6946-22-1

Basic information

• Product Name: 3-AMINOPHTHALIC ACID HYDROCHLORIDE
• Synonyms: 2-benzenedicarboxylicacid,3-amino-hydrochloride;3-AMINOPHTHALIC ACID HYDROCHLORIDE;3-AMINO-1,2-BENZENEDICARBOXYLIC ACID HYDROCHLORIDE;3-Aminophthalic acid HCL;3-AminophthalicacidHClhydrate;3-Aminophthalicacidhydrochloridelhydrate;3-AMINOPHTHALIC ACID HYDROCHLORIDE 1-HYDRATE;3-aminobenzene-1,2-dicarboxylic acid hydrochloride
• CAS NO: 6946-22-1
• Molecular Formula: C₈H₇NO₄*ClH
• Molecular Weight: 217.61
• EINECS: 230-106-4
• Product Categories: Phthalic Acids, Esters and Derivatives
• Mol File: 6946-22-1.mol
• Article Data: 5

Chemical Properties

• Melting Point: 182 °C
• Boiling Point: 436.4°C at 760 mmHg
• Flash Point: 217.7°C
• Appearance: Off-white to yellow-beige/Crystalline Powder
• Vapor Pressure: 2.17E-08mmHg at 25°C
• Storage Temp.: Inert atmosphere,Room Temperature
• Solubility: DMSO (Slightly), Methanol (Very Slightly)
• Stability: Hygroscopic
• CAS DataBase Reference: 3-AMINOPHTHALIC ACID HYDROCHLORIDE(CAS DataBase Reference)
• NIST Chemistry Reference: 3-AMINOPHTHALIC ACID HYDROCHLORIDE(6946-22-1)
• EPA Substance Registry System: 3-AMINOPHTHALIC ACID HYDROCHLORIDE(6946-22-1)

Safety Data

• Hazard Codes: Xn
• Statements: 36/37/38-22
• Safety Statements: 24/25
• TSCA: Yes
• Hazardous Substances Data: 6946-22-1(Hazardous Substances Data)

Usage

Chemical Properties

off-white to yellow-beige crystalline powder

Uses

3-Aminophthalic Acid Hydrochloride is a reactant used in the preparation of local anesthetics.

InChI:InChI=1/C8H7NO4.ClH/c9-5-3-1-2-4(7(10)11)6(5)8(12)13;/h1-3H,9H2,(H,10,11)(H,12,13);1H

Synthetic route

3-nitrophthalic acid (603-11-2) → 3-aminophthalic acid hydrochloride (6946-22-1)

Conditions	Yield
With sodium hydroxide; acetic acid; PtO2 In water; acetone	90%
With sodium hydroxide; acetic acid; PtO2 In water; acetone	90%
Stage #1: 3-nitrophthalic acid With palladium 10% on activated carbon; hydrogen In ethanol at 20 - 25℃; under 1500.15 Torr; for 3h; Autoclave; Stage #2: With hydrogenchloride In acetone at 10℃; Solvent; Pressure;	65 g
Stage #1: 3-nitrophthalic acid With palladium on activated charcoal; hydrogen at 55 - 65℃; under 5250.53 - 6750.68 Torr; for 12h; Large scale; Stage #2: With hydrogenchloride In water at -5 - 5℃; for 1h; Large scale;

3-aminophthalic acid (5434-20-8) → 3-aminophthalic acid hydrochloride (6946-22-1)

Conditions	Yield
With hydrogenchloride In water at 25℃; for 15h;	120 g

rac-α-aminoglutarimide hydrochloride (24666-56-6) + 3-aminophthalic acid hydrochloride (6946-22-1) → pomalidomide (19171-19-8)

Conditions	Yield
Stage #1: rac-α-aminoglutarimide hydrochloride; 3-aminophthalic acid hydrochloride In acetonitrile for 0.25h; Stage #2: With triethylamine In water; acetonitrile at 15 - 87℃; for 49.0833 - 50.8333h; Product distribution / selectivity;	94%
Stage #1: rac-α-aminoglutarimide hydrochloride; 3-aminophthalic acid hydrochloride In acetonitrile for 0.25h; Stage #2: With 1H-imidazole In water; acetonitrile at 15 - 87℃; for 7.08333 - 10.8333h; Product distribution / selectivity;	92%
Stage #1: rac-α-aminoglutarimide hydrochloride; 3-aminophthalic acid hydrochloride With acetic acid In acetonitrile for 0.25h; Stage #2: With 1H-imidazole In water; acetonitrile at 15 - 87℃; for 7.08333 - 10.8333h; Product distribution / selectivity;	85%
Stage #1: rac-α-aminoglutarimide hydrochloride; 3-aminophthalic acid hydrochloride With acetic acid In acetonitrile for 0.25h; Stage #2: With triethylamine In water; acetonitrile at 15 - 87℃; for 7.08333 - 10.8333h; Product distribution / selectivity;	84%
With acetic acid; triethylamine In acetone at 80 - 85℃; for 6h;	68.5%

3-aminophthalic acid hydrochloride (6946-22-1) + acryloyl chloride (814-68-6) → 3-acrylamide-1,2-benzene dicarboxylic acid

Conditions	Yield
In sodium hydroxide	92%
In sodium hydroxide	92%

4-(S)-amino-δ-valerolactam hydrochloride (672883-95-3) + 3-aminophthalic acid hydrochloride (6946-22-1) → (S)-4-amino-2-(6-oxopiperidin-3-yl)isoindoline-1,3-dione

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 80℃; for 18h; Inert atmosphere;	47%

hydrogenchloride (7647-01-0) + 3-aminophthalic acid hydrochloride (6946-22-1) → meta-aminobenzoic acid (99-05-8)

water (7732-18-5) + 3-aminophthalic acid hydrochloride (6946-22-1) → meta-aminobenzoic acid (99-05-8)

ethanol (64-17-5) + CYANAMID (420-04-2) + 3-aminophthalic acid hydrochloride (6946-22-1) → C11H11N3O3 (1413945-04-6)

Conditions	Yield
With hydrogenchloride In water for 6h; Reflux;
With hydrogenchloride In water for 6h; Reflux;

3-aminophthalic acid hydrochloride (6946-22-1) → C17H25N5O (1413944-11-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: hydrogenchloride / water / 6 h / Reflux 2.1: benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; 1,8-diazabicyclo[5.4.0]undec-7-ene / N,N-dimethyl-formamide / 1 h / 20 °C 2.2: 15 h / 20 °C View Scheme

3-aminophthalic acid hydrochloride (6946-22-1) → Apremilast (608141-41-9)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: water / 15 h / 100 °C 2.1: acetic acid / 15 h / Reflux 2.2: 3.25 h / 25 °C / Reflux View Scheme
Multi-step reaction with 2 steps 1.1: 2 h / 110 °C 2.1: acetonitrile / 80 - 85 °C 2.2: 60 - 65 °C View Scheme
Multi-step reaction with 2 steps 1: 2 h / 110 °C 2: acetonitrile / 3 h / Reflux View Scheme

acetic anhydride (108-24-7) + 3-aminophthalic acid hydrochloride (6946-22-1) → 3-acetylaminophthalic anhydride (6296-53-3)

Conditions	Yield
In water at 100℃; for 15h;	94 g
at 110℃; for 2h;	45 g
at 80 - 140℃; for 3h;

3-aminophthalic acid hydrochloride (6946-22-1) → 4-amino-2-[(1S)-1-(3-ethoxy 4-methoxyphenyl)-2-methanesulfonylethyl]-2,3-dihydro-1H-isoindole-1,3-dione (635705-72-5)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: 2 h / 110 °C 2.1: acetonitrile / 80 - 85 °C 2.2: 60 - 65 °C 3.1: hydrogenchloride / methanol View Scheme
Multi-step reaction with 3 steps 1: 2 h / 110 °C 2: acetonitrile / 3 h / Reflux 3: hydrogenchloride / methanol View Scheme

3-aminophthalic acid hydrochloride (6946-22-1) → (S)-N-(2-(1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulphonyl)ethyl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl)acetamide dimethylcarbonate

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 2 h / 110 °C 2.1: acetonitrile / 2 h / Reflux 2.2: 85 - 90 °C View Scheme

Upstream product

• 5434-20-8 3-aminophthalic acid 
• 603-11-2 3-nitrophthalic acid 

Downstream Products

• 99-05-8 meta-aminobenzoic acid 
• 608141-41-9 Apremilast 
• 6296-53-3 3-acetylaminophthalic anhydride 
• 635705-72-5 4-amino-2-[(1S)-1-(3-ethoxy 4-methoxyphenyl)-2-methanesulfonylethyl]-2,3-dihydro-1H-isoindole-1,3-dione 
• 19171-19-8 pomalidomide 

Relevant articles and documents

PROCESS FOR PREPARATION OF APREMILAST

The present invention relates to a process for preparation of apremilast. The present invention relates to p-xylene solvate of apremilast and process for its preparation.

Preparation method of Apremilast and intermediate

The invention provides a preparation method of Apremilast and its intermediate. The invention provides an Apremilast intermediate as shown in the formula III. According to the preparation method, the compound as shown in the formula III reacts with methanesulfinate to obtain a compound as shown in the formula IV; the compound as shown in the formula IV undergoes reductive amination to obtain a compound as shown in the formula V; the compound as shown in the formula V and asymmetry acid undergo salifying to obtain a compound as shown in the formula VI; and the compound as shown in the formula VI reacts with 3-acetamido-phthalic anhydride to obtain Apremilast. By the method for synthesizing Apremilast, usage of an n-butyllithium hexane solution can be avoided. Production cost is reduced, and operation process is convenient. In addition, safety in the industrial production is raised to a great extent, and the preparation method is more suitable for industrial continuous production. According to the preparation method of 3-acetamido-phthalic anhydride, yield is raised to 81%. As the yield is high, the method provided by the invention is extremely suitable for industrial production of Apremilast.

Acrylamide copolymers containing (meth)acrylamide benzene dicarboxylic units

[From equivalent EP0434145A2] New acrylamide copolymers formed by (met)acrylamide benzene dicarboxylic monomer units in accordance with the following formula: ψψ ψwherein R is H or CH3; X is H or an alcaline metal or NH4; and wherein the COOX groups may be in ortho-, meta- or para- position in relation to each other, preferably being in ortho- position to each other; and of (met)acrylamide monomer (II) units.ψ