756525-99-2

Basic information

• Product Name: alpha-MaleiMidopropionyl-oMega-succiniMidyl-4(ethylene glycol)
• Synonyms: alpha-MaleiMidopropionyl-oMega-succiniMidyl-4(ethylene glycol);Mal-PEG4-NHS;N-[15-[(2,5-Dioxo-1-pyrrolidinyl)oxy]-15-oxo-3,6,9,12-tetraoxapentadec-1-yl]-2,5-dihydro-2,5-dioxo-1H-pyrrole-1-propanamide;O-[N-(3-MaleiMidopropionyl)aMinoethyl]-O′-[3-(N-succiniMidyloxy)-3-oxopropyl]triethylene glycol;O-[N-(3-Maleimidopropionyl)aminoethyl]-O'-[3-(N-succinimidyloxy)-3-oxopropyl]triethylene glycol >=90% (NMR);Mal-amido-PEG4-NHS;Maleimide-NH-PEG4-CH2CH2COONHS Ester;Maleimide-PEG4-NHS Ester
• CAS NO: 756525-99-2
• Molecular Formula: C₂₂H₃₁N₃O₁₁
• Molecular Weight: 513.49504
• EINECS: 201-258-5
• Mol File: 756525-99-2.mol
• Article Data: 4

Chemical Properties

• Appearance: /
• Density: 1.36±0.1 g/cm3(Predicted)
• Storage Temp.: ?20°C
• PKA: 15.01±0.46(Predicted)
• CAS DataBase Reference: alpha-MaleiMidopropionyl-oMega-succiniMidyl-4(ethylene glycol)(CAS DataBase Reference)
• NIST Chemistry Reference: alpha-MaleiMidopropionyl-oMega-succiniMidyl-4(ethylene glycol)(756525-99-2)
• EPA Substance Registry System: alpha-MaleiMidopropionyl-oMega-succiniMidyl-4(ethylene glycol)(756525-99-2)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 756525-99-2(Hazardous Substances Data)

Usage

Description

Mal-amido-PEG4-NHS is a PEG linker containing a maleimide group and an NHS ester. The hydrophilic PEG spacer increases solubility in aqueous media. The NHS ester can be used to label the primary amines (-NH2) of proteins, amine-modified oligonucleotides, and other amine-containing molecules. The maleimide group will react with a thiol group to form a covalent bond, enabling the connection of biomolecule with a thiol.

Uses

Maleimide-PEG4-NHS (CAS# 756525-99-2) is a cross-linking compound used in the lysosomal acid-triggered release of anticancer drugs.

Synthetic route

3-[2-[2-[2-[2-(tert-butoxycarbonylamino)ethoxy]ethoxy]ethoxy]ethoxy]propanoic acid (756525-91-4) → 3-[2-[2-[2-[[3-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-propionylamino]ethoxy]ethoxy]ethoxy]ethoxy]propionic acid-2,5-dioxo-pyrrolidin-1-yl ester (756525-99-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: dichloromethane / 20 °C 2: N-ethyl-N,N-diisopropylamine / dichloromethane / 20 °C 3: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride View Scheme
Multi-step reaction with 3 steps 1: dichloromethane / 20 °C 2: N-ethyl-N,N-diisopropylamine / dichloromethane / 20 °C 3: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride View Scheme

3-maleimidopropionic acid N-hydroxysuccinimide ester (55750-62-4) + 14-carboxy-3,6,9,12-tetraoxatetradecan-1-ammonium 2,2,2-trifluoroacetate (1615234-93-9) → 3-[2-[2-[2-[[3-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-propionylamino]ethoxy]ethoxy]ethoxy]ethoxy]propionic acid-2,5-dioxo-pyrrolidin-1-yl ester (756525-99-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine / dichloromethane / 20 °C 2: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride View Scheme
Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine / dichloromethane / 20 °C 2: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride View Scheme

1-hydroxy-pyrrolidine-2,5-dione (6066-82-6) + 1-[3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)propanamido]-3,6,9,12-tetraoxapentadecan-15-oic acid (1263045-16-4) → 3-[2-[2-[2-[[3-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-propionylamino]ethoxy]ethoxy]ethoxy]ethoxy]propionic acid-2,5-dioxo-pyrrolidin-1-yl ester (756525-99-2)

Conditions	Yield
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride	0.109 g
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride	0.109 g
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride	0.109g
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 2h;	330 mg

3-maleimidepropionic acid (7423-55-4) → 3-[2-[2-[2-[[3-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-propionylamino]ethoxy]ethoxy]ethoxy]ethoxy]propionic acid-2,5-dioxo-pyrrolidin-1-yl ester (756525-99-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: dicyclohexyl-carbodiimide 2: N-ethyl-N,N-diisopropylamine / dichloromethane / 20 °C 3: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride View Scheme
Multi-step reaction with 3 steps 1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 2 h / 20 °C 2: sodium hydrogencarbonate / water; 1,2-dimethoxyethane / 2 h / 20 °C 3: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 2 h / 20 °C View Scheme

3-maleimidopropionic acid N-hydroxysuccinimide ester (55750-62-4) → 3-[2-[2-[2-[[3-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-propionylamino]ethoxy]ethoxy]ethoxy]ethoxy]propionic acid-2,5-dioxo-pyrrolidin-1-yl ester (756525-99-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydrogencarbonate / water; 1,2-dimethoxyethane / 2 h / 20 °C 2: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 2 h / 20 °C View Scheme

3-[2-[2-[2-[[3-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-propionylamino]ethoxy]ethoxy]ethoxy]ethoxy]propionic acid-2,5-dioxo-pyrrolidin-1-yl ester (756525-99-2) + N-(2-aminoethyl)-valine (243653-70-5) → C25H42N4O10 (870487-03-9)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane	97%

3-[2-[2-[2-[[3-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-propionylamino]ethoxy]ethoxy]ethoxy]ethoxy]propionic acid-2,5-dioxo-pyrrolidin-1-yl ester (756525-99-2) + C24H40N6O5 (1037794-89-0) → C42H66N8O13 (932744-54-2)

Conditions	Yield
In dichloromethane at 20℃; for 4h;	95%

3-[2-[2-[2-[[3-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-propionylamino]ethoxy]ethoxy]ethoxy]ethoxy]propionic acid-2,5-dioxo-pyrrolidin-1-yl ester (756525-99-2) + 2-(5-methoxyindol-3-yl)ethylamine (608-07-1) → 1-(3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)propanamido)-N-(2-(5-methoxy-1H-indol-3-yl)ethyl)-3,6,9,12-tetraoxapentadecan-15-amide

Conditions	Yield
In N,N-dimethyl-formamide at 20℃; for 0.5h;	92%

3-[2-[2-[2-[[3-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-propionylamino]ethoxy]ethoxy]ethoxy]ethoxy]propionic acid-2,5-dioxo-pyrrolidin-1-yl ester (756525-99-2) + tert-butyl 1-((4-(4-(3-azidopropoxy)benzoyl)phenyl)amino)-3,6,9,12-tetraoxapentadecan-15-oate → tert-butyl 1-((4-(4-((1-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-3,19-dioxo-7,10,13,16-tetraoxa-4,20-diazatricosan-23-yl)oxy)benzoyl)phenyl)amino)-3,6,9,12-tetraoxapentadecan-15-oate

Conditions	Yield
In dichloromethane at 20℃; for 3h;	90%

3-[2-[2-[2-[[3-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-propionylamino]ethoxy]ethoxy]ethoxy]ethoxy]propionic acid-2,5-dioxo-pyrrolidin-1-yl ester (756525-99-2) + L-valyl-N6-(tert-butoxycarbonyl)-L-lysine → N-[19-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-17-oxo-4,7,10,13-tetraoxa-16-azanonadecan-1-oyl]-L-valyl-N6-(tert-butoxycarbonyl)-L-lysine

Conditions	Yield
With 4-methyl-morpholine In N,N-dimethyl-formamide at 20℃;	82%

3-[2-[2-[2-[[3-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-propionylamino]ethoxy]ethoxy]ethoxy]ethoxy]propionic acid-2,5-dioxo-pyrrolidin-1-yl ester (756525-99-2) + L-glutamic acid di-tert-butyl ester hydrochloride (32677-01-3) → di-tert-butyl (2S)-2-[3-[2-[2-[2-[2-[3-(2,5-dioxopyrrol-1-yl)propanoylamino]ethoxy]ethoxy]ethoxy]ethoxy]propanoylamino]pentanedicarboxylate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 0 - 20℃; for 21h;	78%

3-[2-[2-[2-[[3-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-propionylamino]ethoxy]ethoxy]ethoxy]ethoxy]propionic acid-2,5-dioxo-pyrrolidin-1-yl ester (756525-99-2) + 3C2HF3O2*C50H61BrN12O8 + trifluoroacetic acid (76-05-1) → 2C2HF3O2*C68H87BrN14O16

Conditions	Yield
Stage #1: 3-[2-[2-[2-[[3-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-propionylamino]ethoxy]ethoxy]ethoxy]ethoxy]propionic acid-2,5-dioxo-pyrrolidin-1-yl ester; 3C2HF3O2*C50H61BrN12O8 In dichloromethane; N,N-dimethyl-formamide at 25℃; for 1h; Stage #2: trifluoroacetic acid In water; acetonitrile	77%

3-[2-[2-[2-[[3-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-propionylamino]ethoxy]ethoxy]ethoxy]ethoxy]propionic acid-2,5-dioxo-pyrrolidin-1-yl ester (756525-99-2) + tert-butyl (3-(2-(2-(3-((4-(4-(3-aminopropoxy)benzoyl)phenyl)amino)propoxy)ethoxy)ethoxy)propyl)carbamate → tert-butyl (3-(2-(2-(3-((4-(4-((1-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-3,19-dioxo-7,10,13,16-tetraoxa-4,20-diazatricosan-23-yl)oxy)benzoyl)phenyl)amino)propoxy)ethoxy)ethoxy)propyl)carbamate

Conditions	Yield
In dichloromethane at 20℃; for 3h;	76%

3-[2-[2-[2-[[3-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-propionylamino]ethoxy]ethoxy]ethoxy]ethoxy]propionic acid-2,5-dioxo-pyrrolidin-1-yl ester (756525-99-2) + C61H74N8O13 → C79H100N10O21

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane; N,N-dimethyl-formamide at 20℃; for 72h; Inert atmosphere;	76%

3-[2-[2-[2-[[3-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-propionylamino]ethoxy]ethoxy]ethoxy]ethoxy]propionic acid-2,5-dioxo-pyrrolidin-1-yl ester (756525-99-2) + maytansinol DM1 → C57H79ClN6O21S

Conditions	Yield
With triethylamine In tetrahydrofuran at 20℃; for 1h; Inert atmosphere;	75%

3-[2-[2-[2-[[3-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-propionylamino]ethoxy]ethoxy]ethoxy]ethoxy]propionic acid-2,5-dioxo-pyrrolidin-1-yl ester (756525-99-2) + L-lysine (56-87-1) → (2S)-2,6-bis[3-[2-[2-[2-[2-[3-(2,5-dioxopyrrol-1-yl)propanoylamino]ethoxy]ethoxy]ethoxy]ethoxy]propanoylamino]hexanoic acid

Conditions	Yield
In aq. phosphate buffer; N,N-dimethyl-formamide at 20℃; for 3h;	63%

3-[2-[2-[2-[[3-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-propionylamino]ethoxy]ethoxy]ethoxy]ethoxy]propionic acid-2,5-dioxo-pyrrolidin-1-yl ester (756525-99-2) + C49H58N6O11 (1343407-40-8) → C67H84N8O19 (1343407-44-2)

Conditions	Yield
With triethylamine In dichloromethane; N,N-dimethyl-formamide at 20℃;	50%
With triethylamine In dichloromethane; N,N-dimethyl-formamide at 20℃;	50%

3-[2-[2-[2-[[3-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-propionylamino]ethoxy]ethoxy]ethoxy]ethoxy]propionic acid-2,5-dioxo-pyrrolidin-1-yl ester (756525-99-2) + C33H45ClN2O10S → C55H76ClN5O21S

Conditions	Yield
In aq. phosphate buffer; N,N-dimethyl-formamide at 20℃; pH=6; Inert atmosphere;	50%

3-[2-[2-[2-[[3-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-propionylamino]ethoxy]ethoxy]ethoxy]ethoxy]propionic acid-2,5-dioxo-pyrrolidin-1-yl ester (756525-99-2) + C34H47ClN2O10S → C56H78ClN5O21S

Conditions	Yield
In N,N-dimethyl-formamide at 20℃; pH=6; Inert atmosphere;	49%

3-[2-[2-[2-[[3-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-propionylamino]ethoxy]ethoxy]ethoxy]ethoxy]propionic acid-2,5-dioxo-pyrrolidin-1-yl ester (756525-99-2) + C66H103N13O12S (1615234-89-3) → Tap-18H (1615234-83-7)

Conditions	Yield
With sodium hydrogencarbonate In acetonitrile at 20℃;	45%
With sodium hydrogencarbonate In acetonitrile at 20℃; for 12h;

3-[2-[2-[2-[[3-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-propionylamino]ethoxy]ethoxy]ethoxy]ethoxy]propionic acid-2,5-dioxo-pyrrolidin-1-yl ester (756525-99-2) + C66H103N13O12S → Tap-18H (1615234-83-7)

Conditions	Yield
With sodium hydrogencarbonate In acetonitrile at 20℃;	45%

3-[2-[2-[2-[[3-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-propionylamino]ethoxy]ethoxy]ethoxy]ethoxy]propionic acid-2,5-dioxo-pyrrolidin-1-yl ester (756525-99-2) + Val-Ala (1115-74-8, 6491-43-6, 19079-64-2, 63289-08-7, 83638-82-8, 150350-79-1, 27493-61-4) → N-[19-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-17-oxo-4,7,10,13-tetraoxa-16-azanonadecan-1-oyl]-L-valyl-L-alanine

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 20℃;	45%

3-[2-[2-[2-[[3-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-propionylamino]ethoxy]ethoxy]ethoxy]ethoxy]propionic acid-2,5-dioxo-pyrrolidin-1-yl ester (756525-99-2) + C35H49ClN2O11S → C57H80ClN5O22S

Conditions	Yield
In aq. phosphate buffer; N,N-dimethyl-formamide at 20℃; pH=6; Inert atmosphere;	44%

3-[2-[2-[2-[[3-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-propionylamino]ethoxy]ethoxy]ethoxy]ethoxy]propionic acid-2,5-dioxo-pyrrolidin-1-yl ester (756525-99-2) + ledoxantrone (113457-05-9) → ledoxantrone 3-[2-[2-[2-[2-[3-(2,5-dioxopyrol-1-ylo)propanoylamine]ethoxy]ethoxy]ethoxy]ethoxy]propanate

Conditions	Yield
With dmap In dichloromethane at 0 - 20℃; for 48h;	43%

3-[2-[2-[2-[[3-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-propionylamino]ethoxy]ethoxy]ethoxy]ethoxy]propionic acid-2,5-dioxo-pyrrolidin-1-yl ester (756525-99-2) + C77H84N12O11 → C72H86N12O15

Conditions	Yield
Stage #1: C77H84N12O11 With diethylamine In dichloromethane at 20℃; for 0.5h; Stage #2: 3-[2-[2-[2-[[3-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-propionylamino]ethoxy]ethoxy]ethoxy]ethoxy]propionic acid-2,5-dioxo-pyrrolidin-1-yl ester In dichloromethane at 20℃; for 1h;	36%

3-[2-[2-[2-[[3-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-propionylamino]ethoxy]ethoxy]ethoxy]ethoxy]propionic acid-2,5-dioxo-pyrrolidin-1-yl ester (756525-99-2) + R/S-(L-alpha-glutamyl-S-(11-{(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}-2,2-dimethyl-6,12-dioxo-5-oxa-7,11-diaza-2-silatridecan-13-yl))homocysteine/trifluoroacetic acid → R/S-(N-[19-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-17-oxo-4,7,10,13-tetraoxa-16-azanonadecan-1-oyl]-L-alpha-glutamyl-S-(11-{(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}-2,2-dimethyl-6,12-dioxo-5-oxa-7,11-diaza-2-silatridecan-13-yl))homocysteine

Conditions	Yield
With 4-methyl-morpholine In N,N-dimethyl-formamide at 20℃;	36%

3-[2-[2-[2-[[3-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-propionylamino]ethoxy]ethoxy]ethoxy]ethoxy]propionic acid-2,5-dioxo-pyrrolidin-1-yl ester (756525-99-2) + L-alpha-glutamyl-S-(11-{(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}-2,2-dimethyl-6,12-dioxo-5-oxa-7,11-diaza-2-silatridecan-13-yl)homocysteine trifluoroacetic acid → R/S-(N-[19-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-17-oxo-4,7,10,13-tetraoxa-16-azanonadecan-1-oyl]-L-alpha-glutamyl-S-(11-{(1R)-1-[1-benzyl-4-(2,5-difluorophenyl)-1H-pyrrol-2-yl]-2,2-dimethylpropyl}-2,2-dimethyl-6,12-dioxo-5-oxa-7,11-diaza-2-silatridecan-13-yl))homocysteine

Conditions	Yield
With 4-methyl-morpholine In N,N-dimethyl-formamide at 20℃;	36%

3-[2-[2-[2-[[3-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-propionylamino]ethoxy]ethoxy]ethoxy]ethoxy]propionic acid-2,5-dioxo-pyrrolidin-1-yl ester (756525-99-2) + C52H88N10O12 → C70H114N12O20

Conditions	Yield
With triethylamine at 20℃;	28%

3-[2-[2-[2-[[3-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-propionylamino]ethoxy]ethoxy]ethoxy]ethoxy]propionic acid-2,5-dioxo-pyrrolidin-1-yl ester (756525-99-2) + (S)-2-[[1-(2-amino-ethyl)-cyclopentanecarbonyl]-amino]-3-[4-(2,6-dichloro-benzoylamino)-phenyl]-propionic acid (220878-78-4) → (S)-3-[4-(2,6-dichlorobenzoylamino)phenyl]-2-[[1-[2-[3-[2-[2-[2-[2-[3-(2,5-dioxo-2,5-dihydropyrrol-1-yl)propionylamino]ethoxy]ethoxy]ethoxy]ethoxy]propionylaminol]ethyl]cyclopentanecarbonyl]amino]propionic acid

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide at 20℃; for 1h; Inert atmosphere;	26%

3-[2-[2-[2-[[3-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-propionylamino]ethoxy]ethoxy]ethoxy]ethoxy]propionic acid-2,5-dioxo-pyrrolidin-1-yl ester (756525-99-2) + bis(4-((S)-2-((S)-2-amino-3-methylbutanamido)propanamido)benzyl) 8,8'-(pentane-1,5-diyibis(oxy))(11S,11aS,11'S,11a'S)-bis(11-hydroxy-7-methoxy-2-methyl-5-oxo-11,11a-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-10(5H)-carboxylate) → bis(4-((2S,5S)-2S-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-5-isopropyl-2-methyl-4,7,23-trioxo-10,13,16,19-tetraoxa-3,6,22-triazapentacosanamido)benzyl) 8,8'-(pentane-1,5-5-diylbis(oxy))(11S,11aS,11'S,11a'S)-bis(11-hydroxy-7-methoxy-2-methyl-5-oxo-11,11adihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-10(5H)-carboxylate)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In chloroform at 20℃; for 72h;	25%
With N-ethyl-N,N-diisopropylamine In chloroform at 20℃; for 72h;	25%

3-[2-[2-[2-[[3-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-propionylamino]ethoxy]ethoxy]ethoxy]ethoxy]propionic acid-2,5-dioxo-pyrrolidin-1-yl ester (756525-99-2) + N(2')-deacetyl-N(2')-(3-mercapto-1-oxopropyl)maytansine → C57H79ClN6O21S

Conditions	Yield
In tetrahydrofuran at 20℃; for 1h; pH=6;	20.1%

3-[2-[2-[2-[[3-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-propionylamino]ethoxy]ethoxy]ethoxy]ethoxy]propionic acid-2,5-dioxo-pyrrolidin-1-yl ester (756525-99-2) + N2'-deacetyl-N2'-(3-mercapto-1-oxopropyl)maytansine → C57H79ClN6O21S

Conditions	Yield
With potassium phosphate In tetrahydrofuran; water at 20℃; for 1h; pH=6;	20%

3-[2-[2-[2-[[3-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-propionylamino]ethoxy]ethoxy]ethoxy]ethoxy]propionic acid-2,5-dioxo-pyrrolidin-1-yl ester (756525-99-2) + (S)-2-((S)-2-amino-3-methylbutanamido)-5-ureidopentanoic acid (159858-33-0) → N-[19-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-17-oxo-4,7,10,13-tetraoxa-16-azanonadecan-1-oyl]-L-valyl-N5-carbamoyl-L-ornithine

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 20℃;	14%
With triethylamine

tranexamic acid + 3-[2-[2-[2-[[3-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-propionylamino]ethoxy]ethoxy]ethoxy]ethoxy]propionic acid-2,5-dioxo-pyrrolidin-1-yl ester (756525-99-2) → 4-[(N-maleimidoethyl)carboxamidoethyl(Peg)4carboxamidomethyl]cyclohexanecarboxylic acid (951792-84-0)

Conditions	Yield
In water; N,N-dimethyl-formamide at 20℃; for 4.08333h;

3-[2-[2-[2-[[3-(2,5-dioxo-2,5-dihydro-pyrrol-1-yl)-propionylamino]ethoxy]ethoxy]ethoxy]ethoxy]propionic acid-2,5-dioxo-pyrrolidin-1-yl ester (756525-99-2) + C62H65ClN10O12 → C68H87ClN12O18

Conditions	Yield
With piperidine

Upstream product

• 55750-62-4 3-maleimidopropionic acid N-hydroxysuccinimide ester 
• 7423-55-4 3-maleimidepropionic acid 
• 6066-82-6 1-hydroxy-pyrrolidine-2,5-dione 
• 1263045-16-4 1-[3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)propanamido]-3,6,9,12-tetraoxapentadecan-15-oic acid 
• 1615234-93-9 14-carboxy-3,6,9,12-tetraoxatetradecan-1-ammonium 2,2,2-trifluoroacetate 
• 756525-91-4 3-[2-[2-[2-[2-(tert-butoxycarbonylamino)ethoxy]ethoxy]ethoxy]ethoxy]propanoic acid 

Downstream Products

• 1615234-83-7 Tap-18H 
• 932744-55-3 C₃₈H₅₈N₈O₁₃ 
• 76-05-1 trifluoroacetic acid 
• 1343407-88-4 (11S,11aS)-4-((2S,5S)-25-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-5-isopropyl-2-methyl-4,7,23-trioxo-10,13,16,19-tetraoxa-3,6,22-triazapentacosanamido)benzyl 11-hydroxy-7-methoxy-8-(3-(((S)-7-methoxy-5-oxo-2-((E)-prop-1-en-1-yl)-5,11a-dihydro-pyrrolo[2,1-c][1,4]benzodiazepin-8-yl)oxy)propoxy)-5-oxo-2-((E)-prop-1-en-1-yl)-11,11a-dihydro-pyrrolo[2,1-c][1,4]benzodiazepine-10(5H)-carboxylate 
• 1343407-44-2 C₆₇H₈₄N₈O₁₉ 
• 1037794-59-4 C₇₀H₉₁ClN₁₂O₁₈ 
• 951792-84-0 4-[(N-maleimidoethyl)carboxamidoethyl(Peg)4carboxamidomethyl]cyclohexanecarboxylic acid 

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