[ CAS No. 25021-08-3 ] {[proInfo.proName]}

Name: 25021-08-3|2-(2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetic acid|97%
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Quality Control of [ 25021-08-3 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 25021-08-3 ]

CAS No. :	25021-08-3	MDL No. :	MFCD00457254
Formula :	C₆H₅NO₄	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	GBKPNGVKZQBPCZ-UHFFFAOYSA-N
M.W :	155.11	Pubchem ID :	319935
Synonyms :		Chemical Name :	2-(2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetic acid

Calculated chemistry of [ 25021-08-3 ]

Physicochemical Properties

Num. heavy atoms :	11
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.17
Num. rotatable bonds :	2
Num. H-bond acceptors :	4.0
Num. H-bond donors :	1.0
Molar Refractivity :	37.35
TPSA :	74.68 Å²

Pharmacokinetics

GI absorption :	High
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) :	-7.35 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.53
Log Po/w (XLOGP3) :	-0.14
Log Po/w (WLOGP) :	-1.38
Log Po/w (MLOGP) :	-1.16
Log Po/w (SILICOS-IT) :	-0.65
Consensus Log Po/w :	-0.56

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.56

Water Solubility

Log S (ESOL) :	-0.58
Solubility :	40.7 mg/ml ; 0.262 mol/l
Class :	Very soluble
Log S (Ali) :	-0.97
Solubility :	16.5 mg/ml ; 0.106 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	0.6
Solubility :	619.0 mg/ml ; 3.99 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.14

Safety of [ 25021-08-3 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302+H312+H332-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 25021-08-3 ]

* 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 [ 25021-08-3 ]
Downstream synthetic route of [ 25021-08-3 ]

[ 25021-08-3 ] Synthesis Path-Upstream 1~5

1
[ 6066-82-6 ]
[ 25021-08-3 ]
[ 55750-61-3 ]

Reference： [1] Bioconjugate Chemistry, 2012, vol. 23, # 12, p. 2417 - 2433
[2] Journal of Medicinal Chemistry, 1984, vol. 27, # 10, p. 1325 - 1335

2
[ 25021-08-3 ]
[ 55750-61-3 ]

Reference： [1] Patent: CN105037237, 2017, B,

3
[ 329709-87-7 ]
[ 25021-08-3 ]

Yield	Reaction Conditions	Operation in experiment
64.5%	With triethylamine; 1-nitro-4-trifluoroacetoxy-benzene In dichloromethane at -5 - -2℃; for 3 h;	In a 1000 ml three-necked flask,The compound of formula (II) (162 g, 0.94 mol, X = 1)And 400 ml of dichloromethane,Triethylamine (284.8 g, 2.82 mol) was then added,Ice salt was cooled to -2 ° C with stirring,Phenyl 4-nitro trifluoroacetate (353.4 g, 1.5 mol) was added dropwiseIn 300 ml of dichloromethane,Controlling the temperature below -5-10 ,Dripping finished insulation stirring 3h.The reaction solution was concentrated to dryness, 400 ml of water was added, and the pH was adjusted to 3-4 with concentrated hydrochloric acid while stirring. The 4-nitrophenol was removed by filtration and the filtrate was extracted three times with dichloromethane. The combined organic phases were washed with water and dried over anhydrous magnesium sulfate Concentrated to dryness to give a pale yellow solid 129g,Ethyl acetate, petroleum ether, mixed solvent was recrystallized to give a white solid 107g, weighed after drying 94g,HPLC purity 98.2percent, yield 64.5percent.

Reference： [1] Patent: CN105037237, 2017, B, . Location in patent: Paragraph 0059-0062
[2] Chemistry - A European Journal, 2011, vol. 17, # 2, p. 468 - 480
[3] Organic and Biomolecular Chemistry, 2009, vol. 7, # 17, p. 3400 - 3406

4
[ 54930-24-4 ]
[ 25021-08-3 ]

Reference： [1] Bioconjugate Chemistry, 2010, vol. 21, # 1, p. 74 - 83
[2] RSC Advances, 2017, vol. 7, # 26, p. 16181 - 16188
[3] Organic and Biomolecular Chemistry, 2004, vol. 2, # 23, p. 3434 - 3441
[4] Angewandte Chemie - International Edition, 2005, vol. 44, # 41, p. 6750 - 6755
[5] Bioorganic Chemistry, 2006, vol. 34, # 6, p. 424 - 444
[6] Chemistry - A European Journal, 2006, vol. 12, # 34, p. 8798 - 8812
[7] Patent: US2006/128943, 2006, A1, . Location in patent: Page/Page column 6

5
[ 108-31-6 ]
[ 56-40-6 ]
[ 25021-08-3 ]

Reference： [1] Journal of Chemical Research - Part S, 1998, # 5, p. 272 - 273
[2] European Journal of Medicinal Chemistry, 2009, vol. 44, # 12, p. 5094 - 5098
[3] Organic and Biomolecular Chemistry, 2009, vol. 7, # 16, p. 3308 - 3318
[4] Organic Letters, 2010, vol. 12, # 9, p. 1920 - 1923
[5] Bioconjugate Chemistry, 2012, vol. 23, # 12, p. 2417 - 2433
[6] Patent: EP1188746, 2002, A1, . Location in patent: Page 8
[7] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 3, p. 1124 - 1127
[8] ACS Medicinal Chemistry Letters, 2015, vol. 6, # 2, p. 162 - 167
[9] Oriental Journal of Chemistry, 2018, vol. 34, # 1, p. 286 - 294
[10] Journal of Peptide Science, 2018, vol. 24, # 4-5,

[ 25021-08-3 ] Synthesis Path-Downstream 1~88

1
[ 6066-82-6 ]
[ 25021-08-3 ]
[ 55750-61-3 ]

Reference： [1]Bioconjugate Chemistry,2012,vol. 23,p. 2417 - 2433
[2]Journal of Medicinal Chemistry,1984,vol. 27,p. 1325 - 1335

2
[ 25021-08-3 ]
(5S,11S,13aR)-11-Aminomethyl-5-benzyl-decahydro-3a,6,9,12-tetraaza-cyclopentacyclododecene-4,7,10,13-tetraone; hydrochloride [ No CAS ]
[ 77087-68-4 ]

Reference： [1]Journal of Medicinal Chemistry,1981,vol. 24,p. 567 - 572

3
[ 25021-08-3 ]
[ 95-95-4 ]
[ 83100-48-5 ]

Reference： [1]Zeitschrift fur Chemie,1982,vol. 22,p. 179 - 179

4
[ 25021-08-3 ]
(5-Carboxymethyl-1,3,4,6-tetraoxo-octahydro-cyclobuta[1,2-c;3,4-c']dipyrrol-2-yl)-acetic acid [ No CAS ]

Reference： [1]Journal of Organic Chemistry,1995,vol. 60,p. 2353 - 2360

5
[ 25021-08-3 ]
[ 107-13-1 ]
(6-Cyano-2,4-dioxo-3-aza-bicyclo[3.2.0]hept-3-yl)-acetic acid [ No CAS ]

Reference： [1]Journal of Organic Chemistry,1995,vol. 60,p. 2353 - 2360

6
[ 25021-08-3 ]
[ 17686-36-1 ]

Yield	Reaction Conditions	Operation in experiment
	In thionyl chloride;	A suspension of <strong>[25021-08-3]2,5-dihydro-2,5-dioxopyrrol-1-ylacetic acid</strong> (821 mg) in thionyl chloride (15.9 ml) was heated under reflux for 0.5 hours and the excess thionyl chloride was removed under vacuum. The residue was evaporated twice with dry toluene to afford 2,5-dihydro-2,5-dioxopyrrol-1-ylacetyl chloride [(5) where m=1] as a colourless, readily hydrolyzed liquid. (The compound has been prepared previously by a less convenient route5).
	With oxalyl dichloride; In dichloromethane; for 2h;Reflux;	To a 500 ml three-necked flask, N-maleimidyl acetic acid (94 g, 0.6 mol)And dichloromethane 300ml,Oxalyl chloride (90 g, 0.72 mol) was then added,The reaction was warmed to reflux, a large amount of gas was released.After 2h the reaction became clear,Concentrate to remove methylene chloride and excess oxalyl chloride,Addition of 200 ml of methylene chloride to remove the residual acid in one pass afforded crude N-maleimidoacetyl chloride.The crude product was dissolved in 200 ml of dichloromethane,Was added dropwise to N-hydroxysuccinimide (69 g, 0.6 mol)Triethylamine (80.8 g, 0.8 mol)Dissolved in 300 ml of dichloromethane,Ice water cooling control temperature does not exceed 20 , drip finished room temperature 2h.The reaction solution was washed with 200 ml of water to remove triethylamine hydrochloride,1N hydrochloric acid 100ml washing to remove excess triethylamine,200ml saturated salt water, washed and dried,Concentrated to dry off like white solid 137g,After recrystallization from a mixed solvent of ethyl acetate and petroleum ether, 116 g of a white solid was obtained,HPLC purity 98.7%, 76.7% yield.
	With thionyl chloride; In benzene; for 7h;Reflux;	General procedure: A mixture of compound [3-7]a-i (0.01mole) and thionyl chloride (0.01mole) placed in dry benzene (10 ml.) and refluxed for 7 hours. The excess of thionyl chloride and benzene were removed under vacuum after cooling .

With thionyl chloride; for 1h;Reflux;

Compound 4 (8.53 g, 0.055 mol) was refluxed for 1 hour in thionyl chloride (40 mL).Evaporate excess thionyl chloride,The intermediate acid chloride was obtained as a dark oil.20 degrees,The oil was dissolved in dichloromethane (30 mL).And slowly added dropwise to a solution of amino compound 3 (11.66 g, 0.05 mol) and triethylamine (10.12 g, 0.1 mol) in dichloromethane (70 ml).Stirring was continued for 2 hours.The reaction solution was washed with dilute hydrochloric acid and 5% aqueous sodium hydroxide solution, respectively.The organic phase is concentrated and dried,The resulting residue was dissolved in isopropanol (60 ml) at 50 C.36% hydrochloric acid (25.35 g, 0.25 mol) was added dropwise, and stirring was continued for 2 hours.Slowly add water (100 ml),Cool to 5 degrees to precipitate a light solid.filter,The filter cake is washed with cold water.The filter cake was dried to obtain 12.57 g of product 5,The yield was 80%.

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1995,p. 1993 - 2000
[2]Patent: US5434272,1995,A
[3]European Journal of Medicinal Chemistry,2009,vol. 44,p. 5094 - 5098
[4]Journal of Organic Chemistry,2015,vol. 80,p. 9915 - 9925
[5]RSC Advances,2017,vol. 7,p. 16181 - 16188
[6]Patent: CN105037237,2017,B .Location in patent: Paragraph 0073; 0074
[7]Journal of the American Chemical Society,2017,vol. 139,p. 18522 - 18535
[8]Oriental Journal of Chemistry,2018,vol. 34,p. 286 - 294
[9]Patent: CN108892631,2018,A .Location in patent: Paragraph 0026

7
[ 827598-78-7 ]
[ 25021-08-3 ]
exo-{1-[2-(6-methyl-pyridin-2-ylcarbamoyl)-ethyl]-3,5-dioxo-10-oxa-4-aza-tricyclo[5.2.1.0^2,6]dec-8-en-4-yl}-acetic acid [ No CAS ]
endo-{1-[2-(6-methyl-pyridin-2-ylcarbamoyl)-ethyl]-3,5-dioxo-10-oxa-4-aza-tricyclo[5.2.1.0^2,6]dec-8-en-4-yl}-acetic acid [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2004,vol. 2,p. 3434 - 3441

8
((3aS,4aS,8aR,9aR)-5,6,7,8-Tetrachloro-1,3-dioxo-1,3,3a,4,4a,8a,9,9a-octahydro-benzo[f]isoindol-2-yl)-acetic acid [ No CAS ]
[ 25021-08-3 ]
C₂₀H₁₆Cl₄N₂O₈ [ No CAS ]

Reference： [1]Russian Journal of Organic Chemistry,2005,vol. 41,p. 825 - 827

9
[ 25021-08-3 ]
endo-3,4,5,6-Tetrachlorobicyclo<4.4.0>deca-2,4-diene-8,9-dicarboxylic acid N-phenylimide [ No CAS ]
C₂₄H₁₈Cl₄N₂O₆ [ No CAS ]

Reference： [1]Russian Journal of Organic Chemistry,2005,vol. 41,p. 825 - 827

10
[ 54930-24-4 ]
[ 25021-08-3 ]

Yield	Reaction Conditions	Operation in experiment
72%	With triethylamine; In toluene; at 80℃; for 2h;	The above synthesized product (500?mg, 2.89?mmol) was suspended in 75?mL of toluene. Then, after the addition of 1.4?mL of triethylamine, the suspension was left under vigorous stirring at 80?C in an oil bath until the reagent was completely dissolved (about 2?h). The resulting clear solution was separated from the brownish oil on the flask bottom by centrifugation. Toluene was removed under reduced pressure and the resulting colorless residue was dissolved in ultrapure water (about 50?mL). The pH of this solution was then adjusted to 2.0?+-?0.1 with few drops of concentrated HCl. Two extractions with ethyl acetate were carried out and the organic phase was made anhydrous with anhydrous sodium sulfate and evaporated to dryness by a rotary evaporator. The hygroscopic product was collected and dried in vacuo. Yield: 322?mg (72%). 1H NMR (DMSO-d6) delta: 4.14 (s, 2H, -OCOCH2), 7.13 (s, 1H, -NCOCH) ppm; 13C NMR (DMSO-d6) delta: 38.5 (-OCOCH2), 134.9 (-NCOCH=CH), 168.9 (-OCOCH2), 170.4 (-NCOCH=CH) ppm. ESI-MS (negative ion mode): 154?m/z [M-H]-; calcd for C6H4NO4 [M-H]- 154?m/z.
	With triethylamine; In toluene; for 1h;Heating / reflux;	A solution obtained by dissolving maleic anhydride (manufactured by Wako Pure Chemical Industries, Ltd.) of 42 parts in acetic acid of 175 parts is added to a dispersion containing glycine of 32 parts and acetic acid of 510 parts. After 3 hours reaction at room temperature, maleamic acid precipitated in the form of a white solid is separated by filtration. The solid is washed with cold water and dried to obtain a solid of 71 parts. The obtained maleamic acid of 3 parts is dispersed in triethylamine of 3.6 parts and toluene of 500 parts and dehydrated for 1 hour under refluxing condition. After spontaneous cooling, the toluene is separated by decantation and an orange-color oil phase is dried under reduced pressure. After the obtained product is dissolved in a hydrochloric acid solution and the pH of the solution is adjusted to 2 or lower, ethyl acetate extraction is carried out. The extract is dried by dehydrated magnesium sulfate and the solvent is removed by vacuum distillation to obtain carboxymethylmaleimide of 1.2 parts.

Reference： [1]Inorganica Chimica Acta,2019,vol. 488,p. 195 - 200
[2]Bioconjugate Chemistry,2010,vol. 21,p. 74 - 83
[3]RSC Advances,2017,vol. 7,p. 16181 - 16188
[4]Organic and Biomolecular Chemistry,2004,vol. 2,p. 3434 - 3441
[5]Angewandte Chemie - International Edition,2005,vol. 44,p. 6750 - 6755
[6]Bioorganic Chemistry,2006,vol. 34,p. 424 - 444
[7]Chemistry - A European Journal,2006,vol. 12,p. 8798 - 8812
[8]Patent: US2006/128943,2006,A1 .Location in patent: Page/Page column 6

11
[ 25021-08-3 ]
[ 74-88-4 ]
[ 164025-07-4 ]

Reference： [1]Organic and Biomolecular Chemistry,2004,vol. 2,p. 3434 - 3441
[2]Organic and Biomolecular Chemistry,2009,vol. 7,p. 3308 - 3318

12
{(1S,2R,6S,7R)-1-[3-(6-Methyl-pyridin-2-ylcarbamoyl)-phenyl]-3,5-dioxo-10-oxa-4-aza-tricyclo[5.2.1.0^2,6]dec-8-en-4-yl}-acetic acid [ No CAS ]
[ 247046-50-0 ]
[ 25021-08-3 ]

Reference： [1]Organic Letters,2006,vol. 8,p. 3651 - 3654

14
2-furan-3-yl-N-(6-methylpyridin-2-yl)-acetamide [ No CAS ]
[ 25021-08-3 ]
{8-[(6-methylpyridin-2-ylcarbamoyl)-methyl]-3,5-dioxo-10-oxa-4-azatricyclo[5.2.1.0^2,6]dec-8-en-4-yl}acetic acid [ No CAS ]
{8-[(6-methylpyridin-2-ylcarbamoyl)-methyl]-3,5-dioxo-10-oxa-4-azatricyclo[5.2.1.0^2,6]dec-8-en-4-yl}acetic acid [ No CAS ]

Reference： [1]Chemistry - A European Journal,2006,vol. 12,p. 6829 - 6840

15
[ 872425-85-9 ]
[ 25021-08-3 ]
{(1S,2R,6S,7R,10S)-10-[(6-Methyl-pyridin-2-ylcarbamoyl)-methyl]-3,5-dioxo-4-aza-tricyclo[5.2.2.0^2,6]undec-8-en-4-yl}-acetic acid [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2005,vol. 44,p. 6750 - 6755

17
3-furan-3-yl-N-(6-methylpyridin-2-yl)-propionamide [ No CAS ]
[ 25021-08-3 ]
exo-{8-[2-(6-methylpyridin-2-ylcarbamoyl)-ethyl]-3,5-dioxo-10-oxa-4-azatricyclo[5.2.1.0^2,6]dec-8-en-4-yl}acetic acid [ No CAS ]
endo-{8-[2-(6-methylpyridin-2-ylcarbamoyl)-ethyl]-3,5-dioxo-10-oxa-4-azatricyclo[5.2.1.0^2,6]dec-8-en-4-yl}acetic acid [ No CAS ]

Reference： [1]Chemistry - A European Journal,2006,vol. 12,p. 6829 - 6840

18
[ 247046-50-0 ]
[ 25021-08-3 ]
{(1S,2R,6S,7R)-1-[3-(6-Methyl-pyridin-2-ylcarbamoyl)-phenyl]-3,5-dioxo-10-oxa-4-aza-tricyclo[5.2.1.0^2,6]dec-8-en-4-yl}-acetic acid [ No CAS ]

Reference： [1]Organic Letters,2006,vol. 8,p. 3651 - 3654

19
[ 25021-08-3 ]
[ 104307-72-4 ]
((1S,2R,6S,7R,10S)-10-Methoxycarbonylmethyl-3,5-dioxo-4-aza-tricyclo[5.2.2.0^2,6]undec-8-en-4-yl)-acetic acid [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2005,vol. 44,p. 6750 - 6755

20
[ 25021-08-3 ]
(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-acetyl fluoride [ No CAS ]

Reference： [1]Chemistry - A European Journal,2006,vol. 12,p. 8798 - 8812

21
[ 25021-08-3 ]
[ 60-24-2 ]
C₈H₁₁NO₅S [ No CAS ]

Reference： [1]Bioorganic Chemistry,2006,vol. 34,p. 424 - 444

22
[ 25021-08-3 ]
[ 52-90-4 ]
C₉H₁₂N₂O₆S [ No CAS ]

Reference： [1]Bioorganic Chemistry,2006,vol. 34,p. 424 - 444

23
[ 25021-08-3 ]
[ 616-91-1 ]
C₁₁H₁₄N₂O₇S [ No CAS ]

Reference： [1]Bioorganic Chemistry,2006,vol. 34,p. 424 - 444

24
[ 25021-08-3 ]
[ 2485-62-3 ]
C₁₀H₁₄N₂O₆S [ No CAS ]

Reference： [1]Bioorganic Chemistry,2006,vol. 34,p. 424 - 444

25
[ 25021-08-3 ]
[ 70-18-8 ]
C₁₆H₂₂N₄O₁₀S [ No CAS ]

Reference： [1]Bioorganic Chemistry,2006,vol. 34,p. 424 - 444

26
[ 25021-08-3 ]
[ 921223-74-7 ]

Reference： [1]Chemistry - A European Journal,2006,vol. 12,p. 8798 - 8812

27
[ 25021-08-3 ]
[ 913705-69-8 ]

Reference： [1]Chemistry - A European Journal,2006,vol. 12,p. 8798 - 8812

28
[ 25021-08-3 ]
exo-{4-[(6-methylpyridin-2-ylcarbamoyl)-methyl]-3,5-dioxo-10-oxa-4-aza-tricyclo[5.2.1.0^2,6]dec-8-en-1-yl} acetic acid [ No CAS ]

Reference： [1]Chemistry - A European Journal,2006,vol. 12,p. 8798 - 8812

29
[ 25021-08-3 ]
endo-{4-[(6-methylpyridin-2-ylcarbamoyl)-methyl]-3,5-dioxo-10-oxa-4-aza-tricyclo[5.2.1.0^2,6]dec-8-en-8-yl} acetic acid [ No CAS ]

Reference： [1]Chemistry - A European Journal,2006,vol. 12,p. 8798 - 8812

30
[ 25021-08-3 ]
exo-{4-[(6-methylpyridin-2-ylcarbamoyl)-methyl]-3,5-dioxo-10-oxa-4-aza-tricyclo[5.2.1.0^2,6]dec-8-en-8-yl} acetic acid [ No CAS ]

Reference： [1]Chemistry - A European Journal,2006,vol. 12,p. 8798 - 8812

31
[ 25021-08-3 ]
{N-[2-(2,5-Dioxo-2,5-dihydro-pyrrol-1-yl)-acetyl]-N'-[1-(4-methoxy-phenyl)-meth-(E)-ylidene]-hydrazino}-acetic acid [ No CAS ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1995,p. 1993 - 2000

32
[ 25021-08-3 ]
[ 145387-28-6 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1995,p. 1993 - 2000

33
[ 25021-08-3 ]
{N-[2-(2,5-Dioxo-2,5-dihydro-pyrrol-1-yl)-acetyl]-N'-[1-(4-nitro-phenyl)-meth-(E)-ylidene]-hydrazino}-acetic acid tert-butyl ester [ No CAS ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1995,p. 1993 - 2000

34
[ 25021-08-3 ]
N-Carboxymethyl-2(2,5-dihydro-2,5-dioxopyrrol-1-yl)acetyl hydrazide hydrochloride [ No CAS ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1995,p. 1993 - 2000

35
[ 25021-08-3 ]
{N-[2-(2,5-Dioxo-2,5-dihydro-pyrrol-1-yl)-acetyl]-hydrazino}-acetic acid tert-butyl ester; hydrochloride [ No CAS ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1995,p. 1993 - 2000

36
[ 25021-08-3 ]
[ 167776-24-1 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1995,p. 1993 - 2000

37
[ 25021-08-3 ]
[ 91409-44-8 ]

Reference： [1]Journal of Medicinal Chemistry,1984,vol. 27,p. 1325 - 1335

38
[ 25021-08-3 ]
[ 83100-52-1 ]

Reference： [1]Zeitschrift fur Chemie,1982,vol. 22,p. 179 - 179

39
[ 25021-08-3 ]
[ 47225-92-3 ]
C₂₉H₂₄N₂O₁₁ [ No CAS ]

Reference： [1]Patent: EP1188746,2002,A1 .Location in patent: Page 8

40
4-(2-hydroxyethoxy)cinnamic acid-2-hydroxyethyl ester [ No CAS ]
[ 25021-08-3 ]
C₂₅H₂₂N₂O₁₁ [ No CAS ]

Reference： [1]Patent: EP1188746,2002,A1 .Location in patent: Page 9

41
[ 25021-08-3 ]
[ 818-08-6 ]
[ 666860-11-3 ]

Reference： [1]Journal of Organometallic Chemistry,2004,vol. 689,p. 238 - 245

42
[ 25021-08-3 ]
[ 818-08-6 ]
[ 666860-12-4 ]

Reference： [1]Journal of Organometallic Chemistry,2004,vol. 689,p. 238 - 245

43
polypropylene glycol [ No CAS ]
[ 25021-08-3 ]
C₁₅H₁₄N₂O₈ [ No CAS ]

Reference： [1]Patent: EP1188746,2002,A1 .Location in patent: Page 8-9

44
[ 25021-08-3 ]
N-(6-methyl-2-pyridyl)-3-methylazidobenzamide [ No CAS ]
1-([N-{6-methyl-2-pyridyl}-benzamid-3-yl]methyl-4,6-dioxo-3a,4,6a-tetrahydro-1H-pyrrolo [3,4-d][1,2,3]triazol-5-yl)-2-ethanoic acid [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2009,vol. 7,p. 3308 - 3318

45
[ 329709-87-7 ]
[ 25021-08-3 ]

Yield	Reaction Conditions	Operation in experiment
64.5%	With triethylamine; 1-nitro-4-trifluoroacetoxy-benzene; In dichloromethane; at -5 - -2℃; for 3h;	In a 1000 ml three-necked flask,The compound of formula (II) (162 g, 0.94 mol, X = 1)And 400 ml of dichloromethane,Triethylamine (284.8 g, 2.82 mol) was then added,Ice salt was cooled to -2 C with stirring,Phenyl 4-nitro trifluoroacetate (353.4 g, 1.5 mol) was added dropwiseIn 300 ml of dichloromethane,Controlling the temperature below -5-10 ,Dripping finished insulation stirring 3h.The reaction solution was concentrated to dryness, 400 ml of water was added, and the pH was adjusted to 3-4 with concentrated hydrochloric acid while stirring. The 4-nitrophenol was removed by filtration and the filtrate was extracted three times with dichloromethane. The combined organic phases were washed with water and dried over anhydrous magnesium sulfate Concentrated to dryness to give a pale yellow solid 129g,Ethyl acetate, petroleum ether, mixed solvent was recrystallized to give a white solid 107g, weighed after drying 94g,HPLC purity 98.2%, yield 64.5%.

Reference： [1]Patent: CN105037237,2017,B .Location in patent: Paragraph 0059-0062
[2]Chemistry - A European Journal,2011,vol. 17,p. 468 - 480
[3]Organic and Biomolecular Chemistry,2009,vol. 7,p. 3400 - 3406

46
[ 25021-08-3 ]
N-[3-(N'-6-methyl-2-pyridyl)-amidobenzylidine]-phenylamine N-oxide [ No CAS ]
2-((3RS,3aSR,6aRS)-3-(3-(6-methylpyridin-2-ylcarbamoyl)phenyl)-4,6-dioxo-2-phenyldihydro-2H-pyrrolo[3,4-d]isoxazol-5(3H,6H,6aH)-yl)acetic acid [ No CAS ]

Reference： [1]Organic Letters,2010,vol. 12,p. 1920 - 1923

47
[ 25021-08-3 ]
[ 1266727-26-7 ]
C₂₂H₂₁N₃O₅ [ No CAS ]
C₂₂H₂₁N₃O₅ [ No CAS ]
C₂₂H₂₁N₃O₅ [ No CAS ]

Reference： [1]Chemistry - A European Journal,2011,vol. 17,p. 468 - 480

48
[ 25021-08-3 ]
[ 960215-53-6 ]
[ 1384683-71-9 ]

Reference： [1]Chemical Communications,2012,vol. 48,p. 7134 - 7136

49
[ 25021-08-3 ]
[ 960215-53-6 ]
C₃₆H₃₃Cl⁽¹⁸⁾FN₅O₇ [ No CAS ]

Reference： [1]Chemical Communications,2012,vol. 48,p. 7134 - 7136

50
[ 25021-08-3 ]
[ 123-35-3 ]
2-[5-(4-methylpent-3-en-1-yl)-1,3-dioxo-3a,4,7,7a-tetrahydro-1H-isoindol-2(3H)-yl]acetic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	In tetrahydrofuran; at 20℃;	Imide 1 (0.20 g, 1.3 mmol) was dissolvedin 5 ml of THF. Then 0.34 ml (2.0 mmol) of myrcene was added to thissolution.The mixture was left overnight at room temperature. Thereafter,THF was removed in a vacuum and the solid residue was recrystallizedfrom n-hexane to yield 0.28 g (74%) of compound 2, mp 84-85 C. 1H NMR(CDCl3) d: 1.59 (s, 3 H, Me), 1.68 (s, 3 H, Me), 2.03 (m, 4 H, CH2), 2.26(m, 2 H, CH2), 2.56 (m, 2 H, CH2), 3.17 (ddd, 2 H, CH, 3JHH 9.2 Hz,3JHH 6.3 Hz, 3JHH 3.4 Hz), 4.25 [s, 2 H, C(O)CH2N], 5.03 (br. s, 1H, =CH),5.57 (br. s, 1H, =CH). 13C NMR (CDCl3) d: 17.7, 24.0, 25.7, 25.9, 27.5,37.2, 39.2, 39.5, 39.8, 119.8, 123.6, 131.9, 140.2, 171.5, 179.2, 179.4.IR (n/cm-1): 1748, 1676 (C=O), 2728, 2601, 2520 (COOH). MS (MALDITOF),m/z: 291.9 [M + H]+, 313.8 [M + Na]+ (calc. for [M+], m/z 291.2).Found (%): C, 65.72; H, 7.07; N, 5.10. Calc. for C16H21NO4 (%): C, 65.96;H, 7.27; N, 4.81.

Reference： [1]Mendeleev Communications,2014,vol. 24,p. 224 - 225

51
[ 25021-08-3 ]
2-(3,5-dibromo-2-hydroxyphenyl)-N-(2-nitrophenyl)acetamide [ No CAS ]
2,4-dibromo-6-(2-((2-nitrophenyl)amino)-2-oxoethyl)phenyl 2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetate [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2015,vol. 6,p. 162 - 167

52
[ 25021-08-3 ]
[ 530-62-1 ]
C₉H₇N₃O₃ [ No CAS ]

Reference： [1]RSC Advances,2015,vol. 5,p. 29653 - 29662

53
[ 25021-08-3 ]
C₁₉H₁₄O₄ [ No CAS ]
C₃₁H₂₀N₂O₁₀ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; dicyclohexyl-carbodiimide; In dichloromethane;	Then it is possible to obtain the desired compound (I-27) by an esterification reaction using a dehydrating condensing agent such as maleimide acetic acid and dicyclohexylcarbodiimide.

Reference： [1]Patent: JP5648352,2015,B2 .Location in patent: Paragraph 0046; 0047

54
[ 25021-08-3 ]
tert-butyl 3-((2-(2-((4-((tert-butyldiphenylsilyl)oxy)-2,2-dimethylbutoxy)sulfonyl)ethoxy)ethyl)amino)propanoate [ No CAS ]
tert-butyl 3-(N-(2-(2-((4-((tert-butyldiphenylsilyl)oxy)-2,2-dimethylbutoxy)sulfonyl)ethoxy)ethyl)-2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetamido)propanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 0℃; for 1h;	[0001236] To a mixture of Example 2.160.3 (557.5 mg), 2-(2,5-dioxo-2,5-dihydro- lH-pyrrol-l- yl)acetic acid (272 mg) and 0-(7-azabenzotriazol-l-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (667 mg) inN N-dimethylformamide (1.75 mL) at 0 C was added Nu,Nu- diisopropylethylamine (0.459 mL). The resulting mixture was stirred at 0 C for 1 hour. The reaction mixture was mixed with saturated aqueous NH4C1 mixture, extracted with ethyl acetate and washed with brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography, eluting with petroleum ether/ ethyl acetate (2/1), to provide the title compound. MS (LC-MS) m/e 795.3 (M+Na) +.
	With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 0℃; for 1h;	To a mixture of Example 2.160.3 (557.5 mg), 2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1- yl)acetic acid (272 mg) and O-(7-azabenzotriazol-1-yl)-N,N,N?,N?-tetramethyluronium hexafluorophosphate (667 mg) in N, N-dimethylformamide (1.75 mL) at 0 C was added N,N- diisopropylethylamine (0.459 mL). The resulting mixture was stirred at 0 C for 1 hour. The reaction mixture was mixed with saturated aqueous NH4Cl mixture, extracted with ethyl acetate and washed with brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography, eluting with petroleum ether/ ethyl acetate (2/1), to provide the title compound. MS (LC-MS) m/e 795.3 (M+Na) +.
	With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 0℃; for 1h;	To a mixture of Example 2.160.3 (557.5 mg), <strong>[25021-08-3]2-<strong>[25021-08-3](2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetic acid</strong></strong> (272 mg) and O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (667 mg) in N, N-dimethylformamide (1.75 mL) at 0 C. was added N,N-diisopropylethylamine (0.459 mL). The resulting mixture was stirred at 0 C. for 1 hour. The reaction mixture was mixed with saturated aqueous NH4Cl mixture, extracted with ethyl acetate and washed with brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography, eluting with petroleum ether/ethyl acetate (2/1), to provide the title compound. MS (LC-MS) m/e 795.3 (M+Na)+.

Reference： [1]Patent: WO2016/94509,2016,A1 .Location in patent: Paragraph 0001236
[2]Patent: WO2017/214462,2017,A2 .Location in patent: Page/Page column 670
[3]Patent: US2017/355769,2017,A1 .Location in patent: Paragraph 2215

55
[ 25021-08-3 ]
[ 123-35-3 ]
2-[5-(4-methylpent-3-en-1-yl)-1,3-dioxo-3a,4,7,7a-tetrahydro-1H-isoindol-2(3H)-yl]acetic acid [ No CAS ]

Reference： [1]Journal of Physical Organic Chemistry,2017,vol. 30

56
[ 25021-08-3 ]
[ 538-41-0 ]
C₁₈H₁₅N₅O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
51%	With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; acetonitrile; at 20℃; for 20h;	For synthesis of intermediate 1, 398 mg (1.875 mmol) of (E)-4,4?-(diazene-1,2-diyl)dianiline and 726.8 mg (4.7 mmol, 2.5 eq) of <strong>[25021-08-3]2-<strong>[25021-08-3](2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetic acid</strong></strong> were solubilized in a mixture of anhydrousDMF/acetonitrile. We then added 1.108 g (4.7 mmol, 2.5 eq) ofHATU and 0.65 mL of anhydrous triethylamine (4.7 mmol, 2.5 eq). Themixture was agitated at room temperature for 20 h. After extraction(NaHCO3, 3× ethyl acetate), the crude product was washed with acetone.The supernatant was purified by flash-column chromatography (silica)with ethyl acetate and heptane (60:40). An orange product was obtained(compound 1, 51% yield): NMR 1H (acetone-d6):delta (ppm), 9.66 (1H, s), 7.78(2H, d, J = 9.3 Hz), 7.76 (2H, d, J = 9.3 Hz), 7.71 (2H, d, J = 8.9 Hz), 7.01 (2H,s), 6.78 (2H, d, J = 8.9 Hz), and 4.41 (2H, s); NMR 13C (DMSO-d6):delta (ppm),170.64, 165.11, 152.47, 139.70, 138.55, 136.20, 134.95, 128.15, 125.90,123.50, 122.23, 118.86, 112.85, 112.52, 68.49, 55.81, 32.08, and 29.58.For synthesis of MAM-2, 200 mg (0.5725 mmol) of intermediate 1 wasmixed with 112.3 mg (1.145 mmol, 2 eq) of maleic anhydride and heatedunder microwave conditions (110 C, 90 min) in acetone. The obtainedprecipitate was filtered and resuspended in acetone and then heated 5 minat 60 C with 0.12 mL of triethylamine (0.8588 mmol, 1.5 eq). We then added0.54 mL of acetic anhydride (5.725 mmol, 10 eq) with a catalytic amount ofmanganese acetate (III), and the mixture was heated under microwaveconditions (90 min, 110 C). After addition of water and filtration, 46.1 mg ofMAM-2 was obtained (19% yield): NMR 1H (DMSO-d6):delta (ppm), 10.66 (1H, s),7.97 (2H, d, J = 8.8 Hz), 7.92 (2H, d, J = 8.8 Hz), 7.79 (2H, d, J = 8.8 Hz), 7.58(2H, d, J = 8.8 Hz), 7.23 (2H, s), 7.16 (2H, s), and 4.34 (2H, s); NMR 13C (acetone-d6):delta (ppm), 171.30, 170.38, 166.17, 152.11, 149.51, 142.76, 135.71,135.60, 135.25, 127.78, 124.83, 123.80, 120.53, and 41.46; (ESI-HMRS):(m/z,[M+H]+), 429.1073 calculated for C22H15N5O5+; found, 429.1069.

Reference： [1]Proceedings of the National Academy of Sciences of the United States of America,2017,vol. 114,p. E3786 - E3795

57
[ 25021-08-3 ]
[ 55750-61-3 ]

Reference： [1]Patent: CN105037237,2017,B

58
[ 25021-08-3 ]
C₁₉H₂₃N₅O₁₀S₂ [ No CAS ]
C₁₉H₂₃N₅O₁₀S₂ [ No CAS ]

Reference： [1]Journal of Peptide Science,2018,vol. 24

59
[ 25021-08-3 ]
C₁₉H₂₃N₅O₁₀S₂ [ No CAS ]
C₁₉H₂₃N₅O₁₀S₂ [ No CAS ]

Reference： [1]Journal of Peptide Science,2018,vol. 24

60
[ 25021-08-3 ]
C₂₀H₂₅N₅O₁₀S₂ [ No CAS ]
C₂₀H₂₅N₅O₁₀S₂ [ No CAS ]

Reference： [1]Journal of Peptide Science,2018,vol. 24

61
[ 25021-08-3 ]
C₂₃H₂₇N₅O₁₁S₂ [ No CAS ]

Reference： [1]Journal of Peptide Science,2018,vol. 24

62
[ 25021-08-3 ]
C₂₃H₂₇N₅O₁₁S₂ [ No CAS ]

Reference： [1]Journal of Peptide Science,2018,vol. 24

63
[ 25021-08-3 ]
C₂₄H₂₉N₅O₁₁S₂ [ No CAS ]

Reference： [1]Journal of Peptide Science,2018,vol. 24

64
[ 110-00-9 ]
[ 25021-08-3 ]
C₁₀H₉NO₅ [ No CAS ]

Reference： [1]Journal of Peptide Science,2018,vol. 24

65
[ 25021-08-3 ]
[ 2485-62-3 ]
C₁₀H₁₄N₂O₆S [ No CAS ]
C₁₀H₁₄N₂O₆S [ No CAS ]

Reference： [1]Journal of Peptide Science,2018,vol. 24

66
[ 25021-08-3 ]
tert-butyl 3-aminopropanoate hydrochloride [ No CAS ]
N-[(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetyl]-beta-alanine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine;	N-[(2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetyl]-beta-alanine The title compound was prepared from commercially available <strong>[25021-08-3](2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetic acid</strong> by coupling with tert-butyl beta-alaninate hydrochloride (1:1) in the presence of EDCI/HOBt and N,N-diisopropylethylamine and subsequent deprotection with trifluoroacetic acid. LC-MS (Method 1): Rt=0.32 min; MS (ESIpos): m/z=227 (M+H)+.
		N-[(2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetyl]-beta-alanine The title compound was prepared from commercially available <strong>[25021-08-3](2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetic acid</strong> by coupling to tert-butyl beta-alaninate hydrochloride (1:1) in the presence of EDCI/HOBt and N,N-diisopropylethylamine and subsequent deprotection with trifluoroacetic acid. LC-MS (Method 1): Rt=0.32 min; MS (ESIpos): m/z=227 (M+H)+.
	With benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine;	N-[(2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetyl]-beta-alanine The title compound was prepared from commercially available <strong>[25021-08-3](2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetic acid</strong> by coupling with tert-Butyl beta-alaninate hydrochloride (1:1) in the presence of EDCI/HOBt and N,N-diisopropylethylamine and subsequent deprotection with trifluoroacetic acid. LC-MS (Method 1): Rt=0.32 min; MS (ESIpos): m/z=227 (M+H)+.

Reference： [1]Patent: US2018/169256,2018,A1
[2]Patent: US2019/77752,2019,A1 .Location in patent: Paragraph 2115-2117
[3]Patent: US2020/138970,2020,A1

67
[ 25021-08-3 ]
[ 153086-78-3 ]
tert-butyl {2-[2-(2-[(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetyl]amino}ethoxy)ethoxy]ethyl}carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20℃; for 0.5h;	Trifluoroacetic acid/N-{2-[2-(2-aminoethoxy)ethoxy]ethyl}-2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetamide (1:1) 200 mg (0.805 mmol) of tert-butyl {2-[2-(2-aminoethoxy)ethoxy]ethyl}carbamate, 150 mg (0.966 mmol) of <strong>[25021-08-3](2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetic acid</strong> and 560 mul (3.2 mmol) of N,N-diisopropylethylamine were dissolved in 10 ml of dimethylformamide, and 459 mg (1.21 mmol) of HATU were added. The reaction mixture was stirred at RT for 30 minutes. The solvents were evaporated under reduced pressure and the residue was dissolved in dichloromethane. The organic phase was washed twice with 5% citric acid solution and dried over magnesium sulphate, and the solvent was evaporated under reduced pressure. The residue was purified using Biotage Isolera (silica gel, column 25 g SNAP, dichloromethane:methanol 98:2). This gave 276 mg (89% of theory) of tert-butyl {2-[2-(2-[(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetyl]amino}ethoxy)ethoxy]ethyl}carbamate. LC-MS (Method 1): Rt=0.67 min; MS (ESIpos): m/z=386 (M+H)+.
	With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate;	200 mg (0.805 mmol) of tert-butyl {2-[2-(2-aminoethoxy)ethoxy]ethyl}carbamate, 150 mg (0.966 mmol) of <strong>[25021-08-3](2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetic acid</strong> and 560 mul (3.2 mmol) of N,N-diisopropylethylamine were dissolved in 10 ml of dimethylformamide, and 459 mg (1.21 mmol) of HATU were added. The reaction mixture was stirred at RT for 30 minutes. The solvents were evaporated under reduced pressure and the residue was dissolved in dichloromethane. The organic phase was washed twice with 5% strength citric acid solution and dried over magnesium sulphate, and the solvent was evaporated under reduced pressure. The residue was purified using Biotage Isolera (silica gel, column 25 g SNAP, dichloromethane:methanol 98:2). This gave 276 mg (89% of theory) of tert-butyl {2-[2-(2-[(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetyl]amino}ethoxy)ethoxy]ethyl}carbamate. LC-MS (Method 1): Rt=0.67 min; MS (ESIpos): m/z=386 (M+H)+.

Reference： [1]Patent: US2019/77752,2019,A1 .Location in patent: Paragraph 2135-2137
[2]Patent: US2018/169256,2018,A1

68
[ 25021-08-3 ]
[ 811442-84-9 ]
tert-butyl [17-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-16-oxo-3,6,9,12-tetraoxa-15-azaheptadec-1-yl]carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
43%	With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20℃; for 1h;	200 mg (0.594 mmol) of <strong>[811442-84-9]tert-butyl (14-amino-3,6,9,12-tetraoxatetradec-1-yl)carbamate</strong>, 111 mg (0.713 mmol) of (2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetic acid and 410 mul (2.4 mmol) of N,N-diisopropylethylamine were dissolved in 6 ml of dimethylformamide, and 339 mg (0.892 mmol) of HATU were added. The reaction mixture was stirred at RT for 1 h and purified directly by preparative RP-HPLC (column: Reprosil 250×30; 10mu, flow rate: 50 ml/min, MeCN/water, 0.1% TFA). The solvents were evaporated under reduced pressure and the residue was dried under high vacuum. This gave 130 mg (43% of theory) of tert-butyl [17-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-16-oxo-3,6,9,12-tetraoxa-15-azaheptadec-1-yl]carbamate. LC-MS (Method 1): Rt=0.71 min; MS (ESIpos): m/z=474 (M+H)+.
	With N-ethyl-N,N-diisopropylamine; trifluoroacetic acid; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate;	200 mg (0.594 mmol) of <strong>[811442-84-9]tert-butyl (14-amino-3,6,9,12-tetraoxatetradec-1-yl)carbamate</strong>, 111 mg (0.713 mmol) of (2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetic acid and 410 mul (2.4 mmol) of N,N-diisopropylethylamine were dissolved in 6 ml of dimethylformamide, and 339 mg (0.892 mmol) of HATU were added. The reaction mixture was stirred at RT for 1 h and purified directly by preparative RP-HPLC (column: Reprosil 250*30; 10mu, flow rate: 50 ml/min, MeCN/water/0.1% TFA). The solvents were evaporated under reduced pressure and the residue was dried under high vacuum. This gave 130 mg (43% of theory) of tert-butyl [17-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-16-oxo-3,6,9,12-tetraoxa-15-azaheptadec-1-yl]carbamate. LC-MS (Method 1): Rt=0.71 min; MS (ESIpos): m/z=474 (M+H)+.

Reference： [1]Patent: US2019/77752,2019,A1 .Location in patent: Paragraph 2146-2148
[2]Patent: US2018/169256,2018,A1

69
[ 25021-08-3 ]
[ 756525-95-8 ]
[ 80029-43-2 ]
tert-butyl 3-[2-(2-[(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetyl]amino}ethoxy)ethoxy]propanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; trifluoroacetic acid;	250 mg (1.07 mmol) of <strong>[756525-95-8]tert-butyl 3-[2-(2-aminoethoxy)ethoxy]propanoate</strong>, 151 mg (0.974 mmol) of 2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetic acid, 224 mg (1.46 mmol) of 1-hydroxy-1H-benzotriazole hydrate and 224 mg (1.17 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride were dissolved in 5.0 ml of dimethylformamide. The reaction mixture was stirred at RT for 1 h. Ethyl acetate was added and the mixture was extracted twice with 5% strength citric acid solution and with saturated sodium bicarbonate solution. The organic phase was washed twice with saturated sodium chloride solution and dried over magnesium sulphate, and the solvent was evaporated under reduced pressure. The residue was purified by preparative RP-HPLC (column: Reprosil 250*40; 10mu, flow rate: 50 ml/min, MeCN/water/0.1% TFA). The solvents were evaporated under reduced pressure and the residue was dried under high vacuum. This gave 267 mg (64% of theory) of tert-butyl 3-[2-(2-[(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetyl]amino}ethoxy)ethoxy]propanoate. LC-MS (Method 1): Rt=0.73 min; MS (ESIpos): m/z=371 (M+H)+.
	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; trifluoroacetic acid;	250 mg (1.07 mmol) of tert-Butyl 3-[2-(2-aminoethoxy)ethoxy]propanoate, 151 mg (0.974 mmol) of 2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetic acid, 224 mg (1.46 mmol) of 1-hydroxy-1H-benzotriazole hydrate and 224 mg (1.17 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride were dissolved in 5.0 ml of dimethylformamide. The reaction mixture was stirred at RT for 1 h. Ethyl acetate was added and the mixture was extracted twice with 5% strength citric acid solution and with saturated sodium bicarbonate solution. The organic phase was washed twice with saturated sodium chloride solution and dried over magnesium sulphate, and the solvent was evaporated under reduced pressure. The residue was purified by preparative RP-HPLC (column: Reprosil 250*40; 10mu, flow rate: 50 ml/min, MeCN/water/0.1% TFA). The solvents were evaporated under reduced pressure and the residue was dried under high vacuum. This gave 267 mg (64% of theory) of tert-Butyl 3-[2-(2-[(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetyl]amino}ethoxy)ethoxy]propanoate. LC-MS (Method 1): Rt=0.73 min; MS (ESIpos): m/z=371 (M+H)+.

Reference： [1]Patent: US2018/169256,2018,A1
[2]Patent: US2020/138970,2020,A1

70
[ 25021-08-3 ]
[ 756526-06-4 ]
[ 80029-43-2 ]
tert-butyl 1-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-2-oxo-6,9,12,15,18,21,24,27-octaoxa-3-azatriacontan-30-oate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; trifluoroacetic acid;	tert-Butyl 1-amino-3,6,9,12,15,18,21,24-octaoxaheptacosan-27-oate (100 mg, 201 mumol) was initially charged in 1.0 ml of DMF, and <strong>[25021-08-3](2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetic acid</strong> (46.8 mg, 301 mumol), 1-hydroxy-1H-benzotriazole hydrate (76.9 mg, 502 mumol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (77.0 mg, 402 mumol) were added. The reaction mixture was stirred at RT overnight, and ethyl acetate was then added. The organic phase was washed twice with 5% citric acid solution, with saturated sodium hydrogencarbonate solution and once with saturated sodium chloride solution. The organic phase was dried over magnesium sulphate. The solvents were evaporated under reduced pressure and the residue was purified by preparative RP-HPLC (column: Reprosil 125*30; 10mu, flow rate: 50 ml/min, MeCN/water/0.1% TFA). The solvents were evaporated under reduced pressure and the residue was dried under high vacuum. This gave 19.1 mg (13% of theory) of tert-butyl 1-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-2-oxo-6,9,12,15,18,21,24,27-octaoxa-3-azatriacontan-30-oate. LC-MS (Method 1): Rt=0.87 min; MS (ESIpos): m/z=635 [M+H]+

Reference： [1]Patent: US2018/169256,2018,A1

71
[ 25021-08-3 ]
(2S)-4-[{(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}(hydroxyacetyl)amino]-2-([2-(trimethylsilyl)ethoxy]carbonyl}amino)butanoic acid [ No CAS ]
[ 76-05-1 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine;	Trifluoroacetic Acid/(2S)-2-amino-4-[{(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}(glycoloyl)amino]-N-{2-[(2-[(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetyl]amino}ethyl)sulphonyl]ethyl}butanamide (1:1) The title compound was prepared from Intermediate L81 by coupling with Intermediate C58 in the presence of HATU and N,N-diisopropylethylamine. In the next step, the Z protective group was removed by hydrogenation over 10% palladium on activated carbon in DCM/methanol 1:1 at RT under hydrogen standard pressure for 30 min. The deprotected intermediate was then converted by coupling with <strong>[25021-08-3](2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetic acid</strong> in the presence of HATU and N,N-diisopropylethylamine and finally by deprotection with zinc chloride into the title compound. LC-MS (Method 1): Rt=0.83 min; MS (ESIpos): m/z=785 (M+H)+.
	With N-ethyl-N,N-diisopropylamine;	Trifluoroacetic acid/(2S)-2-amino-4-[{(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}(glycoloyl)amino]-N-{2-[(2-[(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetyl]amino}ethyl)sulphonyl]ethyl}butanamide (1:1) The title compound was prepared from Intermediate L81 by coupling with Intermediate C58 in the presence of HATU and N,N-diisopropylethylamine. In the next step, the Z protective group was removed by hydrogenation over 10% palladium on activated carbon in DCM/methanol 1:1 at RT under hydrogen standard pressure for 30 min. The deprotected intermediate was then converted by coupling with <strong>[25021-08-3](2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetic acid</strong> in the presence of HATU and N,N-diisopropylethylamine and finally by deprotection with zinc chloride into the title compound. LC-MS (Method 1): Rt=0.83 min; MS (ESIpos): m/z=785 (M+H)+.

Reference： [1]Patent: US2018/169256,2018,A1
[2]Patent: US2020/138970,2020,A1

72
[ 25021-08-3 ]
[ 57260-73-8 ]
[ 76-05-1 ]

Yield	Reaction Conditions	Operation in experiment
		Trifluoroacetic Acid/N-(2-aminoethyl)-2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetamide (1:1) The title compound was prepared by classical methods of peptide chemistry from commercially available <strong>[25021-08-3](2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetic acid</strong> and tert-butyl (2-aminoethyl)carbamate.
		Trifluoroacetic acid/N-(2-aminoethyl)-2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetamide (1:1) The title compound was prepared by classical methods of peptide chemistry from commercially available <strong>[25021-08-3](2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetic acid</strong> and tert-Butyl (2-amino-ethyl)carbamate.

Reference： [1]Patent: US2018/169256,2018,A1
[2]Patent: US2020/138970,2020,A1

73
[ 25021-08-3 ]
[ 17445-33-9 ]
N-[(2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetyl]-L-valyl-N-{3-[{(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}(glycoloyl)amino]propyl}-L-alaninamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine;	N-[(2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetyl]-L-valyl-N-{3-[{(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}(glycoloyl)amino]propyl}-L-alaninamide The title compound was prepared from Example M9 first by coupling with <strong>[17445-33-9]N-[(benzyloxy)carbonyl]-L-valyl-L-alanine</strong> in the presence of HATU and N,N-diisopropylethylamine. In the next step, the Z protective group was removed by hydrogenating for 1 hour over 10% palladium on activated carbon at RT under hydrogen standard pressure and then converting the deprotected intermediate into the title compound by coupling with (2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetic acid in the presence of HATU and N,N-diisopropylethylamine. LC-MS (Method 1): Rt=1.21 min; MS (ESIpos): m/z=777 (M+H)+.

Reference： [1]Patent: US2018/169256,2018,A1

74
[ 25021-08-3 ]
N-[6-(2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanoyl]-L-valyl-L-alanyl-N₆-{(2S)-2-amino-4-[{(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}(glycoloyl)amino]butanoyl}-L-lysine [ No CAS ]

Reference： [1]Patent: US2018/169256,2018,A1

75
[ 25021-08-3 ]
N-[6-(2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanoyl]-L-valyl-N₅-carbamoyl-L-ornithyl-N₆-{(2S)-2-amino-4-[{(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}(glycoloyl)amino]butanoyl}-L-lysine [ No CAS ]

Reference： [1]Patent: US2018/169256,2018,A1

76
[ 25021-08-3 ]
2-(trimethylsilyl)ethyl 3-amino-N-[(2S)-4-[{(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}(glycoloyl)amino]-2-([2-(trimethylsilyl)ethoxy]carbonyl}amino)butanoyl]-L-alaninate [ No CAS ]

Reference： [1]Patent: US2018/169256,2018,A1
[2]Patent: US2020/138970,2020,A1

77
[ 25021-08-3 ]
2-(trimethylsilyl)ethyl 3-amino-N-[(2S)-4-[{(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}(glycoloyl)amino]-2-([2-(trimethylsilyl)ethoxy]carbonyl}amino) butanoyl]-D-alaninate [ No CAS ]

Reference： [1]Patent: US2018/169256,2018,A1
[2]Patent: US2020/138970,2020,A1

78
[ 25021-08-3 ]
N-[(2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetyl]-beta-alanyl-S-{2-[(3-aminopropyl) {(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}amino]-2-oxoethyl}-L-cysteine [ No CAS ]

Reference： [1]Patent: US2018/169256,2018,A1
[2]Patent: US2020/138970,2020,A1

79
[ 25021-08-3 ]
(2S)-2-Amino-4-[{(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}(glycoloyl)amino]-N-(2-[(2R)-2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)propanoyl]amino}ethyl)butanamide [ No CAS ]

Reference： [1]Patent: US2018/169256,2018,A1

80
[ 25021-08-3 ]
[ 76-05-1 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine;	Trifluoroacetic Acid/1-[(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetyl]piperidin-4-yl N-{(2S)-2-amino-4-[{(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}(glycoloyl)amino]butanoyl}-beta-alanyl-L-valyl-N5-carbamoyl-L-ornithinate (1:1) The synthesis was carried out by coupling of 25 mg (0.034 mmol) of Intermediate C61 and 29 mg (0.041 mmol) of Intermediate L69 in the presence of HATU and N,N-diisopropylethylamine, followed by hydrogenation with palladium on activated carbon (10%) under standard pressure, then coupling with <strong>[25021-08-3](2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetic acid</strong> in the presence of HATU and N,N-diisopropylethylamine and finally removal of the 2-(trimethylsilyl)ethoxycarbonyl protective group with zinc chloride. HPLC purification gave 11 mg (26% of theory over 4 steps). LC-MS (Method 1): Rt=0.86 min; MS (ESIpos): m/z=1061 (M+H)+.

Reference： [1]Patent: US2018/169256,2018,A1

81
[ 25021-08-3 ]
(2S)-4-[{(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}(hydroxyacetyl)amino]-2-([2-(trimethylsilyl)ethoxy]carbonyl}amino)butanoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine;	1-[(N-({(2S)-2-Amino-4-[{(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}(glycoloyl)amino]butanoyl}-3-[(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl) acetyl]amino}-D-alanyl)amino]-3,6,9,12-tetraoxapentadecan-15-oic Acid/Trifluoroacetic Acid (1:1) First, intermediate L91 was coupled with <strong>[25021-08-3](2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetic acid</strong> in the presence of HATU and N,N-diisopropylethylamine, and the Boc protective group was then removed using 12.5% strength TFA in DCM. The resulting intermediate was coupled with intermediate C58 in the presence of HATU and N,N-diisopropylethylamine and then converted into the title compound by deprotection with zinc chloride. LC-MS (Method 1): Rt=0.84 min; MS (ESIpos): m/z=984 (M+H)+.

Reference： [1]Patent: US2018/169256,2018,A1

82
[ 25021-08-3 ]
N-[(2S)-4-[{(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}(glycoloyl)amino]-2-([2-(trimethylsilyl)ethoxy]carbonyl} amino)butanoyl]-beta alanine [ No CAS ]

Reference： [1]Patent: US2018/169256,2018,A1
[2]Patent: US2020/138970,2020,A1

83
[ 25021-08-3 ]
N-[(2S)-4-[{(1R)-1-[1-Benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}(glycoloyl)amino]-2-([2-(trimethylsilyl)ethoxy]carbonyl}amino)butanoyl]-D-alanine [ No CAS ]

Reference： [1]Patent: US2018/169256,2018,A1
[2]Patent: US2020/138970,2020,A1

84
[ 25021-08-3 ]
Trifluoroacetic Acid 2-(trimethylsilyl)ethyl 3-amino-N-[(2S)-4-[{(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}(glycoloyl)amino]-2-([2-(trimethylsilyl)ethoxy]carbonyl}amino)butanoyl]-D-alaninate [ No CAS ]

Reference： [1]Patent: US2018/169256,2018,A1
[2]Patent: US2020/138970,2020,A1

85
[ 25021-08-3 ]
2-(trimethylsilyl)ethyl {(2S)-4-[{(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}(glycoloyl)amino]-1-[(2-[(2R)-2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)propanoyl]amino}ethyl)amino]-1-oxobutan-2-yl}carbamate [ No CAS ]

Reference： [1]Patent: US2018/169256,2018,A1

86
N-(1-piperazinyl)-tert-butoxycarboxamide [ No CAS ]
[ 25021-08-3 ]
[ 76-05-1 ]

Yield	Reaction Conditions	Operation in experiment
		Trifluoroacetic Acid/1-[2-(4-aminopiperazin-1-yl)-2-oxoethyl]-1H-pyrrole-2,5-dione (1:1) The title compound was prepared analogously to Intermediate L2 over 2 steps from tert-butyl piperazin-1-ylcarbamate and <strong>[25021-08-3](2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetic acid</strong>.
		Trifluoroacetic acid/1-[2-(4-aminopiperazin-1-yl)-2-oxoethyl]-1H-pyrrole-2,5-dione (1:1) The title compound was prepared analogously to Intermediate L2 over 2 steps from tert-Butyl piperazin-1-ylcarbamate and <strong>[25021-08-3](2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetic acid</strong>.

Reference： [1]Patent: US2018/169256,2018,A1
[2]Patent: US2020/138970,2020,A1

87
[ 25021-08-3 ]
[ 17445-33-9 ]
N-(3-aminopropyl)-N-{(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}-2-hydroxyacetamide [ No CAS ]
N-[(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetyl]-L-valyl-N-{3-[{(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}(glycoloyl)amino]propyl}-L-alaninamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		N-[(2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetyl]-L-valyl-N-{3-[{(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}(glycoloyl)amino]propyl}-L-alaninamide The title compound was prepared from Example M9 first by coupling to <strong>[17445-33-9]N-[(benzyloxy)carbonyl]-L-valyl-L-alanine</strong> in the presence of HATU and N,N-diisopropylethylamine. In the next step, the Z protecting group was removed by hydrogenating over 10% palladium on activated carbon at RT under hydrogen standard pressure for 1 hour and then converting the deprotected intermediate to the title compound by coupling to (2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetic acid in the presence of HATU and N,N-diisopropylethylamine. LC-MS (Method 1): Rt=1.21 min; MS (ESIpos): m/z=777 (M+H)+.

Reference： [1]Patent: US2019/77752,2019,A1 .Location in patent: Paragraph 2477-2479

88
[ 25021-08-3 ]
[ 756525-95-8 ]
tert-butyl 3-[2-(2-[(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetyl]amino}ethoxy)ethoxy]propanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃; for 1h;	250 mg (1.07 mmol) of <strong>[756525-95-8]tert-butyl 3-[2-(2-aminoethoxy)ethoxy]propanoate</strong>, 151 mg (0.974 mmol) of 2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetic acid, 224 mg (1.46 mmol) of 1-hydroxy-1H-benzotriazole hydrate and 224 mg (1.17 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride were dissolved in 5.0 ml of dimethylformamide. The reaction mixture was stirred at RT for 1 h. Ethyl acetate was added and the mixture was extracted twice with 5% citric acid solution and with saturated sodium hydrogencarbonate solution. The organic phase was washed twice with saturated sodium chloride solution and dried over magnesium sulphate, and the solvent was evaporated off under reduced pressure. The residue was purified by preparative RP-HPLC (column: Reprosil 250*40; 10mu, flow rate: 50 ml/min, MeCN/water/0.1% TFA). The solvents were evaporated under reduced pressure and the residue was dried under high vacuum. This gave 267 mg (64% of theory) of tert-butyl 3-[2-(2-[(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)acetyl]amino}ethoxy)ethoxy]propanoate. LC-MS (Method 1): Rt=0.73 min; MS (ESIpos): m/z=371 (M+H)+.

Reference： [1]Patent: US2019/77752,2019,A1 .Location in patent: Paragraph 2155-2157

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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

[ CAS No. 25021-08-3 ] {[proInfo.proName]}

Quality Control of [ 25021-08-3 ]

Related Doc. of [ 25021-08-3 ]

Product Details of [ 25021-08-3 ]

Calculated chemistry of [ 25021-08-3 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 25021-08-3 ]

Application In Synthesis of [ 25021-08-3 ]

[ 25021-08-3 ] Synthesis Path-Upstream 1~5

[ 25021-08-3 ] Synthesis Path-Downstream 1~88

Related Functional Groups of [ 25021-08-3 ]

Amides

Carboxylic Acids

Related Parent Nucleus of [ 25021-08-3 ]

Aliphatic Heterocycles

Pyrrolines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 25021-08-3 ]

Related Parent Nucleus of
[ 25021-08-3 ]