Location in patent: Page/Page column 10
[2]Patent: US2008/45711,2008,A1 .Location in patent: Page/Page column 10
[3]Patent: US2011/172424,2011,A1 .Location in patent: Page/Page column 4
[4]Patent: EP2351755,2011,A1 .Location in patent: Page/Page column 6
[5]Patent: CN104817563,2017,B .Location in patent: Paragraph 0029-0032; 0038-0039; 0044-0045; 0049-0050; 0055

Yield	Reaction Conditions	Operation in experiment
	In methanol; water; dimethyl sulfoxide; at 20 - 65℃; for 6h;Purification / work up;	Example 3 Preparation of Crystalline Pemetrexed Diacid Characterized by an X-ray Powder Diffraction Pattern Having Peaks At about 5.8, 12.4, 18.6 and 24.6 Degrees Two-Theta+/-0.2 Degrees Two-Theta A flask was charged with N-[4-[2-(2-amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid (98.22% HPLC purity) (10.0 g) and dimethylsulfoxide (25 ml), heated to 65 C. and stirred until complete dissolution. Methanol (37.5 ml) and water (37.5 mL) was then added drop-wise to the solution over a period of about 2.5 hours. The resulting suspension was stirred for 1 hour at 65 C. and then was cooled to 22 C. over a period of about 2.5 hours. The suspension was filtered and the isolated solid was washed with a mixture of water (50 ml) and methanol (50 mL). The solid was then dried at 40 C. under vacuum (18 mbar) for about 16 hours, to afford pemetexed diacid (7.62 g) in 99.16% purity (HPLC). A 2 g sample of the dry pemetrexed acid was slurried in 15 mL of water to form a suspension. The suspension was then heated at 50 C. for 1 h and then slowly cooled to ambient temperature and filtered. The resulting solid was dried in the oven at 80 C. under vacuum (18 mbar) for about 16 hours to afford the title compound in 99.46% purity (HPLC). The X-ray powder diffraction pattern of the dry material was measured and is illustrated in FIG. 3.

4
[ 165049-28-5 ]
[ 137281-23-3 ]

Yield	Reaction Conditions	Operation in experiment
95%		Preparation of Pemetrexed diacid (Formula 2) (0081) In a reactor, 1 L of IN NaOH aqueous solution was added, and 143 g of the compound of formula 3 prepared in Example 1 was added thereto at 5-15 C. After stirring at 5-15 C. for 2 hours, the mixture was filtered (HPLC purity: 99.8%). To the filtered solution, 2 L of EtOH was added, and 2N HCl aqueous solution was slowly added thereto dropwise at 5-15 C. to adjust pH to 3.0. The formed crystalline mixture was stirred at 40-50 C. for 1 hour and filtered at 40 C. The filtered product was washed with 2 L of purified water, and further washed with 1 L of EtOH. The filtered product as obtained was added to 4 L of EtOH/purified water (1:1, v/v), and the mixture was stirred at 40-50 C. for 1 hour, and cooled and filtered at room temperature. The filtered product was washed with 2 L of purified water, further washed with 1 L of EtOH, and dried under vacuum at 40-45 C. for 16 hours to obtain 88 g of pemetrexed diacid as white solid (Yield: 95%, HPLC purity: 99.9%, individual impurity content:
75.17%		Example 6 Preparation of Pemetrexed Diacid Characterized by an X-ray Powder Diffraction Pattern Having Peaks at About 7.7, 9.2, 16.7, and 27.4 Degrees Two-Theta+/-0.2 Degrees Two-Theta 5g of N-(4-[2-(2-amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl)-L-glutamic acid diethyl ester p-toluenesulfonic Acid Salt was suspended at 2 C. in 50 mL water. 50 mL of aqueous sodium hydroxide (2M), previously cooled to 2 C., were added and the mixture was stirred for 1.5 hours at 2 C. Complete dissolution was observed. The solution was then added drop-wise, at 2 C., over 20 minutes, to a solution of 3.0 mL aqueous hydrochloric acid (37%) in 30 mL of water and the pH was corrected from 3.9 to 4.1 with aqueous sodium hydroxide 0.1N. The resulting suspension was stirred at 2 C. for 30 min. and heated at 70 C. for two hours. After cooling to 24 C. in 2 hours, the suspension was filtered and the solid was dried in the oven at 70 C. under vacuum (1 8mbar) to yield the titled compound (75.17%). The PXRD pattern of the dried pemetrexed diacid was measured and illustrated in FIG. 6.

Reference： [1]Patent: US2016/214987,2016,A1 .Location in patent: Paragraph 0081
[2]Patent: US2008/45711,2008,A1 .Location in patent: Page/Page column 11

5
[ 67-56-1 ]
[ 137281-23-3 ]
pemetrexed disodium [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In water;	Example 8 N-(4-[2-(2-Amino-4,7-Dihydro-4-Oxo-1H-Pyrrolo[2,3-d]pyrimidin-5yl)ethyl]benzoyl)-L-Glutamic Acid Disodium Salt N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid from Example 7 was dissolved in 3.8 mL of water and 2.2 ml of 1N sodium hydroxide. The pH of the mixture was adjusted to 7.5-8.5 using dilute hydrochloric acid and 1N sodium hydroxide. The solution was heated to 70 C. and 40 mL of 3A alcohol were added. The solution was allowed to cool to room temperature during which time a thick slurry developed. The solids were filtered and washed with 4:1 ethanol:water. The solids were dried at 50 C. in a vacuum oven. 640 milligrams of the title compound were recovered as a solid. Analytical Data: 1 H NMR (300 MHz, DMSO-d6 /D2 O) delta 7.67 (d, J=7.8 Hz, 2H), 7.22 (d, J=7.8 Hz, 2H), 6.30 (s, 1H), 4.09 (m, 1H), 2.88 (m, 2H), 2.83 (m, 2H), 2.05-1.71 (m, 4H). 13 C NMR (75 MHz, DMSO-d6 /D2 O) delta 179.9, 176.9, 167.1, 160.8 152.9, 151.7, 146.7, 132.6, 129.4, 127.9, 118.7, 115.2, 99.5, 56.1, 36.8, 35.3, 30.1, 28.4.

Reference： [1]Patent: US6013828,2000,A

6
[ 137281-23-3 ]
pemetrexed disodium [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	With sodium hydroxide; In water; at 5 - 60℃; for 0.5h;	Preparation of Pemetrexed disodium salt (Formula 1) (0082) In a reactor, 1N NaOH aqueous solution was added, and 87 g of the compound of formula 2 prepared in Example 2 was added thereto at 5-15 C. After stirring for 30 minutes, the mixture was filtered. To the filtered solution, 0.5N HCl aqueous solution was slowly added dropwise to adjust the pH to 7.5-8.5. The solution was heated to 50-60 C. and 7 L of EtOH was slowly added thereto dropwise to form crystals. The formed white solid was slowly cooled to room temperature and filtered, washed with 1 L of EtOH/purified water mixture solution (4:1, v/v), and dried under vacuum at 40 C. for 21 hours to obtain 91 g of <strong>[137281-23-3]pemetrexed</strong> disodium salt as white solid (Yield: 87%, HPLC purity: >99.9%, any other single impurity content:
	With sodium formate; In water; at 20℃;pH 8;Inert atmosphere;Product distribution / selectivity;	61g of crude, wet <strong>[137281-23-3]pemetrexed</strong> (the purity is 88.5%, as measured by HPLC) (corresponding to about 20g of dry <strong>[137281-23-3]pemetrexed</strong>) was added to an aqueous sodium formate solution formed with 70g of water and 10g of sodium formate under a nitrogen atmosphere at ambient temperature, then the resulting mixture was adjusted to about pH 8 using sodium hydroxide or hydrochloric acid solution to dissolve the added <strong>[137281-23-3]pemetrexed</strong>. Then an aqueous sodium formate solution formed with 140g of water and 30g of sodium formate was added. The mixture was stirred additional 1-2h at ambient temperature and filtrated. The cake was washed with an appropriate amount of aqueous ethanol and dried to obtain 18.6g of disodium <strong>[137281-23-3]pemetrexed</strong>. The purity of the resulting disodium <strong>[137281-23-3]pemetrexed</strong> is 99.2% as measured by HPLC. If the above purification procedure was repeated once more, the purity of the resulting disodium <strong>[137281-23-3]pemetrexed</strong> is 99.8%.
		EXAMPLE 9 The preparation of <strong>[137281-23-3]pemetrexed</strong> disodium. 5 g of new crystalline form of <strong>[137281-23-3]pemetrexed</strong> diacid (dry product) prepared in the examples above was added in the 35 ml of water. The pH value was adjusted to 11-12 with 5 mol/L NaOH aqueous solution. The solution was stirred to improve dissolution, and then the pH was adjusted to 8-9 with 2 mol/L HCl. The reaction mixture was heated to 40~45, 170 ml of acetone was added. The solution was cooled to crystallize with further stirring for about 1.5 hr. The solid was filtered and washed with appropriate amount of acetone. The solid was dried under reduced pressure (0.090~0.095 MPa) at 50 for 24 hr to obtain 5.3 g of <strong>[137281-23-3]pemetrexed</strong> disodium.

5 g of new crystalline form of [137281-23-3]pemetrexed diacid (dry product) prepared in the examples above was added in the 35 ml of water. The pH value was adjusted to 11-12 with 5mol/L NaOH aqueous solution. The solution was stirred to improve dissolution, and then the pH was adjusted to 8-9 with 2mol/L HCl. The reaction mixture was heated to 40~45C, 170 ml of acetone was added. The solution was cooled to crystallize with further stirring for about 1.5 hr. The solid was filtered and washed with appropriate amount of acetone. The solid was dried under reduced pressure (0.090~0.095MPa) at 50C for 24 hr to obtain 5.3 g of [137281-23-3]pemetrexed disodium.

Reference： [1]Patent: US2016/214987,2016,A1 .Location in patent: Paragraph 0082
[2]Patent: EP2213674,2010,A1 .Location in patent: Page/Page column 9
[3]Patent: US2011/172424,2011,A1 .Location in patent: Page/Page column 5
[4]Patent: EP2351755,2011,A1 .Location in patent: Page/Page column 8

7
[ 137281-23-3 ]
potassium pemetrexed [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Example 16 purification of potassium <strong>[137281-23-3]pemetrexed</strong> 15g of crude, wet <strong>[137281-23-3]pemetrexed</strong> (the purity is 85.4%, as measured by HPLC) (corresponding to about 5g of dry <strong>[137281-23-3]pemetrexed</strong>) was added to 40g of water under a nitrogen atmosphere at ambient temperature, then the resulting mixture was adjusted to about pH11-12 using potassium hydroxide solution to obtain a clear solution. 20g of saturated potassium chloride aqueous solution was added with stirring, then the resulting mixture was adjusted to pH 8 using hydrochloric acid solution. The mixture was stirred additional 1-2h at ambient temperature and filtrated. The cake was washed with an appropriate amount of aqueous ethanol and dried to obtain 4.9g of potassium <strong>[137281-23-3]pemetrexed</strong>. The purity of the resulting potassium <strong>[137281-23-3]pemetrexed</strong> is 98.5% as measured by HPLC.

Reference： [1]Patent: EP2213674,2010,A1 .Location in patent: Page/Page column 10

8
[ 137281-23-3 ]
lithium pemetrexed [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Example 18 purification of lithium <strong>[137281-23-3]pemetrexed</strong> 30g of crude, wet <strong>[137281-23-3]pemetrexed</strong> (the purity is 85.4%, as measured by HPLC) (corresponding to about 10g of dry <strong>[137281-23-3]pemetrexed</strong>) was added to 80g of water at ambient temperature, then the resulting mixture was adjusted to about pH 11-12 using potassium hydroxide solution to obtain a clear solution. 60g of half saturated lithium bromide solution was added with stirring, then the resulting mixture was adjusted to pH 8 using lithium hydroxide or hydrochloric acid solution. The mixture was stirred additional 1-2h at ambient temperature and filtrated. The cake was washed with an appropriate amount of aqueous ethanol and dried to obtain 8.4g of lithium <strong>[137281-23-3]pemetrexed</strong>. The purity of the resulting lithium <strong>[137281-23-3]pemetrexed</strong> is 97.3% as measured by HPLC.

Reference： [1]Patent: EP2213674,2010,A1 .Location in patent: Page/Page column 10

9
C₄₅H₇₂N₉O₆⁽³⁺⁾*3I^(1-) [ No CAS ]
[ 137281-23-3 ]
C₂₀H₂₁N₅O₆*C₄₅H₇₂N₉O₆⁽³⁺⁾ [ No CAS ]

Reference： [1]European Journal of Organic Chemistry,2011,p. 6187 - 6194

10
[ 74-79-3 ]
[ 137281-23-3 ]
C₂₀H₂₁N₅O₆*2C₆H₁₄N₄O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In water; for 0.0833333h;	To 500 mg of <strong>[137281-23-3]pemetrexed</strong> diacid and 407 mg of arginine, 6 ml of water was added. The mixture was stirred until a clear solution was formed. This took approximately 5 minutes.The solvent was evaporated and the residue was dried over night at 40C under vacuum.XRPD test confirmed amorphous character of the product.TGA curve exhibits gradual mass loss of 4.738% of water between 25 and 220C.NMR confirmed the structure of bis-arginine salt (formula (2))

Reference： [1]Patent: WO2014/198338,2014,A1 .Location in patent: Page/Page column 10

11
[ 1118-89-4 ]
[ 137281-23-3 ]

Reference： [1]Patent: US2016/214987,2016,A1

12
4-(2-(2-amino-4-oxo-4,7-dihydro-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl)benzoic acid [ No CAS ]
[ 137281-23-3 ]

Reference： [1]Patent: US2016/214987,2016,A1

13
N-L-γ-glutamyl-L-glutamic acid triethyl ester [ No CAS ]
[ 137281-23-3 ]
C₃₁H₄₀N₆O₉ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.7 g		The 2g cultivates the beautiful acid, 1.3g2 - chloro - 4, 6 - dimethoxy - 1, 3, 5 - triazine are sequentially added into a 15 ml dimethyl formamide solution, dropped to 5 C, then dropwise 2 ml methyl morpholine, 25 C under stirring 1.5 hours, and then dropped to 0 C, ball point pen (2) a compound represented by the 2g, 25 C lower reaction stirred 1 hour, add 80 ml water, 150 ml dichloromethane extraction 1 time, takes organically layer anhydrous sodium sulfate drying, reduced pressure to remove the solvent to obtain 1.7g of formula (1) compound of formula. High performance liquid chromatography detection display the purity is greater than 98%.

Reference： [1]Patent: CN102796106,2016,B .Location in patent: Paragraph 0036; 0037; 0038

14
[ 140-28-3 ]
[ 137281-23-3 ]
N-[4-[2-(2-amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid-N,N'-dibenzylethylenediamine salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In acetone; at 10 - 20℃; for 4h;Inert atmosphere;	(3) under the protection of N2,Take 3.75g <strong>[137281-23-3]pemetrexed</strong> diacid obtained in step (2) into 80mL of acetoneFour-necked flask,Stir at 20 C until completely dissolved;Then in the N2 protection,At 20 C,A mixed solution of 2.2 g of N, N-dibenzylethylenediamine and 20 mL of acetone was added dropwise,Within 30min drops finished,The reaction was incubated 3h after the addition was completed;After the reaction was completed, the temperature of the reaction system was lowered to 10 C and incubated for 1h.(4) The mixture obtained in step (3) was suction filtered and the filter cake was rinsed with a 10 C. acetone solution and drained twice,Every time acetoneThe amount of 10mL;The resulting filter cake was dried under reduced pressure at 40 C for 12h,The product Pemetrexed-N, N-dibenzylethylenediamine amine salt was obtained .

Reference： [1]Patent: CN104817563,2017,B .Location in patent: Paragraph 0029; 0033; 0034; 0040-0041; 0046-0047; 0051-0052

15
[ 137281-23-3 ]
N-[4-[2-[2-amino-4,7-dihydro-4-oxo-1,5,6-trihydroxy-1H-pyrrolo[2,3-d]pyrimidin-5-yl ]ethyl]benzoyl]-L-glutamic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dihydrogen peroxide; In water; N,N-dimethyl-formamide; at 10 - 15℃; for 32h;	Pemetrexed 1.5g, added N,N-dimethylformamide 25ml, 30% aqueous solution of hydrogen peroxide 8ml, The reaction was stirred at an internal temperature of 10 to 15 C for 32 hours. A solution of <strong>[137281-23-3]pemetrexed</strong> oxide B in N,N-dimethylformamide was obtained. N-[4-[2-[2-Amino-4,7-dihydro-4-oxo-1,5,6-trihydroxy-1H-pyrrolo[2,3-d]pyrimidin-5-yl ]ethyl]benzoyl]-L-glutamic acid Synthesis of (referred to as "<strong>[137281-23-3]pemetrexed</strong> oxide B")

Reference： [1]Patent: CN102838602,2016,B .Location in patent: Paragraph 0195-0199

16
[ 137281-23-3 ]
N-[4-[2-[2-amino-4,7-dihydro-5,6-epoxy-1-hydroxy-4-oxo-1H-pyrrolo[2,3-d]pyrimidine-5-yl]ethyl]benzoyl]-L-glutamic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dihydrogen peroxide; In methanol; at 0 - 5℃; for 10h;	Pemetrexed 2g, Add 10 ml of methanol (measured as having a water content of 0.2%), Passing hydrogen peroxide gas about 0.3g, Stir the reaction at an internal temperature of 0 to 5 C for 10 hours. That is, it contains a <strong>[137281-23-3]pemetrexed</strong> oxide A methanol solution.

Reference： [1]Patent: CN102838602,2016,B .Location in patent: Paragraph 0168-0172

17
[ 56-86-0 ]
[ 137281-23-3 ]
pemetrexed glutamic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%	In methanol; at 55℃; for 1h;	Pemetrexed (42.7 g, 0.10 mol) was added to the reaction kettle.Add 1708 ml of methanol,Heated to 55 C,Stir well,Insulation at 55 C,An aqueous solution of glutamic acid (44.2 g, 0.3 mol) was added dropwise to the reaction vessel.After the completion of the dropwise addition, stirring was continued for 1 h, the temperature was lowered to room temperature, and the mixture was decanted for 2 h, centrifuged and filtered, 45-55 C, and the vacuum was -0.080 to -0.100 Mpa, and dried under vacuum for 5-6 h.Demimethrin glutamate,Molar yield 98.0%,The HPLC purity was 99.76%

Reference： [1]Patent: CN110128426,2019,A .Location in patent: Paragraph 0014-0032

18
[ 56-87-1 ]
[ 137281-23-3 ]
pemetrexed lysine salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	In ethanol; water; at 70℃; for 1h;	8.8 g of <strong>[137281-23-3]pemetrexed</strong> was added to a solution of 9 g of lysine hydrate in 41 ml of water, the solution was heated to 70 C, and added to 249 ml of ethanol, the suspension was cooled to room temperature, and the solid was dried at 50 C by filtration. 13.8 g of <strong>[137281-23-3]pemetrexed</strong> lysine salt, the molar yield was 93.3%, and the HPLC purity was 99.86%.

Reference： [1]Patent: CN110128426,2019,A .Location in patent: Paragraph 0034; 0035; 0036; 0037; 0038; 0039

19
[ 74-79-3 ]
[ 137281-23-3 ]
pemetrexed arginine salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92.9%	In ethanol; at 60℃; for 1h;	Pemetrexed (42.7g, 0.10mol) was added to the reaction vessel, 1500ml of ethanol was added, heated to 60 C, stirred evenly, kept at 60 C, and arginine (41.8 g, 0.24 mol) was added dropwise to the reaction kettle. The aqueous solution is stirred for 1 hour, cooled to room temperature, crystallization for 2 h, centrifuged and filtered, 45-55 C, vacuum degree -0.080 -0.100 Mpa vacuum drying for 5-6 h, <strong>[137281-23-3]pemetrexed</strong> arginine salt The molar yield was 92.9%, and the HPLC purity was 99.60%.

Reference： [1]Patent: CN110128426,2019,A .Location in patent: Paragraph 0040-0045

20
[ 1013921-36-2 ]
[ 137281-23-3 ]
[ 2802461-37-4 ]

Yield	Reaction Conditions	Operation in experiment
12.6%	Stage #1: (2S)-2-[4-[2-(2-amino-4-oxo-1,7-dihydropyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]amino}pentanedioic acid With 1-hydroxy-pyrrolidine-2,5-dione; N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In (methylsulfinyl)methane; N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: 3,6,9,12-tetraoxapentadec-14-yn-1-amine at 20℃; for 16h;	32 (S)-18-(4-(2-(2-amino-4-oxo-4,7-dihydro-1H-pyrrolo[2,3-d]pyrimidin-5- yl)ethyl)benzamido)-1-(1-(5-((5-(7-chloro-8-(((R)-1-(5-cyano-2-fluorophenyl)ethyl)amino)-3- fluoro-6-methyl-1,5-naphthyridin-2-yl)pyrimidin-2-yl)oxy)pentyl)-1H-1,2,3-triazol-4-yl)-15-oxo- 2,5,8,11-tetraoxa-14-azanonadecan-19-oic acid To a solution of (4-(2-(2-amino-4-oxo-4,7-dihydro-1H-pyrrolo[2,3-d]pyrimidin-5- yl)ethyl)benzoyl)-L-glutamic acid (Pemetrexed) (1, 1.0 eq, 0.500 g, 1.17 mmol) in N,N- dimethylformamide (10 mL) and dimethyl sulfoxide (10 mL), N-hydroxysuccinimide (1.1 eq, 0.148 g, 1.29 mmol), 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC.HCl) (1.1 eq, 0.247 g, 1.29 mmol) and N,N-diisopropylethylamine (3.0 eq, 0.64 mL, 3.51 mmol) were added and the reaction mixture was stirred at room temperature for 30 minutes. Then, 3,6,9,12-tetraoxapentadec- 14-yn-1-amine (1a, 1.1 eq, 0.298 g, 1.29 mmol) was added and the reaction mixture was stirred at room temperature for 16 h. After completion, the reaction mixture was directly purified by prep HPLC (20-55% acetonitrile in water with 0.1% acetic acid). Fractions containing the desired product were combined and lyophilized to dryness to afford (S)-20-(4-(2-(2-amino-4-oxo-4,7-dihydro-1H- pyrrolo[2,3-d]pyrimidin-5-yl)ethyl)benzamido)-17-oxo-4,7,10,13-tetraoxa-16-azahenicos-1-yn-21-oic acid (2) as a yellow sticky solid. Yield: 0.100 g, 12.6%; LCMS m/z 641.2 [M+1]+
12.6%	Stage #1: (2S)-2-[4-[2-(2-amino-4-oxo-1,7-dihydropyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]amino}pentanedioic acid With 1-hydroxy-pyrrolidine-2,5-dione; N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In (methylsulfinyl)methane; N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: 3,6,9,12-tetraoxapentadec-14-yn-1-amine at 20℃; for 16h;	32 (S)-18-(4-(2-(2-amino-4-oxo-4,7-dihydro-1H-pyrrolo[2,3-d]pyrimidin-5- yl)ethyl)benzamido)-1-(1-(5-((5-(7-chloro-8-(((R)-1-(5-cyano-2-fluorophenyl)ethyl)amino)-3- fluoro-6-methyl-1,5-naphthyridin-2-yl)pyrimidin-2-yl)oxy)pentyl)-1H-1,2,3-triazol-4-yl)-15-oxo- 2,5,8,11-tetraoxa-14-azanonadecan-19-oic acid To a solution of (4-(2-(2-amino-4-oxo-4,7-dihydro-1H-pyrrolo[2,3-d]pyrimidin-5- yl)ethyl)benzoyl)-L-glutamic acid (Pemetrexed) (1, 1.0 eq, 0.500 g, 1.17 mmol) in N,N- dimethylformamide (10 mL) and dimethyl sulfoxide (10 mL), N-hydroxysuccinimide (1.1 eq, 0.148 g, 1.29 mmol), 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC.HCl) (1.1 eq, 0.247 g, 1.29 mmol) and N,N-diisopropylethylamine (3.0 eq, 0.64 mL, 3.51 mmol) were added and the reaction mixture was stirred at room temperature for 30 minutes. Then, 3,6,9,12-tetraoxapentadec- 14-yn-1-amine (1a, 1.1 eq, 0.298 g, 1.29 mmol) was added and the reaction mixture was stirred at room temperature for 16 h. After completion, the reaction mixture was directly purified by prep HPLC (20-55% acetonitrile in water with 0.1% acetic acid). Fractions containing the desired product were combined and lyophilized to dryness to afford (S)-20-(4-(2-(2-amino-4-oxo-4,7-dihydro-1H- pyrrolo[2,3-d]pyrimidin-5-yl)ethyl)benzamido)-17-oxo-4,7,10,13-tetraoxa-16-azahenicos-1-yn-21-oic acid (2) as a yellow sticky solid. Yield: 0.100 g, 12.6%; LCMS m/z 641.2 [M+1]+

Reference： [1]Current Patent Assignee: LYCIA THERAPEUTICS - WO2022/150721, 2022, A1 Location in patent: Paragraph 0681-0682
[2]Current Patent Assignee: LYCIA THERAPEUTICS - WO2022/150721, 2022, A1 Location in patent: Paragraph 0681-0682

Same Skeleton Products

Related Products

Historical Records

Similar Product of
[ 137281-23-3 ]

A708744[ 357166-30-4 ]

(S)-2-(4-(2-(2-Amino-4-oxo-4,7-dihydro-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl)benzamido)pentanedioic acid, sodium salt 2.5 hydrate

Reason: Free-salt

A206176[ 150399-23-8 ]

Sodium (S)-2-(4-(2-(2-amino-4-oxo-4,7-dihydro-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl)benzamido)pentanedioate

Reason: Free-salt

Ghs Precautionary Statements

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

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
{[ item.p_purity ]}	{[ item.pr_size ]}	{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]}	{[ getRatePrice(item.pr_usd, 1,1) ]}	Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]}	{[ item.pr_usastock ]}	Inquiry -	{[ item.pr_chinastock ]}	Inquiry -

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

[ CAS No. 137281-23-3 ] {[proInfo.proName]}

Quality Control of [ 137281-23-3 ]

Related Doc. of [ 137281-23-3 ]

Product Details of [ 137281-23-3 ]

Calculated chemistry of [ 137281-23-3 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 137281-23-3 ]

Application In Synthesis of [ 137281-23-3 ]

[ 137281-23-3 ] Synthesis Path-Upstream 1~2

[ 137281-23-3 ] Synthesis Path-Downstream 1~20

Similar Product of [ 137281-23-3 ]

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Similar Product of
[ 137281-23-3 ]