22509-74-6

Basic information

• Product Name: N-Carbethoxyphthalimide
• Synonyms: 1,3-dihydro-1,3-dioxo-2h-isoindole-2-carboxylicaciethylester;1,3-dioxo-2-isoindolinecarboxylicaciethylester;2-Isoindolinecarboxylic acid, 1,3-dioxo-, ethyl ester;Ethyl 1,3-dioxo-1,3-dihydro-2H-isoindole-2-carboxylate;Ethyl N-phthaloylcarbamate;ethyln-phthaloylcarbamate;N-Carbethoxyphtalimide;N-Karbetoksi-ftalimid
• CAS NO: 22509-74-6
• Molecular Formula: C₁₁H₉NO₄
• Molecular Weight: 219.19
• EINECS: 245-048-5
• Product Categories: Biochemistry;N-Substituted Maleimides, Succinimides & Phthalimides;N-Substituted Phthalimides;Peptide Synthesis;Protection & Derivatization Reagents (for Synthesis);Protective Reagents (Peptide Synthesis);Synthetic Organic Chemistry
• Mol File: 22509-74-6.mol
• Article Data: 20

Chemical Properties

• Melting Point: 90-92 °C(lit.)
• Boiling Point: 360°C (rough estimate)
• Flash Point: 167.815 °C
• Appearance: White/Crystalline Powder
• Density: 1.3219 (rough estimate)
• Vapor Pressure: 3.48E-05mmHg at 25°C
• Refractive Index: 1.4950 (estimate)
• Storage Temp.: 0-6°C
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: -3.02±0.20(Predicted)
• Water Solubility: insoluble
• BRN: 196340
• CAS DataBase Reference: N-Carbethoxyphthalimide(CAS DataBase Reference)
• NIST Chemistry Reference: N-Carbethoxyphthalimide(22509-74-6)
• EPA Substance Registry System: N-Carbethoxyphthalimide(22509-74-6)

Safety Data

• Hazard Codes: Xn
• Statements: 22-36/37/38-20/21/22
• Safety Statements: 22-24/25-36/37/39-26-36
• WGK Germany: 3
• RTECS: NR3459500
• F: 10
• TSCA: Yes
• HazardClass: IRRITANT
• Hazardous Substances Data: 22509-74-6(Hazardous Substances Data)

Usage

Chemical Properties

White crystalline powder

Uses

N-Carbethoxyphthalimide is used in the synthetic preparation of a novel dual binders as potent, selective, and orally bioavailable tankyrase inhibitors.

Purification Methods

Crystallise the imide from toluene/pet ether (or *benzene/pet ether). It is partly soluble in Et2O, *benzene and CHCl3. [Heller & Jacobsohn Chem Ber 54 1112 1921, Beilstein 21/10 V 428.]

InChI:InChI=1/C11H9NO4/c1-2-16-11(15)12-9(13)7-5-3-4-6-8(7)10(12)14/h3-6H,2H2,1H3

Synthetic route

chloroformic acid ethyl ester (541-41-3) + potassium phtalimide (1074-82-4) → N-ethoxycarbonylphthalimide (22509-74-6)

Conditions	Yield
With 18-crown-6 ether In toluene at 90℃; for 1h;	96%
With benzene

phthalimide (136918-14-4) + chloroformic acid ethyl ester (541-41-3) → N-ethoxycarbonylphthalimide (22509-74-6)

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide 1. 0-5 deg C, 90 min; 2. room temperature, 4 h;	95%
With dmap; triethylamine In dichloromethane at -40℃; for 0.0833333h;	94%
With triethylamine In N,N-dimethyl-formamide at 0 - 20℃; for 4h; Inert atmosphere;	94%

methanol (67-56-1) + N-ethoxycarbonylphthalimide (22509-74-6) → ethyl N-<2-(methoxycarbonyl)benzoyl>carbamate (71964-88-0)

Conditions	Yield
for 1h; Heating;	100%

L-leucine (61-90-5) + N-ethoxycarbonylphthalimide (22509-74-6) → N-phthaloyl-(S)-leucine (2419-38-7)

Conditions	Yield
With sodium carbonate In water at 20℃; for 2h;	100%
With sodium carbonate In water at 20℃; for 2h;	100%
With sodium hydrogencarbonate In water for 1h; Ambient temperature;	66%
With sodium carbonate In water	35%
With sodium carbonate In water at 20℃; for 5h;

Spermine (71-44-3) + N-ethoxycarbonylphthalimide (22509-74-6) → 1,12-diphthalimido-4,9-diazadodecane (104435-59-8)

Conditions	Yield
In chloroform at 20℃; for 1h;	100%
In dichloromethane Ambient temperature;	86%
In chloroform Ambient temperature;	70%

N-ethoxycarbonylphthalimide (22509-74-6) + 2-(cyclohexa-1,4-dien-1-yl)ethan-1-amine (21802-85-7) → 2-(2-Cyclohexa-1,4-dienyl-ethyl)-isoindole-1,3-dione (73971-98-9)

Conditions	Yield
In toluene 1) 1h ambient temperature 2) 1h reflux;	100%

serotonin creatinine sulfate monohydrate (61-47-2) + N-ethoxycarbonylphthalimide (22509-74-6) → N,N-phthalimido-2-(5-hydroxy-1H-indole-3-yl)ethylamine (53157-46-3)

Conditions	Yield
With potassium carbonate In water	100%

N-ethoxycarbonylphthalimide (22509-74-6) + 5-amino-3',5'-di-O-(tert-butyldimethylsilyl)-4,5-dihydro-2'-deoxyuridine (1204659-78-8) → 2-{1-[4-(tert-butyldimethylsiloxy)-5-(tert-butyldimethylsiloxymethyl)tetrahydrofuran-2-yl]-2,4-dioxohexahydropyrimidin-5-yl}isoindole-1,3-dione (1204659-80-2)

Conditions	Yield
In benzene for 12h; Reflux; Inert atmosphere;	100%

L-allylglycine (16338-48-0) + N-ethoxycarbonylphthalimide (22509-74-6) → (S)-2-(1,3-dioxoisoindolin-2-yl)pent-4-enoic acid (110658-33-8)

Conditions	Yield
With sodium carbonate In water at 21 - 24℃; for 3h;	99%
With triethylamine In tetrahydrofuran for 24h; Inert atmosphere; Schlenk technique; Reflux;	87%
With sodium carbonate In water for 3h;	65%

N-ethoxycarbonylphthalimide (22509-74-6) + propan-1-ol-3-amine (156-87-6) → N-(3-hydroxypropyl)phthalimide (883-44-3)

Conditions	Yield
With triethylamine In tetrahydrofuran for 6h; Ambient temperature;	99%
In chloroform for 2h; Ambient temperature; Yield given;

N-ethoxycarbonylphthalimide (22509-74-6) + (5-amino-pentyl)-(1,1-diethoxy-ethyl)-phosphinic acid ethyl ester (200402-41-1) → N-(5-((1,1-diethoxyethyl)ethoxyphosphoryl)pentyl)phthalimide (200402-42-2)

Conditions	Yield
With sodium carbonate In dichloromethane at 20℃; for 5h;	99%

ethanol (64-17-5) + N-ethoxycarbonylphthalimide (22509-74-6) → ethyl N-<2-(ethoxycarbonyl)benzoyl>carbamate (71964-89-1)

Conditions	Yield
for 36h; Heating;	98%

L-glutamic acid γ-benzyl ester (1676-73-9) + N-ethoxycarbonylphthalimide (22509-74-6) → (2S)-4-benzyloxicarbonyl-2-phthalimidobutanoic acid (88784-33-2)

Conditions	Yield
With TEA In tetrahydrofuran Heating;	98%
With sodium carbonate

N-ethoxycarbonylphthalimide (22509-74-6) + histamine dichloride (56-92-8) → 2-(2-(1H-imidazol-4-yl)ethyl)isoindoline-1,3-dione (5959-80-8)

Conditions	Yield
With sodium carbonate In water at 20℃; for 2h;	98%
With sodium carbonate In water at 20℃; for 2h;

N-ethoxycarbonylphthalimide (22509-74-6) + L-Tryptophan (73-22-3) → N-phthalimide-L-tryptophan (32675-71-1, 48208-26-0, 62361-30-2)

Conditions	Yield
Stage #1: L-Tryptophan With sodium carbonate In water Stage #2: N-ethoxycarbonylphthalimide In water at 20℃; for 2h;	98%
With sodium carbonate In water at 20℃; for 1h;	95%
With sodium carbonate In water at 20℃; for 5h;

4-aminobutyrylaldehyde diethylacetal (6346-09-4) + N-ethoxycarbonylphthalimide (22509-74-6) → 2-(4,4-diethoxybutyl)isoindoline-1,3-dione (32464-55-4)

Conditions	Yield
With sodium hydrogencarbonate for 2h; Ambient temperature;	97%
With triethylamine In tetrahydrofuran for 6h; Ambient temperature;	95%
With triethylamine In tetrahydrofuran at 20℃; for 16h; Cooling with ice;	94%

N-(3-aminopropyl)-1,4-diaminobutane (124-20-9) + N-ethoxycarbonylphthalimide (22509-74-6) → N1,N10-bisphthaloylspermidine (104435-58-7)

Conditions	Yield
In dichloromethane at 20℃; for 2.5h;	96%
In dichloromethane at 25℃; for 2h;	90%
In chloroform at 20 - 25℃; for 0.75h;	75%
at 20 - 25℃;
In chloroform Acylation;

N-ethoxycarbonylphthalimide (22509-74-6) + sodium p-aminosalicylate (133-10-8) → 2-hydroxy-4-(1,3-dioxoisoindolin-2-yl)benzoic acid (36467-52-4)

Conditions	Yield
With sodium hydrogencarbonate; triethylamine In water at 5℃; for 5h;	95.1%

11-aminoundecanoic acid (2432-99-7) + N-ethoxycarbonylphthalimide (22509-74-6) → 11-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-undecanoic acid (4403-42-3)

Conditions	Yield
With sodium carbonate In water for 6h;	95%
With sodium carbonate In water at 20℃; for 6h;	93%
With sodium carbonate In water at 25℃; for 1h;	63%
	56%

N-ethoxycarbonylphthalimide (22509-74-6) + 1-(2,5-dimethoxy-4-(6-hydroxyhexyl)phenyl)-2-aminopropane (374808-53-4) → 6-(2,5-dimethoxy-4-(2-[N,N-phthalimido]propyl)phenyl)hexanol (374808-54-5)

Conditions	Yield
With sodium hydrogencarbonate In tetrahydrofuran; water at 20℃; for 18h;	95%

tert-butyl (S)-2-amino-6-hydroxyhexanoate (873581-12-5) + N-ethoxycarbonylphthalimide (22509-74-6) → C18H23NO5 (873581-13-6)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 2h;	95%
With N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 2h;

N-ethoxycarbonylphthalimide (22509-74-6) + (2S,4S)-2-Amino-4-methyl-pentanedioic acid 1-tert-butyl ester (186828-00-2) → (2S,4S)-2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-4-methyl-pentanedioic acid 1-tert-butyl ester (186828-01-3)

Conditions	Yield
With sodium carbonate In tetrahydrofuran; water for 18h; Ambient temperature;	94%

N-ethoxycarbonylphthalimide (22509-74-6) + 3-Phenylpropan-1-amine (2038-57-5) → 2-(3-phenylpropyl)-1H-isoindole-1,3(2H)-dione (54981-86-1)

Conditions	Yield
With potassium carbonate In dichloromethane; water at 20℃;	94%

N-ethoxycarbonylphthalimide (22509-74-6) + N-(4-Amino-butyl)-2,2,2-trifluoro-acetamide → N-[4-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-butyl]-2,2,2-trifluoro-acetimidic acid (188965-96-0)

Conditions	Yield
With TEA In tetrahydrofuran Heating;	93%

N-ethoxycarbonylphthalimide (22509-74-6) + N-(4-Amino-butyl)-2,2,2-trifluoro-acetamide → N-[4-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-butyl]-2,2,2-trifluoro-acetamide (188965-96-0)

Conditions	Yield
With triethylamine In tetrahydrofuran for 12h; Heating;	93%

N-ethoxycarbonylphthalimide (22509-74-6) + (S)-methyl 2-amino-4-(methylthio)butanoate hydrochloride (2491-18-1) → methyl (S)-2-phthalimido-4-methylthiobutanoate (39739-05-4)

Conditions	Yield
With sodium carbonate In chloroform; water at 25℃; for 2h;	92%

N-ethoxycarbonylphthalimide (22509-74-6) + trans-(3R,4S)-1-(4-methoxyphenyl)-3-amino-4-<(1'S)-1',2'-O-isopropylideneethyl>-2-azetidinone (141040-22-4) → trans-(3R,4S)-1-(4-methoxyphenyl)-3-phthalimido-4-<(1'S)-1',2'-O-isopropylideneethyl>-2-azetidinone (141040-23-5)

Conditions	Yield
With sodium carbonate In tetrahydrofuran; water for 1h; Ambient temperature;	92%

N-ethoxycarbonylphthalimide (22509-74-6) + trans-3-amino-3-(4-bromophenyl)-1-cyclopropylcyclobutanol (1402603-95-5) → 2-(trans-1-(4-bromophenyl)-3-cyclopropyl-3-hydroxycyclobutyl)isoindoline-1,3-dione (1199557-06-6)

Conditions	Yield
With triethylamine In chloroform at 70℃; for 38h;	92%
With triethylamine In chloroform at 70℃; for 38h;	92%

N-ethoxycarbonylphthalimide (22509-74-6) + 2-((5,5-dimethyl-1,3,2-dioxaborinan-2-yl)methyl)-N-phenylacrylamide → ethyl 1-hydroxy-3-oxo-1-(2-(phenylcarbamoyl)allyl)isoindoline-2-carboxylate

Conditions	Yield
With potassium carbonate; zinc dibromide In chloroform at 0 - 20℃; for 12h; Inert atmosphere;	92%
With 18-crown-6 ether; potassium carbonate; zinc dibromide In chloroform

methyl 3-amino-4,6-O-benzylidene-3-deoxy-α-D-glucopyranoside (4603-89-8) + N-ethoxycarbonylphthalimide (22509-74-6) → methyl 4,6-O-benzylidene-3-deoxy-3-phthalimido-α-D-glucopyranoside (42775-84-8)

Conditions	Yield
With triethylamine In dimethyl sulfoxide at 23℃; for 16h;	91%

Upstream product

• 541-41-3 chloroformic acid ethyl ester 
• 1074-82-4 potassium phtalimide 
• 136918-14-4 phthalimide 

Downstream Products

• 49599-18-0 N-ethoxycarbonyl-phthalamic acid 
• 524-38-9 N-hydroxyphthalimide 
• 20425-27-8 (2S,5R,6R)-6-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid 
• 6707-69-3 N-(o-carboxybenzoyl)-L-leucine 
• 127-07-1 N-hydroxyurea 
• 102202-87-9 N,N-bis(phthalimidopropyl)amine 
• 64985-42-8 2-(2-(4-hydroxyphenyl)ethyl) isoindolin-1,3-dione 
• 42775-84-8 methyl 4,6-O-benzylidene-3-deoxy-3-phthalimido-α-D-glucopyranoside 
• 117679-61-5 [2-((2R,3S)-2,3-Diphenyl-aziridin-1-ylcarbamoyl)-benzoyl]-carbamic acid ethyl ester 
• 4192-28-3 Phth-L-Ala-OH 
• 2419-38-7 N-phthaloyl-(S)-leucine 
• 1221409-47-7 N-Phthaloyl-D-norleucine 
• 42406-53-1 N-phthaloyl-L-aspartic acid 
• 63273-48-3 5-phthalimido-1-pentanol 

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