29331-92-8

Basic information

• Product Name: 10,11-DIHYDRO-10-HYDROXYCARBAZEPINE
• Synonyms: 10,11-Dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide;10-Hydroxy-10,11-dihydrocarbamezepine;BIA 2-005;GP 47779;Licarbazepine;10,11-Dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide-d3;10,11-Dihydro-10-hydroxycarbazepine-d3;10-Hydroxy-10,11-dihydrocarbamezepine-d3
• CAS NO: 29331-92-8
• Molecular Formula: C₁₅H₁₄N₂O₂
• Molecular Weight: 254.28
• Product Categories: Intermediates & Fine Chemicals;Metabolites & Impurities;Pharmaceuticals;Isotope Labeled Compounds
• Mol File: 29331-92-8.mol
• Article Data: 20

Chemical Properties

• Melting Point: 186-189°C
• Boiling Point: 431.3°Cat760mmHg
• Flash Point: 2℃
• Appearance: /
• Density: 1.336
• Vapor Pressure: 3.33E-08mmHg at 25°C
• Refractive Index: 1.677
• Storage Temp.: Store at RT
• PKA: 13.75±0.20(Predicted)
• BRN: 1540211
• CAS DataBase Reference: 10,11-DIHYDRO-10-HYDROXYCARBAZEPINE(CAS DataBase Reference)
• NIST Chemistry Reference: 10,11-DIHYDRO-10-HYDROXYCARBAZEPINE(29331-92-8)
• EPA Substance Registry System: 10,11-DIHYDRO-10-HYDROXYCARBAZEPINE(29331-92-8)

Safety Data

• Hazard Codes: N,Xn,F
• Statements: 51/53-36-20/21/22-11
• Safety Statements: 61-36/37-26-16
• RIDADR: UN 3077 9 / PGIII
• WGK Germany: 3
• Hazardous Substances Data: 29331-92-8(Hazardous Substances Data)

Usage

Chemical Properties

White Solid

Uses

Different sources of media describe the Uses of 29331-92-8 differently. You can refer to the following data:
1. A metabolite of Oxcarbazepine
2. A labelled metabolite of Oxcarbazepine
3. 10,11-dihydro-10-hydroxy Carbamazepinee is the active metabolite of oxcarbazepine . Oxcarbazepine is rapidly and almost completely converted to 10,11-dihydro-10-hydroxycarbamazepine, which then demonstrates anticonvulsant efficacy by modulating several ion channels and receptors. ?10,11-dihydro-10-hydroxy Carbamazepine is reported to inhibit both voltage-gated Na+ and Ca2+ channels, to potentiate voltage-gated K+ channels, to antagonize adenosine A1 receptors, to increase dopaminergic transmission, and to inhibit glutamate release.

Definition

ChEBI: A dibenzoazepine that is 5H-dibenzo[b,f]azepine, reduced across the C-10,11 positions and carrying a carbamoyl substituent at the azepine nitrogen and a hydroxy function at C-10. A voltage-gated sodium channel b ocker with anticonvulsant and mood-stabilizing effects, it is related to oxcarbazepine and is an active metabolite of oxcarbazepine.

InChI:InChI=1/C15H14N2O2/c16-15(19)17-12-7-3-1-5-10(12)9-14(18)11-6-2-4-8-13(11)17/h1-8,14,18H,9H2,(H2,16,19)

Synthetic route

oxcarbazepine (28721-07-5) → 10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (29331-92-8)

Conditions	Yield
With sodium tetrahydroborate In methanol; water at 20 - 45℃; for 1.5h;	97.3%
With sodium tetrahydroborate In ethanol; water at 45 - 50℃;	94%
With sodium tetrahydroborate; water In methanol at 25 - 65℃; for 2.75h;	93.8%

carbamazepine 10,11-epoxide (36507-30-9) → 10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (29331-92-8)

Conditions	Yield
With palladium 10% on activated carbon; ammonium formate In methanol; dichloromethane; water at 20℃; for 1h; Inert atmosphere;	93%
With palladium 10% on activated carbon; ammonium formate In methanol; dichloromethane; water at 20℃; for 1h; Inert atmosphere;	93%
With hydrogen; triethylamine; palladium on activated charcoal In methanol; water at 50 - 55℃; under 7500.75 - 11251.1 Torr; for 1.66667h;	82%
With 5%-palladium/activated carbon; hydrogen; triethylamine In methanol; water under 750.075 Torr; for 2h;	63%

10-chloro-10,11-dihydro-5H-dibenz/b,f/azepine-5-carboxamide (791633-38-0) → 10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (29331-92-8)

Conditions	Yield
With water at 20℃; for 48h;	90%
With water In 1,3-dioxane; water at 50℃; for 0.666667h;	69%

5-Carbamoyl-5H-dibenz[b,f]azepinEN5-Cyano-10-hydroxy-10,11-dihydro-5H-dibenz[b,f]azepine (356760-08-2) → 10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (29331-92-8)

Conditions	Yield
With sodium perborate; ethanol; water for 0.05h; Product distribution / selectivity; Microwave irradiation;	69%
With sodium perborate; water In ethanol for 0.05h; Product distribution / selectivity; Microwave irradiation;	69%
With Oxone; sodium hydroxide; water In acetone for 2h; pH=7.5; Product distribution / selectivity; Aqueous phosphate buffer; Heating / reflux;	67%

10,11-Dihydrocarbamazepin (3564-73-6) → 10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (29331-92-8)

Conditions	Yield
Streptomyces violascens;

10,11-Dihydrocarbamazepin (3564-73-6) → oxcarbazepine (28721-07-5) + 10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (29331-92-8) + 10,11-dioxo-10,11-dihydro-dibenzo[b,f]azepine-5-carboxylic acid amide + 10-hydroperoxy-10,11-dihydro-dibenzo[b,f]azepine-5-carboxylic acid amide

Conditions	Yield
With N-hydroxyphthalimide; oxygen; benzaldehyde; nickel diacetate In acetic acid at 22℃; under 750.06 Torr; for 5h; Product distribution; Further Variations:; Catalysts; Reagents; Solvents; reaction time;	A 27 % Chromat. B 9 % Chromat. C 1 % Chromat. D 10 % Chromat.

carbamazepin (298-46-4) → 10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (29331-92-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium permanganate on alumina; sodium carbonate; peroxyacetic acid; acetic acid / dichloromethane / 1.67 h / Reflux 2: ammonium formate; palladium 10% on activated carbon / dichloromethane; methanol; water / 1 h / 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1: peracetic acid; sodium carbonate; potassium permanganate; aluminum oxide / dichloromethane / 2 h / 20 °C 2: triethylamine; 5%-palladium/activated carbon; hydrogen / water; methanol / 2 h / 750.08 Torr View Scheme
Multi-step reaction with 2 steps 1: sodium carbonate; acetic acid; perpropionic acid; / dichloromethane / 2 h / 20 °C / Reflux 2: ammonium formate; palladium 10% on activated carbon / dichloromethane; methanol; water / 1 h / 20 °C / Inert atmosphere View Scheme

10,11-dihydro-5H-dibenzo[b,f]azepin-10-one (21737-58-6) → 10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (29331-92-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: dichloromethane / 0 - 5 °C / Inert atmosphere 2: sodium tetrahydroborate / water; ethanol / 45 - 50 °C View Scheme

10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (29331-92-8) + acetic anhydride (108-24-7) → Licarbazepine acetate

Conditions	Yield
With pyridine; dmap In dichloromethane at 20℃; for 0.5h;	96%
With pyridine Reflux;	86%
With triethylamine In dichloromethane Solvent; Reagent/catalyst;	4.6 kg

10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (29331-92-8) + Methoxyacetyl chloride (38870-89-2) → licarbazepine methoxyacetate (1296102-92-5)

Conditions	Yield
With pyridine; dmap In dichloromethane at 20℃;	95%

10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (29331-92-8) + (1R,2S,5R)-menthyl chloroformate (14602-86-9) → carbonic acid 5-carbamoyl-10,11-dihydro-5H-dibenzo[b,f]azepin-10-yl ester 2-isopropyl-5-methyl-cyclohexyl ester

Conditions	Yield
With pyridine; dmap In dichloromethane for 1h; Ambient temperature;	92%

10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (29331-92-8) + (1S)-(-)-camphanic chloride (39637-74-6) → 4,7,7-trimethyl-3-oxo-2-oxa-bicyclo[2.2.1]heptane-1-carboxylic acid 5-carbamoyl-10,11-dihydro-5H-dibenzo[b,f]azepin-10-yl ester

Conditions	Yield
With pyridine; dmap In dichloromethane for 1h; Ambient temperature;	90%

10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (29331-92-8) → oxcarbazepine (28721-07-5)

Conditions	Yield
With peracetic acid; potassium dichromate; hydrogen In 1,2-dichloro-ethane at 20℃; for 1h;	90%
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dichloromethane at 25 - 30℃; for 0.25h;	65.5%
Stage #1: 10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In dichloromethane at 25 - 30℃; for 0.25h; Stage #2: With sodium hypochlorite; sodium hydrogencarbonate In dichloromethane; water at 0 - 5℃; for 1h; pH=9.7;	1.3 g

10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (29331-92-8) + (3R-trans)-dihydro-2,5-dioxofuran-3,4-diyl diacetate (6283-74-5) → C23H22N2O9 (475674-43-2)

Conditions	Yield
Stage #1: 10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide With pyridine; dmap In dichloromethane at 25 - 30℃; for 0.25h; Stage #2: (3R-trans)-dihydro-2,5-dioxofuran-3,4-diyl diacetate In dichloromethane at 25 - 30℃; for 2h; Stage #3: With water In dichloromethane at 15 - 20℃; for 4h;	88.9%

10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (29331-92-8) + (3R-trans)-dihydro-2,5-dioxofuran-3,4-diyl diacetate (6283-74-5) → (10S)-10-hydroxy-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide tartarate

Conditions	Yield
Stage #1: 10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide With pyridine; dmap In dichloromethane at 25 - 30℃; for 0.25h; Stage #2: (3R-trans)-dihydro-2,5-dioxofuran-3,4-diyl diacetate In dichloromethane at 25 - 30℃; for 2h; Reagent/catalyst;	88.9%

10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (29331-92-8) + chloroformic acid ethyl ester (541-41-3) → licarbazepine ethyl carbonate

Conditions	Yield
With pyridine; dmap In dichloromethane for 1h; Ambient temperature;	87%
With pyridine In dichloromethane at 20℃; for 1h;	72%

10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (29331-92-8) + acetyl chloride (75-36-5) → Licarbazepine acetate

Conditions	Yield
With pyridine; dmap In dichloromethane for 1h; Ambient temperature;	85%
With N-ethyl-N,N-diisopropylamine; dmap In dichloromethane at 20 - 25℃; for 1h;
With pyridine In dichloromethane at 0 - 25℃; for 5h; Large scale;	2.65 kg
With pyridine; dmap In dichloromethane at 0 - 20℃; Inert atmosphere;

10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (29331-92-8) + propionic acid anhydride (123-62-6) → (RS)-10,11-dihydro-10-propionyloxy-5H-dibenz[b,f]azepine-5-carboxamide

Conditions	Yield
With pyridine Reflux;	85%

10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (29331-92-8) + benzoyl chloride (98-88-4) → (RS)-10-benzoyloxy-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide

Conditions	Yield
With pyridine; dmap In dichloromethane for 1h; Ambient temperature;	84%

10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (29331-92-8) + butyric acid (107-92-6) → (RS)-10-butyroxy-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane Ambient temperature;	80%

nicotinic acid (59-67-6) + 10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (29331-92-8) → nicotinic acid 5-carbamoyl-10,11-dihydro-5H-dibenzo[b,f]azepin-10-yl ester

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane Ambient temperature;	76%

10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (29331-92-8) + propionic acid (802294-64-0) → (RS)-10,11-dihydro-10-propionyloxy-5H-dibenz[b,f]azepine-5-carboxamide

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane Ambient temperature;	75%

10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (29331-92-8) + L-menthoxyacetyl chloride (15356-62-4) → (2-isopropyl-5-methyl-cyclohexyloxy)-acetic acid 5-carbamoyl-10,11-dihydro-5H-dibenzo[b,f]azepin-10-yl ester

Conditions	Yield
With pyridine; dmap In dichloromethane for 1h; Ambient temperature;	71%

10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (29331-92-8) + t-Boc-L-valine (13734-41-3) → 2-tert-butoxycarbonylamino-3-methyl-butyric acid 5-carbamoyl-10,11-dihydro-5H-dibenzo[b,f]azepin-10-yl ester

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane Ambient temperature;	66%

4-Methoxyphenylacetic acid (104-01-8) + 10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (29331-92-8) → (4-methoxy-phenyl)-acetic acid 5-carbamoyl-10,11-dihydro-5H-dibenzo[b,f]azepin-10-yl ester

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane Ambient temperature;	60%

10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (29331-92-8) + valproic acid (99-66-1) → 10-[(2-propyl)pentanoyloxy]-10,11-dihydro-5H-dibenz/b,f/azepine-5-carboxamide

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane Ambient temperature;	59%

10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (29331-92-8) + O-acetylsalicyloyl chloride (5538-51-2) → 10-(2-acetoxybenzoyloxy)-10,11-dihydro-5H-dibenz/b,f/azepine-5-carboxamide

Conditions	Yield
With pyridine; dmap In dichloromethane for 1h; Ambient temperature;	56%

10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (29331-92-8) + chloroacetic acid (79-11-8) → chloro-acetic acid 5-carbamoyl-10,11-dihydro-5H-dibenzo[b,f]azepin-10-yl ester

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane Ambient temperature;	55%

10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (29331-92-8) + (R,S)-2-chloropropionic acid (598-78-7) → 2-chloro-propionic acid 5-carbamoyl-10,11-dihydro-5H-dibenzo[b,f]azepin-10-yl ester

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane Ambient temperature;	55%

10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (29331-92-8) + 4-nitrobenzeneacetic acid (104-03-0) → 10-(4-nitrophenyl)acetoxy-10,11-dihydro-5H-dibenz/b,f/azepine-5-carboxamide

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane Ambient temperature;	52%

10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (29331-92-8) + (S)-2-chloro-2-oxo-1-phenylethyl acetate (51019-44-4) → acetoxy-phenyl-acetic acid 5-carbamoyl-10,11-dihydro-5H-dibenzo[b,f]azepin-10-yl ester

Conditions	Yield
With pyridine; dmap In dichloromethane for 1h; Ambient temperature;	52%

10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (29331-92-8) + 2-ethylvaleric acid (20225-24-5) → 2-ethyl-pentanoic acid 5-carbamoyl-10,11-dihydro-5H-dibenzo[b,f]azepin-10-yl ester

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane Ambient temperature;	50%

10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (29331-92-8) + pivaloyl chloride (3282-30-2) → 2,2-dimethyl-propionic acid 5-carbamoyl-10,11-dihydro-5H-dibenzo[b,f]azepin-10-yl ester

Conditions	Yield
With pyridine; dmap In dichloromethane for 1h; Ambient temperature;	50%

10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (29331-92-8) + benzoic acid anhydride (93-97-0) → (RS)-10-benzoyloxy-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide

Conditions	Yield
With pyridine Reflux;	50%

Upstream product

• 21737-58-6 10,11-dihydro-5H-dibenzo[b,f]azepin-10-one 
• 298-46-4 carbamazepin 
• 356760-08-2 5-Carbamoyl-5H-dibenz[b,f]azepinEN₅-Cyano-10-hydroxy-10,11-dihydro-5H-dibenz[b,f]azepine 
• 36507-30-9 carbamazepine 10,11-epoxide 
• 791633-38-0 10-chloro-10,11-dihydro-5H-dibenz/b,f/azepine-5-carboxamide 
• 3564-73-6 10,11-Dihydrocarbamazepin 
• 28721-07-5 oxcarbazepine 

Downstream Products

• 186694-45-1 Licarbazepine acetate 
• 104746-03-4 R-licarbazepine 
• 186694-45-1 eslicarbazepine acetate 
• 104746-04-5 S-licarbazepine 
• 186694-45-1 (+)-Licarbazepine acetate 
• 28721-07-5 oxcarbazepine 
• 1399078-91-1 C₂₉H₃₁N₃O₅ 
• 1399078-93-3 C₂₉H₃₁N₃O₅ 
• 1346462-64-3 (S)-((S)-5-carbamoyl-10,11-dihydro-5H-dibenzo[b,f]azepin-10-yl) 1-benzylpyrrolidine-2-carboxylate 
• 1346462-62-1 (R)-((S)-5-carbamoyl-10,11-dihydro-5H-dibenzo[b,f]azepin-10-yl) 1-benzylpyrrolidine-2-carboxylate 
• 1346462-63-2 (S)-((S)-5-carbamoyl-10,11-dihydro-5H-dibenzo[b,f]azepin-10-yl) 2-amino-2-phenylacetate 
• 1335227-37-6 (10S)-10-[(2R)-(acetyloxy)(phenyl)ethanoate]-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide 

Relevant articles and documents

Brain-targeting eslicarbazepine ester prodrug and application thereof

The invention relates to an eslicarbazepine ester prodrug and an application thereof, wherein the prodrug is a compound represented by the formula (I) or optical isomers or physiologically acceptable salts of the compound represented by the formula (I), wherein R represents a lipophilic substituent. The compound represented by the formula (I) is the eslicarbazepine ester prodrug containing the lipophilic substituent, is converted into eslicarbazepine through metabolism in vivo to play pharmacological effects, and can be applied in preparation of drugs for treatment, prevention or adjuvant treatment of central nervous system diseases, such as epilepsy and the like.

COMPOSITIONS AND METHODS FOR THE TREATMENT OF NEUROLOGICAL DISORDERS

The invention relates to the compounds of formula I and formula IA or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I and formula IA; and methods for treating or preventing neurological diseases may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of epilepsy, bipolar disorder, trigeminal neuralgia, attention-deficit hyperactivity disorder (ADHD), schizophrenia, neuropathic pain, seizures, bipolar disorder, mania, phantom limb syndrome, complex regional pain syndrome, paroxysmal extreme pain disorder, neuromyotonia, intermittent explosive disorder, borderline personality disorder, Myotonia congenita and post-traumatic stress disorder.