[ CAS No. 29331-92-8 ] {[proInfo.proName]}

Name: 29331-92-8|10-Hydroxy-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide|97%
Brand: Ambeed
SKU: A334944
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Quality Control of [ 29331-92-8 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 29331-92-8 ]

SDS Specification

Alternatived Products of [ 29331-92-8 ]

Product Details of [ 29331-92-8 ]

CAS No. :	29331-92-8	MDL No. :
Formula :	C₁₅H₁₄N₂O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	BMPDWHIDQYTSHX-UHFFFAOYSA-N
M.W :	254.28	Pubchem ID :	114709
Synonyms :	BIA 2-005;GP 47779;TRI-477;LIC-477D;LIC-477;10,11-hydroxy-10,11 Dihydrocarbamezer;10,11-dihydro-10-hydroxy CBZ;10,11-dihydro-10-hydroxy Carbamazepine

Calculated chemistry of [ 29331-92-8 ]

Physicochemical Properties

Num. heavy atoms :	19
Num. arom. heavy atoms :	12
Fraction Csp3 :	0.13
Num. rotatable bonds :	1
Num. H-bond acceptors :	2.0
Num. H-bond donors :	2.0
Molar Refractivity :	76.1
TPSA :	66.56 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	Yes
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.82 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.98
Log Po/w (XLOGP3) :	1.45
Log Po/w (WLOGP) :	1.79
Log Po/w (MLOGP) :	2.22
Log Po/w (SILICOS-IT) :	1.14
Consensus Log Po/w :	1.72

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	0.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-2.73
Solubility :	0.472 mg/ml ; 0.00186 mol/l
Class :	Soluble
Log S (Ali) :	-2.45
Solubility :	0.895 mg/ml ; 0.00352 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.59
Solubility :	0.0654 mg/ml ; 0.000257 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	0.0
Synthetic accessibility :	3.08

Safety of [ 29331-92-8 ]

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

Application In Synthesis of [ 29331-92-8 ]

* 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 [ 29331-92-8 ]
Downstream synthetic route of [ 29331-92-8 ]

[ 29331-92-8 ] Synthesis Path-Upstream 1~8

1
[ 36507-30-9 ]
[ 29331-92-8 ]

Yield	Reaction Conditions	Operation in experiment
93%	With palladium 10% on activated carbon; ammonium formate In methanol; dichloromethane; water at 20℃; for 1 h; Inert atmosphere	Step-2: Synthesis of compound 3: 0 1 3 To a solution of the epoxide .2 (5.03 g, 20 miiiol) in methanol (100 ml), dichloromethane (50 ml) and water (5 ml) at room temperature under nitrogen was added ammonium formate (3.78 g, 60 mmol) followed by 10percent palladium on charcoal (540 nig, 0.51 mmol Pd). The resulting mixture was stirred at room temperature for one hour and then the catalyst was recovered by filtration through celite The filter pad was washed with dichloromethane (20 ml), and the organic phase of the combined filtrate was separated and dried over anhydrous sodium sulphate. Filtration and evaporation of the solvent {rotary evaporator., water aspirator pressure, 40. degree. C.) gave the crude alcohol (3) which was crystallized from ethyl acetate (20 ml) to afford white crystals, 4.7 g, (93percent yield).
93%	With palladium 10% on activated carbon; ammonium formate In methanol; dichloromethane; water at 20℃; for 1 h; Inert atmosphere	To a solution of the epoxide 2 (5.03 g, 20 mmol) in methanol (100 ml), dichloromethane (50 ml) and water (5 ml) at room temperature under nitrogen was added ammonium formate (3.78 g, 60 mmol) followed by 10percent palladium on charcoal (540 mg, 0.51 mmol Pd). The resulting mixture was stirred at room temperature for one hour and then the catalyst was recovered by filtration through celite. The filter pad was washed with dichloromethane (20 ml), and the organic phase of the combined filtrate was separated and dried over anhydrous sodium sulphate. Filtration and evaporation of the solvent (rotary evaporator, water aspirator pressure, 40° C.) gave the crude alcohol (3) which was crystallized from ethyl acetate (20 ml) to afford white crystals, 4.7 g, (93percent yield).
82%	With hydrogen; triethylamine In methanol; water at 50 - 55℃; for 1.66667 h;	Example 2 lOJl-Pihydro-lO-hydroxy-SH-dibenz/bJ/azepine-S-carboxamideO); [45] To 105 g water wet epoxide (i.e. 69.5 g dry) 600 ml methanol and 1.9 ml tri- ethylamine were added. The slurry was stirred for 10 min at 20-30⁰C and then EPO <DP n="11"/>transferred into a 1000 ml stainless steel autoclave and rinsed with 100 ml methanol. A slurry of 0.89 g palladium on charcoal (50percent water wet) in 10 ml water was added. It was rinsed with 10 ml water. After inertisation with nitrogen (3 x) the autoclave was flushed with hydrogen (2 x). The hydrogenation was performed at 10-15 bar H₁ pressure and 50-55⁰C. (1000 rpm, reaction time ca. 70 min.) After complete hydrogen consumption, the reaction mixture was stirred for further 30 min. to ensure complete conversion. The conversion was checked by an in process test (HPLC: epoxide < =1.0percenta/a). The catalyst was removed by filtration and the Filtrate was washed with 80 ml methanol. The filtrate was concentrated in vacuo (70-75 IcPa, 51-61⁰C temperature of the distillate) from about 900 ml to 180-190 ml. The residue was cooled to about 40-45⁰C and 200 ml isopropanol was added. The distillation was repeated (100 IcPA, 70-80⁰C, ca. 145 ml distillate) to remove the methanol completely. The residue was cooled to 0-5⁰C and was stirred at this temperature for at least 2 hours for crystallisation. The precipitate was filtered and washed with 80 ml isopropanol / water (1: 1). The wet product (ca. 68 g) was dried in vacuo to yield 58.8 g racemic alcohol. [Yield 82percent]

63%

With 5%-palladium/activated carbon; hydrogen; triethylamine In methanol; water for 2 h;

the reaction mixture of 55 (252 mg, 1.0 mmol), 10 mg of Pd/C (5percent), triethylamine in MeOH (4.75 mL) / H₂O (0.25 mL) was stirred under H₂ atmosphere (1 bar) for 2h. The catalyst was removed by filtration. After evaporation of the volatile components, the product was obtained by recrystallization of the residue from EtOAc as colorless solid (160 mg,63percent).

Reference： [1] Patent: WO2013/167985, 2013, A1, . Location in patent: Paragraph 00102; 00103
[2] Patent: US2016/122332, 2016, A1, . Location in patent: Paragraph 0123-0124
[3] Patent: WO2006/75925, 2006, A2, . Location in patent: Page/Page column 9-10
[4] Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 3, p. 1077 - 1088

2
[ 791633-38-0 ]
[ 29331-92-8 ]

Yield	Reaction Conditions	Operation in experiment
90%	at 20℃; for 48 h;	A suspension of 10-chloro-10,11-dihydro-5H-dibenz/b,f/azepine-5-carboxamide (VII) (50.0g, 183.5mmol) in de-ionised water (900mL) was stirred at room temperature for forty-eight hours. The solid was removed by filtration and washed with de-ionised water (100mL). After drying at 50C over phosphorus pentoxide under high vacuum until constant weight, there was obtained racemic ()-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide (III) as a beige solid (42.12g, 90percent), of m.p. 186-188 C. Chiral HPLC analysis of this product (LiChroCART 250-4 HPLC Cartridge ChiraDex 5m, (Merck), Flowrate: 0.8mL/min, Mobile Phase: water/methanol 8:2, sample injected was 20L of 0.2mg analyte/mL dissolved in the mobile phase, and UV detection at 210/254nm showed complete racemisation (1:1 mixture of (S)-(+)-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide (I) and (R)-(-)-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide (II), with retention time of (R)-(-)-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide (II) at 8.39 minutes and retention time of (S)-(+)-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide (I) at 9.1 minutes). This intermediate was hydrolysed as described in Example 3 to give the perfectly racemic product () 10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide (III) as judged by chiral HPLC analysis
69%	With water In 1,3-dioxane; water at 50℃; for 0.666667 h;	A stirred suspension of 10-chloro-10,11-dihydro-5H-dibenz/b,f/azepine-5-carboxamide (VII) (7.68g, 28.16mmol) in a mixture of dioxane (40mL) and water (40mL) was stirred at 50C for forty minutes. The organic solvent was then removed by evaporation (40C, water-aspirator pressure) and water (40mL) was added to the residue, which was then extracted with a 10percent isopropanol/dichloromethane solvent mixture. The combined organic extracts were washed with water and brine, then dried over anhydrous magnesium sulphate, filtered and evaporated (40C, water-aspirator pressure) to leave a pale yellowish foam. Recrystallisation from a dichloromethane/isopropanol mixture afforded racemic ()-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide (III) as white crystals (4.92g, 69percent), of m.p. 186.5-188 C. Chiral HPLC analysis of this product (LiChroCART 250-4 HPLC Cartridge ChiraDex 5m, (Merck), Flowrate: 0.8mL/min, Mobile Phase: water/methanol 8:2, sample injected was 20L of 0.2mg analyte/mL dissolved in the mobile phase, and UV detection at 210/254nm showed complete racemisation (1:1 mixture of (S)-(+)-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide (I) and (R)-(-)-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide (II), with retention time of (R)-(-)-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide (II) at 8.39 minutes and retention time of (S)-(+)-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide (I) at 9.1 minutes).

Reference： [1] Patent: EP1477480, 2004, A1, . Location in patent: Page 6, 7
[2] Patent: EP1477480, 2004, A1, . Location in patent: Page 6

3
[ 28721-07-5 ]
[ 29331-92-8 ]

Yield	Reaction Conditions	Operation in experiment
97.3%	With sodium tetrahydroborate In methanol; water at 20 - 45℃; for 1.5 h;	At room temperature,The (100.0g, 0.4mol) oxcarbazepine,400 mL methanol and 200 mL water were added to a 1 L round bottom flask,Sodium borohydride (15.0 g, 0.4 mol) was added portionwise,After stirring at room temperature for 30min, the reaction was continued at 45 ° C for 1h.The reaction is completed,The reaction mixture was concentrated under reduced pressure to 200-300 mL,filter,Washed 3 times,Got pale yellow solid powder 99.0g,For compound 1,Yield 97.3percent.
94%	With sodium tetrahydroborate In ethanol; water at 45 - 50℃;	Sodium borohydride (6.0 g, 0.162 mol) was portion-wise added to the suspension of Azepine amide (45.0 g, 0.178 mol) in Ab. Ethanol (185 ml) and DM water (103 ml) at an ambient temperature. Reaction mixture was allowed to stir for 2-3 hr at 45-50° C. Progress of reaction was monitored by TLC (Solvent system: 10percent Methanol in DCM). After completion of reaction, acetone was slowly added to reaction mixture at 10-15° C. Reaction mixture was further stirred for 30 min. at an ambient temperature. Organic solvents from reaction mixture were distilled off under reduced pressure at 45-50° C. Residue thus obtained was stirred in DM water (100 ml) for 1-2 hr at 0-5° C. Suspension was filtered and washed with ice-cold water (2*25 ml). Air dry the product for 12-15 hr at 50-60° C. to get pure desired compound (42.8 g, 94percent) with 99percent purity by HPLC.
93.8%	With sodium tetrahydroborate; water In methanol at 25 - 65℃; for 2.75 h;	Sodium borohydride (15.6 g, 0.412 mol) was added to a stirred suspension of oxcarbazepine (200 g, 0.793 mol) in a mixture of methanol (400 mL) and water (220 mL) at 25°C to 30°C in three portions at 15 minutes intervals. The reaction mixture was stirred at 60°C to 65°C for 2 hours and cooled to 25°C to 30°C and pH was adjusted to 6.8 to 7.2 using diluted hydrochloric acid (31 mL concentrated hydrochloric acid in 100 mL deionised water). Deionised water (700 mL) was added to the reaction mixture with stirring and was cooled to 0°C to 5°C for 3 hours. The crystalline product was filtered, washed with deionised water (100 mL) and dried at 40°C to 45°C to constant weight to give the titled compound. Yield: 189.1 g (93.8percent) Purity: 99.93percent

93.8%	With sodium tetrahydroborate; water In methanol at 25 - 65℃; for 2.25 h;	Sodium borohydride (15.6 g, 0.412 mol) was added to a stirred suspension of oxcarbazepine (200 g, 0.793 mol) in a mixture of methanol (400 mL) and water (220 mL) at 25° C. to 30° C. in three portions at 15 minutes intervals. The reaction mixture was stirred at 60° C. to 65° C. for 2 hours and cooled to 25° C. to 30° C. and pH was adjusted to 6.8 to 7.2 using diluted hydrochloric acid (31 mL concentrated hydrochloric acid in 100 mL deionised water). Deionised water (700 mL) was added to the reaction mixture with stirring and was cooled to 0° C. to 5° C. for 3 hours. The crystalline product was filtered, washed with deionised water (100 mL) and dried at 40° C. to 45° C. to constant weight to give the titled compound. Yield: 189.1 g (93.8percent) Purity: 99.93percent
2.42 kg	With sodium tetrahydroborate In ethanol at 20℃; for 4.5 h; Large scale	To a 200 L autoclave, oxcarbazepine (2.52 kg, 10 mol)And ethanol (25 L),Stir at room temperature to completely dissolve.Sodium borohydride (0.378 kg, 10 mol) was aliquoted into 5 batches,Each batch of 30 minutes,Add to the above solution with stirring.After the addition is complete, stirring is continued for 2 hours at room temperature.After the reaction was complete, add water (50L)After stirring and adjusting the pH of the reaction solution to 7 with concentrated hydrochloric acid,The precipitated solid was filtered and collected.The filtrate was then concentrated to 50 L and filtered once and the solid was collected.Two batches of solids were combined and dried,2.42 kg of licacizidine (rac) solid was obtained.

Reference： [1] Patent: CN106588773, 2017, A, . Location in patent: Paragraph 0093; 0094; 0095; 0096
[2] Patent: US2016/122332, 2016, A1, . Location in patent: Paragraph 0137-0138
[3] Patent: WO2013/8194, 2013, A2, . Location in patent: Page/Page column 12; 13
[4] Patent: US2015/65704, 2015, A1, . Location in patent: Paragraph 0072
[5] Journal of Medicinal Chemistry, 1999, vol. 42, # 14, p. 2582 - 2587
[6] RSC Advances, 2016, vol. 6, # 101, p. 98730 - 98736
[7] Patent: WO2010/113179, 2010, A2, . Location in patent: Page/Page column 13
[8] Patent: WO2011/91131, 2011, A2, . Location in patent: Page/Page column 39
[9] Patent: WO2011/138795, 2011, A2, . Location in patent: Page/Page column 22
[10] Patent: WO2012/121701, 2012, A1, . Location in patent: Page/Page column 13
[11] Patent: CN106938986, 2017, A, . Location in patent: Paragraph 0028; 0029; 0034; 0035; 0036

4
[ 356760-08-2 ]
[ 29331-92-8 ]

Yield	Reaction Conditions	Operation in experiment
69%	for 0.05 h; Microwave irradiation	EXAMPLE 8; 5 g (21.18 mmol) of 5-cyano-10-hydroxy-10,l l-dihydro-5H-dibenz-[b,f]azepine are dissolved in 20 ml of a water/ethanol 1 : 1 mixture. The resulting mixture is added with 13 g of sodium perborate (84.7 mmol) in small portions, then placed in a microwave oven (Prolabo Synthewave 402) and irradiated for 3 min. at 300 Watt. The reaction mixture is cooled, ethanol is evaporated off under reduced pressure and the resulting liquid is extracted with ethyl acetate (3 x 50 ml). The extracted organic phase is dried over sodium sulfate and concentrated. 3.7 g (69percent yield) are obtained.
69%	With sodium perborate; water In ethanol for 0.05 h; Microwave irradiation	EXAMPLE 8; 5 g (21.18 mmol) of 5-cyano-10-hydroxy-10,11-dihydro-5H-dibenz-[b,f]azepine are dissolved in 20 ml of a water/ethanol 1:1 mixture. The resulting mixture is added with 13 g of sodium perborate (84.7 mmol) in small portions, then placed in a microwave oven (Prolabo Synthewave 402) and irradiated for 3 min. at 300 Watt.The reaction mixture is cooled, ethanol is evaporated off under reduced pressure and the resulting liquid is extracted with ethyl acetate (3.x.50 ml). The extracted organic phase is dried over sodium sulfate and concentrated. 3.7 g (69percent yield) are obtained.
67%	With Oxone; sodium hydroxide; water In acetone for 2 h; Aqueous phosphate buffer; Heating / reflux	EXAMPLE 7; A suspension of 5-cyano-10-hydroxy-10,l l-dihydro-5H-dibenz[b,f]- azepine (8.5 mmol, 2 g) in 30 ml of a phosphate buffer solution pH=7.5 and acetone (10 ml) is added to a freshly prepared solution of oxone (26 g, 42.4 mmol) in 1 : 1 water/acetone (100 ml). During the addition, pH is kept basic by means of a 2N NaOH solution. The reaction mixture is refluxed for approx. 2 hours until total disappearance of the starting product (HPLC). The excess oxone is destroyed with a bisulfite solution, the mixture is extracted with ethyl acetate and dried over magnesium sulfate. The solvent is evaporated off under reduced pressure and the residue is crystallized to afford the desired amide (1.5 g, 67percent yield).

67%	With sodium hydroxide; phosphate buffer; water In acetone for 2 h; Alkaline aqueous solution; Heating / reflux	EXAMPLE 7; A suspension of 5-cyano-10-hydroxy-10,11-dihydro-5H-dibenz[b,f]-azepine (8.5 mmol, 2 g) in 30 ml of a phosphate buffer solution pH=7.5 and acetone (10 ml) is added to a freshly prepared solution of oxone (26 g, 42.4 mmol) in 1:1 water/acetone (100 ml). During the addition, pH is kept basic by means of a 2N NaOH solution. The reaction mixture is refluxed for approx. 2 hours until total disappearance of the starting product (HPLC). The excess oxone is destroyed with a bisulfite solution, the mixture is extracted with ethyl acetate and dried over magnesium sulfate. The solvent is evaporated off under reduced pressure and the residue is crystallized to afford the desired amide (1.5 g, 67percent yield).
66%	at 0℃; for 2 h;	EXAMPLE 6; A suspension of 94 g (0.398 moles) of 5-cyano- 10-hydroxy- 10, l 1- dihydro-5H-dibenz[b,f]azepine in 500 ml of isopropanol is added with 142 g(12 mmol) of potassium tert-butoxide. The suspension is cooled at 0⁰C and300 ml of hydrogen peroxide (35percent solution) are dropped therein in 1 hour atO⁰C, keeping this temperature for one more hour, after which time iodinated EPO <DP n="7"/>starch analysis shows that hydrogen peroxide is no longer present, and HPLC analysis shows the disappearance of the starting product. Isopropanol is evaporated off under reduced pressure, pH is adjusted to approx. 3 with cone. HCl, and the mixture is extracted with ethyl acetate. The organic phase is dried and concentrated to give 96.4 g of a crude which is recrystallyzed from isopropanol to afford 67.1 g of product, 66percent yield.
66%	With potassium <i>tert</i>-butylate; water; dihydrogen peroxide In isopropyl alcohol at 0℃; for 2 h;	EXAMPLE 6; A suspension of 94 g (0.398 moles) of 5-cyano-10-hydroxy-10,11-dihydro-5H-dibenz[b,f]azepine in 500 ml of isopropanol is added with 142 g (12 mmol) of potassium tert-butoxide. The suspension is cooled at 0° C. and 300 ml of hydrogen peroxide (35percent solution) are dropped therein in 1 hour at 0° C., keeping this temperature for one more hour, after which time iodinated starch analysis shows that hydrogen peroxide is no longer present, and HPLC analysis shows the disappearance of the starting product. Isopropanol is evaporated off under reduced pressure, pH is adjusted to approx. 3 with conc. HCl, and the mixture is extracted with ethyl acetate.The organic phase is dried and concentrated to give 96.4 g of a crude which is recrystallized from isopropanol to afford 67.1 g of product, 66percent yield.

Reference： [1] Patent: WO2006/53674, 2006, A2, . Location in patent: Page/Page column 6
[2] Patent: US2008/221320, 2008, A1, . Location in patent: Page/Page column 2
[3] Patent: WO2006/53674, 2006, A2, . Location in patent: Page/Page column 6
[4] Patent: US2008/221320, 2008, A1, . Location in patent: Page/Page column 2
[5] Patent: WO2006/53674, 2006, A2, . Location in patent: Page/Page column 5-6
[6] Patent: US2008/221320, 2008, A1, . Location in patent: Page/Page column 2
[7] Patent: WO2006/53674, 2006, A2, . Location in patent: Page/Page column 2-5
[8] Patent: WO2006/53674, 2006, A2, . Location in patent: Page/Page column 4-5
[9] Patent: WO2006/53674, 2006, A2, . Location in patent: Page/Page column 5
[10] Patent: US2008/221320, 2008, A1, . Location in patent: Page/Page column 1-2
[11] Patent: US2008/221320, 2008, A1, . Location in patent: Page/Page column 2
[12] Patent: US2008/221320, 2008, A1, . Location in patent: Page/Page column 2

5
[ 3564-73-6 ]
[ 28721-07-5 ]
[ 29331-92-8 ]

Reference： [1] European Journal of Organic Chemistry, 2003, # 3, p. 578 - 586

6
[ 298-46-4 ]
[ 29331-92-8 ]

Reference： [1] Patent: WO2013/167985, 2013, A1,
[2] Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 3, p. 1077 - 1088
[3] Patent: US2016/122332, 2016, A1,

7
[ 21737-58-6 ]
[ 29331-92-8 ]

Reference： [1] Patent: US2016/122332, 2016, A1,

8
[ 3564-73-6 ]
[ 29331-92-8 ]

Reference： [1] Bioscience, Biotechnology, and Biochemistry, 1993, vol. 57, # 9, p. 1589 - 1590

[ 29331-92-8 ] Synthesis Path-Downstream 1~71

1
[ 3564-73-6 ]
[ 29331-92-8 ]

Reference： [1]Bioscience, Biotechnology and Biochemistry,1993,vol. 57,p. 1589 - 1590

2
[ 59-67-6 ]
[ 29331-92-8 ]
nicotinic acid 5-carbamoyl-10,11-dihydro-5H-dibenzo[b,f]azepin-10-yl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 2582 - 2587

3
[ 104-01-8 ]
[ 29331-92-8 ]
(4-methoxy-phenyl)-acetic acid 5-carbamoyl-10,11-dihydro-5H-dibenzo[b,f]azepin-10-yl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 2582 - 2587

4
[ 28721-07-5 ]
[ 29331-92-8 ]

Yield	Reaction Conditions	Operation in experiment
97.3%	With sodium tetrahydroborate; In methanol; water; at 20 - 45℃; for 1.5h;	At room temperature,The (100.0g, 0.4mol) oxcarbazepine,400 mL methanol and 200 mL water were added to a 1 L round bottom flask,Sodium borohydride (15.0 g, 0.4 mol) was added portionwise,After stirring at room temperature for 30min, the reaction was continued at 45 C for 1h.The reaction is completed,The reaction mixture was concentrated under reduced pressure to 200-300 mL,filter,Washed 3 times,Got pale yellow solid powder 99.0g,For compound 1,Yield 97.3%.
94%	With sodium tetrahydroborate; In ethanol; water; at 45 - 50℃;	Sodium borohydride (6.0 g, 0.162 mol) was portion-wise added to the suspension of Azepine amide (45.0 g, 0.178 mol) in Ab. Ethanol (185 ml) and DM water (103 ml) at an ambient temperature. Reaction mixture was allowed to stir for 2-3 hr at 45-50 C. Progress of reaction was monitored by TLC (Solvent system: 10% Methanol in DCM). After completion of reaction, acetone was slowly added to reaction mixture at 10-15 C. Reaction mixture was further stirred for 30 min. at an ambient temperature. Organic solvents from reaction mixture were distilled off under reduced pressure at 45-50 C. Residue thus obtained was stirred in DM water (100 ml) for 1-2 hr at 0-5 C. Suspension was filtered and washed with ice-cold water (2*25 ml). Air dry the product for 12-15 hr at 50-60 C. to get pure desired compound (42.8 g, 94%) with 99% purity by HPLC.
93.8%	With sodium tetrahydroborate; water; In methanol; at 25 - 65℃; for 2.75h;	Sodium borohydride (15.6 g, 0.412 mol) was added to a stirred suspension of oxcarbazepine (200 g, 0.793 mol) in a mixture of methanol (400 mL) and water (220 mL) at 25C to 30C in three portions at 15 minutes intervals. The reaction mixture was stirred at 60C to 65C for 2 hours and cooled to 25C to 30C and pH was adjusted to 6.8 to 7.2 using diluted hydrochloric acid (31 mL concentrated hydrochloric acid in 100 mL deionised water). Deionised water (700 mL) was added to the reaction mixture with stirring and was cooled to 0C to 5C for 3 hours. The crystalline product was filtered, washed with deionised water (100 mL) and dried at 40C to 45C to constant weight to give the titled compound. Yield: 189.1 g (93.8%) Purity: 99.93%

93.8%	With sodium tetrahydroborate; water; In methanol; at 25 - 65℃; for 2.25h;	Sodium borohydride (15.6 g, 0.412 mol) was added to a stirred suspension of oxcarbazepine (200 g, 0.793 mol) in a mixture of methanol (400 mL) and water (220 mL) at 25 C. to 30 C. in three portions at 15 minutes intervals. The reaction mixture was stirred at 60 C. to 65 C. for 2 hours and cooled to 25 C. to 30 C. and pH was adjusted to 6.8 to 7.2 using diluted hydrochloric acid (31 mL concentrated hydrochloric acid in 100 mL deionised water). Deionised water (700 mL) was added to the reaction mixture with stirring and was cooled to 0 C. to 5 C. for 3 hours. The crystalline product was filtered, washed with deionised water (100 mL) and dried at 40 C. to 45 C. to constant weight to give the titled compound. Yield: 189.1 g (93.8%) Purity: 99.93%
	With sodium tetrahydroborate; In ethanol; water; at 25 - 45℃;	Oxcarbazepine (50gm, 0.20mol) is suspended in a mixture of water (1 16mL) and ethanol (203mL). Sodium borohydride (5.8 lgm, 0.15mol) is added to this suspension in three equal portions over 15 min at about 25-300C. The temperature of reaction mixture is raised to about 40-450C and continued stirring at about 40-450C for about 3 hours. After completion of the reaction, reaction mixture is cooled to about 10-150C and acetone (43.5mL) is added at about 10-150C. The reaction mixture is concentrated at about 40- 45C under reduced pressure. The residue is triturated with water (125mL) at room temperature to obtain the product as solid. The product is filtered, washed with, water (25mL) and dried at about 40-450C under reduced pressure to get racemic 10,11-Dihydro-10-hydroxy-5H-dibenz[b,fJazepine-5-carboxamide (46.75gm).
		Oxcarbazepine (200 g), ethanol (800 mL) and water (200 mL) are charged into a round-bottom flask and stirred for 5 minutes. Sodium borohydride (24.1 g) is charged slowly to the mixture at 25-35C and stirred for 10 minutes. The mixture is heated to 40-45C and maintained for 2-3 hours. The solvent from the reaction mixture is evaporated completely at 45- 50C. Water (2000 mL) is added to the mass and stirred at 30C for 1-2 hours. The obtained solid is collected by filtration, washed with water (200 mL), and dried at 70C, to afford 190.0 g of the title compound. Purity by HPLC: 99.1 %
	With sodium tetrahydroborate; water; In methanol; at 25 - 60℃; for 7h;Product distribution / selectivity;	Example- 1: Preparation of 10-hydroxy-10,H-dihydro-5H-dibenz[b,fJazepine-5- carboxamide compound of formuIa-4; Sodium borohydride (11.3 g) was added to the solution of 10-oxo-10,l 1-dihydro- 5H-dibenz[b,fJazepine-5-carboxamide compound of formula-2 (50 g) in water (100 ml), followed by methanol (200 ml) at 25-35C. The reaction mixture was heated to 55-60C and then stirred for 7 hours at 55-60C. After completion of the reaction, distilled off methanol completely under reduced pressure and then cooled to 25-30C. Water was added to the reaction mixture and then stirred for 60 minutes at 25-30C. Filtered the solid, washed with water and then dried to get the title compound. Yield: 45 grams
	With sodium tetrahydroborate; In methanol; dichloromethane; at 5 - 30℃;	100 gm of oxcarbazepine and 10.6 gm of sodium borohydride were dissolved in 300 ml of methylene dichloride in a dry round bottom flask. The solution was then cooled to 5-15C. 300 ml of methanol was added to the above solution over 1.0 to 1.5 hours, and the solution was maintained at 20-30C for 1.0 hour. The solution was then distilled under atmospheric condition until 300 ml volume of methanol remained. Next, 500 ml of distilled mineral water at 50C was added to the solution. The solution was cooled to 20-30C and maintained at this temperature for 15-30 minutes. The reaction mass was then filtered and the obtained solid was washed twice with 100 ml of distilled mineral water. The product, namely, (+/-)-10,l l-dihydro-10-hydroxy-5H- dibenz[b,f]azepine-5-carboxamide (step 1 product) was dried in an oven at 70C. The dry weight of the step 1 product was 90 gm (with a chemical purity of 99.4%).
2.42 kg	With sodium tetrahydroborate; In ethanol; at 20℃; for 4.5h;Large scale;	To a 200 L autoclave, oxcarbazepine (2.52 kg, 10 mol)And ethanol (25 L),Stir at room temperature to completely dissolve.Sodium borohydride (0.378 kg, 10 mol) was aliquoted into 5 batches,Each batch of 30 minutes,Add to the above solution with stirring.After the addition is complete, stirring is continued for 2 hours at room temperature.After the reaction was complete, add water (50L)After stirring and adjusting the pH of the reaction solution to 7 with concentrated hydrochloric acid,The precipitated solid was filtered and collected.The filtrate was then concentrated to 50 L and filtered once and the solid was collected.Two batches of solids were combined and dried,2.42 kg of licacizidine (rac) solid was obtained.

Reference： [1]Patent: CN106588773,2017,A .Location in patent: Paragraph 0093; 0094; 0095; 0096
[2]Patent: US2016/122332,2016,A1 .Location in patent: Paragraph 0137-0138
[3]Patent: WO2013/8194,2013,A2 .Location in patent: Page/Page column 12; 13
[4]Patent: US2015/65704,2015,A1 .Location in patent: Paragraph 0072
[5]Journal of Medicinal Chemistry,1999,vol. 42,p. 2582 - 2587
[6]RSC Advances,2016,vol. 6,p. 98730 - 98736
[7]Patent: WO2010/113179,2010,A2 .Location in patent: Page/Page column 13
[8]Patent: WO2011/91131,2011,A2 .Location in patent: Page/Page column 39
[9]Patent: WO2011/138795,2011,A2 .Location in patent: Page/Page column 22
[10]Patent: WO2012/121701,2012,A1 .Location in patent: Page/Page column 13
[11]Patent: CN106938986,2017,A .Location in patent: Paragraph 0028; 0029; 0034; 0035; 0036

5
[ 29331-92-8 ]
[ 13734-41-3 ]
2-tert-butoxycarbonylamino-3-methyl-butyric acid 5-carbamoyl-10,11-dihydro-5H-dibenzo[b,f]azepin-10-yl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 2582 - 2587

6
[ 29331-92-8 ]
[ 20225-24-5 ]
2-ethyl-pentanoic acid 5-carbamoyl-10,11-dihydro-5H-dibenzo[b,f]azepin-10-yl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 2582 - 2587

7
[ 29331-92-8 ]
[ 99-66-1 ]
10-[(2-propyl)pentanoyloxy]-10,11-dihydro-5H-dibenz/b,f/azepine-5-carboxamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 2582 - 2587

8
[ 29331-92-8 ]
[ 104-03-0 ]
10-(4-nitrophenyl)acetoxy-10,11-dihydro-5H-dibenz/b,f/azepine-5-carboxamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 2582 - 2587

9
[ 29331-92-8 ]
[ 14602-86-9 ]
carbonic acid 5-carbamoyl-10,11-dihydro-5H-dibenzo[b,f]azepin-10-yl ester 2-isopropyl-5-methyl-cyclohexyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 2582 - 2587

10
[ 29331-92-8 ]
[ 15356-62-4 ]
(2-isopropyl-5-methyl-cyclohexyloxy)-acetic acid 5-carbamoyl-10,11-dihydro-5H-dibenzo[b,f]azepin-10-yl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 2582 - 2587

11
[ 29331-92-8 ]
[ 51019-44-4 ]
acetoxy-phenyl-acetic acid 5-carbamoyl-10,11-dihydro-5H-dibenzo[b,f]azepin-10-yl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 2582 - 2587

12
[ 29331-92-8 ]
[ 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 [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 2582 - 2587

13
[ 29331-92-8 ]
[ 541-41-3 ]
licarbazepine ethyl carbonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	With pyridine; In dichloromethane; at 20℃; for 1h;	2.54 g (lOmmol) racemic licarbazepine was suspended in a mixture of 75 ml anhydrous dichloromethane and 3 ml pyridine. At ambient temperature a solution of 1 Ag ethylchloro formate (13 mmol) in 5 ml anhydrous dichloromethane was added drop wise. Stirred the reaction mixture for lhr and reaction mixture was quenched with water. The organic phase was washed with sodium hydrogen sulfate solution, water and saturated sodium bicarbonate solution. The organic phase was extracted and dried on sodium sulfate, evaporated the solvent under reduced pressure to give viscous oil. The viscous oil was diluted with diethyl ether to give solidification. The suspension was filtered washed with diethyl ether and dried to give 1.27g white powder (72 %).

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 2582 - 2587
[2]Patent: WO2011/45648,2011,A2 .Location in patent: Page/Page column 25

14
[ 29331-92-8 ]
[ 3282-30-2 ]
2,2-dimethyl-propionic acid 5-carbamoyl-10,11-dihydro-5H-dibenzo[b,f]azepin-10-yl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 2582 - 2587

15
[ 29331-92-8 ]
[ 98-88-4 ]
(RS)-10-benzoyloxy-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 2582 - 2587

16
[ 29331-92-8 ]
[ 802294-64-0 ]
(RS)-10,11-dihydro-10-propionyloxy-5H-dibenz[b,f]azepine-5-carboxamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 2582 - 2587

17
[ 29331-92-8 ]
[ 79-08-3 ]
10-bromoacetoxy-10,11-dihydro-5H-dibenz/b,f/azepine-5-carboxamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 2582 - 2587

18
[ 29331-92-8 ]
[ 75-36-5 ]
Licarbazepine acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine;dmap; In dichloromethane; at 20 - 25℃; for 1h;	Example 5: Preparation of 10-acetoxy- 10,11 -dihydro-5H-dibenz [b,f]azepine-5- carboxamide compound of formula-5; To the 10-hydroxy-10,l l-dihydro-5H-dibenz[b,fJazepine-5-carboxamide compound of formula-4 (10 g) in dichloromethane (100 ml) added diisopropylethylamine (11 ml) and dimethyl aminopyridine (0.5 g) at 20 to 25C. Stirred the reaction mixture for 10 minutes. Added acetyl chloride (3.0 g) to the reaction mixture dropwise at the same temperature. Stirred the reaction mixture for 1 hour at the same temperature. Quenched the reaction mixture with hydrochloric acid and extracted with dichloromethane. Distilled off the solvent completely to get the title compound. Yield: 8.0 grams
2.65 kg	With pyridine; In dichloromethane; at 0 - 25℃; for 5h;Large scale;	Dried licacizal (rac) solid (2.42 kg, 9 mol) in a 200 L reaction kettleWas dissolved in anhydrous dichloromethane (50 L)Additional dry pyridine (2.3 L, 28.5 mol) was added.The solution was cooled to 0 C,Acetyl chloride (0.81 L, 11.4 mol)In anhydrous methylene chloride (10 L)And keep the temperature of the reaction liquid does not exceed 4 .After two hours or so to be added dropwise,Warming to 25 degrees,Continue to stir 3 hours.After the reaction was completed, water (50 L) was added to the reaction solution and the pH of the reaction solution was adjusted to 4-5 with sodium hydroxide. After stirring for half an hour, the reaction solution was allowed to stand still.After completely stratified to collect the methylene chloride layer,Drying under reduced pressure gave 2.67 kg of licacitin acetate (racemic) solid.
	With pyridine; dmap; In dichloromethane; at 0 - 20℃;Inert atmosphere;	(3.0 g, 11.8 mmol) of compound 1,(2.8 g, 18.4 mmol) pyridine,A catalytic amount of DMAP and 50 mL of anhydrous dichloromethane were added to a 100 mL round bottom flask (A);(14.2 mmol) of compound 2 in anhydrous dichloromethane (B) for use.At 0 C,(B) is slowly dropped into (A) under the protection of N2,Dropping is completed,Reaction at room temperature 1-3h.The reaction is completed,To the reaction solution was added 20 mL of water,Stirring 5min,Then washed three times with 10% HCl,Wash with saturated salt once.Drying over anhydrous sodium sulfate overnight,Filter to remove the desiccant,The solvent was distilled off under reduced pressure,Got crude.Column chromatography (methanol / dichloromethane / methylene chloride (v / v) = 1:50 to 1:30) gave a foamy solid,A small amount of ether solidified white solid powder.

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 2582 - 2587
[2]Patent: WO2011/138795,2011,A2 .Location in patent: Page/Page column 23-24
[3]Patent: CN106938986,2017,A .Location in patent: Paragraph 0028; 0030
[4]Patent: CN106588773,2017,A .Location in patent: Paragraph 0098

19
[ 29331-92-8 ]
[ 79-11-8 ]
chloro-acetic acid 5-carbamoyl-10,11-dihydro-5H-dibenzo[b,f]azepin-10-yl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 2582 - 2587

20
[ 29331-92-8 ]
[ 57-11-4 ]
octadecanoic acid 5-carbamoyl-10,11-dihydro-5H-dibenzo[b,f]azepin-10-yl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 2582 - 2587

21
[ 29331-92-8 ]
[ 598-78-7 ]
2-chloro-propionic acid 5-carbamoyl-10,11-dihydro-5H-dibenzo[b,f]azepin-10-yl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 2582 - 2587

22
[ 29331-92-8 ]
[ 5538-51-2 ]
10-(2-acetoxybenzoyloxy)-10,11-dihydro-5H-dibenz/b,f/azepine-5-carboxamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 2582 - 2587

23
[ 29331-92-8 ]
[ 107-92-6 ]
(RS)-10-butyroxy-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 2582 - 2587

25
[ 3564-73-6 ]
[ 28721-07-5 ]
[ 29331-92-8 ]
10,11-dioxo-10,11-dihydro-dibenzo[b,f]azepine-5-carboxylic acid amide [ No CAS ]
10-hydroperoxy-10,11-dihydro-dibenzo[b,f]azepine-5-carboxylic acid amide [ No CAS ]

Reference： [1]European Journal of Organic Chemistry,2003,p. 578 - 586

26
[ 791633-38-0 ]
[ 29331-92-8 ]

Yield	Reaction Conditions	Operation in experiment
90%	With water; at 20℃; for 48h;	A suspension of 10-chloro-10,11-dihydro-5H-dibenz/b,f/azepine-5-carboxamide (VII) (50.0g, 183.5mmol) in de-ionised water (900mL) was stirred at room temperature for forty-eight hours. The solid was removed by filtration and washed with de-ionised water (100mL). After drying at 50C over phosphorus pentoxide under high vacuum until constant weight, there was obtained racemic ()-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide (III) as a beige solid (42.12g, 90%), of m.p. 186-188 C. Chiral HPLC analysis of this product (LiChroCART 250-4 HPLC Cartridge ChiraDex 5m, (Merck), Flowrate: 0.8mL/min, Mobile Phase: water/methanol 8:2, sample injected was 20L of 0.2mg analyte/mL dissolved in the mobile phase, and UV detection at 210/254nm showed complete racemisation (1:1 mixture of (S)-(+)-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide (I) and (R)-(-)-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide (II), with retention time of (R)-(-)-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide (II) at 8.39 minutes and retention time of (S)-(+)-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide (I) at 9.1 minutes). This intermediate was hydrolysed as described in Example 3 to give the perfectly racemic product () 10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide (III) as judged by chiral HPLC analysis
69%	With water; In 1,3-dioxane; water; at 50℃; for 0.666667h;	A stirred suspension of 10-chloro-10,11-dihydro-5H-dibenz/b,f/azepine-5-carboxamide (VII) (7.68g, 28.16mmol) in a mixture of dioxane (40mL) and water (40mL) was stirred at 50C for forty minutes. The organic solvent was then removed by evaporation (40C, water-aspirator pressure) and water (40mL) was added to the residue, which was then extracted with a 10% isopropanol/dichloromethane solvent mixture. The combined organic extracts were washed with water and brine, then dried over anhydrous magnesium sulphate, filtered and evaporated (40C, water-aspirator pressure) to leave a pale yellowish foam. Recrystallisation from a dichloromethane/isopropanol mixture afforded racemic ()-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide (III) as white crystals (4.92g, 69%), of m.p. 186.5-188 C. Chiral HPLC analysis of this product (LiChroCART 250-4 HPLC Cartridge ChiraDex 5m, (Merck), Flowrate: 0.8mL/min, Mobile Phase: water/methanol 8:2, sample injected was 20L of 0.2mg analyte/mL dissolved in the mobile phase, and UV detection at 210/254nm showed complete racemisation (1:1 mixture of (S)-(+)-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide (I) and (R)-(-)-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide (II), with retention time of (R)-(-)-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide (II) at 8.39 minutes and retention time of (S)-(+)-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide (I) at 9.1 minutes).

Reference： [1]Patent: EP1477480,2004,A1 .Location in patent: Page 6, 7
[2]Patent: EP1477480,2004,A1 .Location in patent: Page 6

27
[ 36507-30-9 ]
[ 29331-92-8 ]

Yield	Reaction Conditions	Operation in experiment
93%	With palladium 10% on activated carbon; ammonium formate; In methanol; dichloromethane; water; at 20℃; for 1h;Inert atmosphere;	Step-2: Synthesis of compound 3: 0 1 3 To a solution of the epoxide .2 (5.03 g, 20 miiiol) in methanol (100 ml), dichloromethane (50 ml) and water (5 ml) at room temperature under nitrogen was added ammonium formate (3.78 g, 60 mmol) followed by 10% palladium on charcoal (540 nig, 0.51 mmol Pd). The resulting mixture was stirred at room temperature for one hour and then the catalyst was recovered by filtration through celite The filter pad was washed with dichloromethane (20 ml), and the organic phase of the combined filtrate was separated and dried over anhydrous sodium sulphate. Filtration and evaporation of the solvent {rotary evaporator., water aspirator pressure, 40. degree. C.) gave the crude alcohol (3) which was crystallized from ethyl acetate (20 ml) to afford white crystals, 4.7 g, (93% yield).
93%	With palladium 10% on activated carbon; ammonium formate; In methanol; dichloromethane; water; at 20℃; for 1h;Inert atmosphere;	To a solution of the epoxide 2 (5.03 g, 20 mmol) in methanol (100 ml), dichloromethane (50 ml) and water (5 ml) at room temperature under nitrogen was added ammonium formate (3.78 g, 60 mmol) followed by 10% palladium on charcoal (540 mg, 0.51 mmol Pd). The resulting mixture was stirred at room temperature for one hour and then the catalyst was recovered by filtration through celite. The filter pad was washed with dichloromethane (20 ml), and the organic phase of the combined filtrate was separated and dried over anhydrous sodium sulphate. Filtration and evaporation of the solvent (rotary evaporator, water aspirator pressure, 40° C.) gave the crude alcohol (3) which was crystallized from ethyl acetate (20 ml) to afford white crystals, 4.7 g, (93% yield).
82%	With hydrogen; triethylamine;palladium on activated charcoal; In methanol; water; at 50 - 55℃; under 7500.75 - 11251.1 Torr; for 1.66667h;	Example 2 lOJl-Pihydro-lO-hydroxy-SH-dibenz/bJ/azepine-S-carboxamideO); [45] To 105 g water wet epoxide (i.e. 69.5 g dry) 600 ml methanol and 1.9 ml tri- ethylamine were added. The slurry was stirred for 10 min at 20-300C and then EPO <DP n="11"/>transferred into a 1000 ml stainless steel autoclave and rinsed with 100 ml methanol. A slurry of 0.89 g palladium on charcoal (50% water wet) in 10 ml water was added. It was rinsed with 10 ml water. After inertisation with nitrogen (3 x) the autoclave was flushed with hydrogen (2 x). The hydrogenation was performed at 10-15 bar H1 pressure and 50-550C. (1000 rpm, reaction time ca. 70 min.) After complete hydrogen consumption, the reaction mixture was stirred for further 30 min. to ensure complete conversion. The conversion was checked by an in process test (HPLC: epoxide < =1.0%a/a). The catalyst was removed by filtration and the Filtrate was washed with 80 ml methanol. The filtrate was concentrated in vacuo (70-75 IcPa, 51-610C temperature of the distillate) from about 900 ml to 180-190 ml. The residue was cooled to about 40-450C and 200 ml isopropanol was added. The distillation was repeated (100 IcPA, 70-800C, ca. 145 ml distillate) to remove the methanol completely. The residue was cooled to 0-50C and was stirred at this temperature for at least 2 hours for crystallisation. The precipitate was filtered and washed with 80 ml isopropanol / water (1: 1). The wet product (ca. 68 g) was dried in vacuo to yield 58.8 g racemic alcohol. [Yield 82%]

63%

With 5%-palladium/activated carbon; hydrogen; triethylamine; In methanol; water; under 750.075 Torr; for 2h;

the reaction mixture of 55 (252 mg, 1.0 mmol), 10 mg of Pd/C (5%), triethylamine in MeOH (4.75 mL) / H2O (0.25 mL) was stirred under H2 atmosphere (1 bar) for 2h. The catalyst was removed by filtration. After evaporation of the volatile components, the product was obtained by recrystallization of the residue from EtOAc as colorless solid (160 mg,63%).

Reference： [1]Patent: WO2013/167985,2013,A1 .Location in patent: Paragraph 00102; 00103
[2]Patent: US2016/122332,2016,A1 .Location in patent: Paragraph 0123-0124
[3]Patent: WO2006/75925,2006,A2 .Location in patent: Page/Page column 9-10
[4]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 1077 - 1088

28
[ 356760-08-2 ]
[ 29331-92-8 ]

Yield	Reaction Conditions	Operation in experiment
69%	With sodium perborate; ethanol; water; for 0.05h;Microwave irradiation;Product distribution / selectivity;	EXAMPLE 8; 5 g (21.18 mmol) of 5-cyano-10-hydroxy-10,l l-dihydro-5H-dibenz-[b,f]azepine are dissolved in 20 ml of a water/ethanol 1 : 1 mixture. The resulting mixture is added with 13 g of sodium perborate (84.7 mmol) in small portions, then placed in a microwave oven (Prolabo Synthewave 402) and irradiated for 3 min. at 300 Watt. The reaction mixture is cooled, ethanol is evaporated off under reduced pressure and the resulting liquid is extracted with ethyl acetate (3 x 50 ml). The extracted organic phase is dried over sodium sulfate and concentrated. 3.7 g (69% yield) are obtained.
69%	With sodium perborate; water; In ethanol; for 0.05h;Microwave irradiation;Product distribution / selectivity;	EXAMPLE 8; 5 g (21.18 mmol) of 5-cyano-10-hydroxy-10,11-dihydro-5H-dibenz-[b,f]azepine are dissolved in 20 ml of a water/ethanol 1:1 mixture. The resulting mixture is added with 13 g of sodium perborate (84.7 mmol) in small portions, then placed in a microwave oven (Prolabo Synthewave 402) and irradiated for 3 min. at 300 Watt.The reaction mixture is cooled, ethanol is evaporated off under reduced pressure and the resulting liquid is extracted with ethyl acetate (3×50 ml). The extracted organic phase is dried over sodium sulfate and concentrated. 3.7 g (69% yield) are obtained.
67%	With Oxone; sodium hydroxide; water; In acetone; for 2h;pH 7.5;Aqueous phosphate buffer; Heating / reflux;Product distribution / selectivity;	EXAMPLE 7; A suspension of 5-cyano-10-hydroxy-10,l l-dihydro-5H-dibenz[b,f]- azepine (8.5 mmol, 2 g) in 30 ml of a phosphate buffer solution pH=7.5 and acetone (10 ml) is added to a freshly prepared solution of oxone (26 g, 42.4 mmol) in 1 : 1 water/acetone (100 ml). During the addition, pH is kept basic by means of a 2N NaOH solution. The reaction mixture is refluxed for approx. 2 hours until total disappearance of the starting product (HPLC). The excess oxone is destroyed with a bisulfite solution, the mixture is extracted with ethyl acetate and dried over magnesium sulfate. The solvent is evaporated off under reduced pressure and the residue is crystallized to afford the desired amide (1.5 g, 67% yield).

67%	With sodium hydroxide; phosphate buffer; water; In acetone; for 2h;Alkaline aqueous solution; Heating / reflux;Product distribution / selectivity;	EXAMPLE 7; A suspension of 5-cyano-10-hydroxy-10,11-dihydro-5H-dibenz[b,f]-azepine (8.5 mmol, 2 g) in 30 ml of a phosphate buffer solution pH=7.5 and acetone (10 ml) is added to a freshly prepared solution of oxone (26 g, 42.4 mmol) in 1:1 water/acetone (100 ml). During the addition, pH is kept basic by means of a 2N NaOH solution. The reaction mixture is refluxed for approx. 2 hours until total disappearance of the starting product (HPLC). The excess oxone is destroyed with a bisulfite solution, the mixture is extracted with ethyl acetate and dried over magnesium sulfate. The solvent is evaporated off under reduced pressure and the residue is crystallized to afford the desired amide (1.5 g, 67% yield).
66%	With potassium tert-butylate; water; dihydrogen peroxide; isopropyl alcohol; at 0℃; for 2h;Product distribution / selectivity;	EXAMPLE 6; A suspension of 94 g (0.398 moles) of 5-cyano- 10-hydroxy- 10, l 1- dihydro-5H-dibenz[b,f]azepine in 500 ml of isopropanol is added with 142 g(12 mmol) of potassium tert-butoxide. The suspension is cooled at 00C and300 ml of hydrogen peroxide (35% solution) are dropped therein in 1 hour atO0C, keeping this temperature for one more hour, after which time iodinated EPO <DP n="7"/>starch analysis shows that hydrogen peroxide is no longer present, and HPLC analysis shows the disappearance of the starting product. Isopropanol is evaporated off under reduced pressure, pH is adjusted to approx. 3 with cone. HCl, and the mixture is extracted with ethyl acetate. The organic phase is dried and concentrated to give 96.4 g of a crude which is recrystallyzed from isopropanol to afford 67.1 g of product, 66% yield.
66%	With potassium tert-butylate; water; dihydrogen peroxide; In isopropyl alcohol; at 0℃; for 2h;Product distribution / selectivity;	EXAMPLE 6; A suspension of 94 g (0.398 moles) of 5-cyano-10-hydroxy-10,11-dihydro-5H-dibenz[b,f]azepine in 500 ml of isopropanol is added with 142 g (12 mmol) of potassium tert-butoxide. The suspension is cooled at 0 C. and 300 ml of hydrogen peroxide (35% solution) are dropped therein in 1 hour at 0 C., keeping this temperature for one more hour, after which time iodinated starch analysis shows that hydrogen peroxide is no longer present, and HPLC analysis shows the disappearance of the starting product. Isopropanol is evaporated off under reduced pressure, pH is adjusted to approx. 3 with conc. HCl, and the mixture is extracted with ethyl acetate.The organic phase is dried and concentrated to give 96.4 g of a crude which is recrystallized from isopropanol to afford 67.1 g of product, 66% yield.
	With ethanol; water; dihydrogen peroxide; potassium carbonate; at 0 - 25℃; for 4 - 5h;Product distribution / selectivity;	EXAMPLE 1; 200 g (1.45 moles) of K2CO3 dissolved in 200 ml of water are added with 700 ml of ethanol and 100 g (0.423 moles) of 5-cyano-10-hydroxy-10,l l- dihydro-5H-dibenz[b,f]azepine. The suspension is cooled to O0C and 150 ml EPO <DP n="4"/>(166 g equivalent to 1.47 moles) of a 30% hydrogen peroxide solution are dropped therein in 1 hour at 00C, keeping this temperature for one more hour. The mixture is then slowly warmed to 200C, keeping this temperature for 3 hours. HPLC analysis shows the disappearance of the starting product; iodinated starch analysis shows that hydrogen peroxide is no longer present.The lower aqueous phase is separated and discarded. The ethanol solution is evaporated to dryness under vacuum and the residual suspension is added with 500 ml of water, stirred at 2O0C for 2 hours, then filtered. The residue is washed with water and dried in a static dryer at 700C. 95 g of compound 2 are obtained, with HPLC purity = 95%.30 g of compound 2 are dissolved under reflux in 80 ml of acetone+ 40 ml of water. The reaction is slowly cooled at room temperature, then to00C for 2 hours and filtered, washing with 50 ml of a 1 : 1 acetone/water mixture, then with 50 ml of water. The residue is dried at 700C. 23 g of 2 are obtained, with HPLC purity = 99.1 %.Elemental analysis =Calculated: C 70.85%, H 5.55%, N 11.02%, O 12.58%. Found: C 70.45%, H 5.59%, N 10.93%, O 12.69%.; EXAMPLE 2; 100 g (0.72 moles) Of K2CO3 dissolved in 100 ml of water are added with 500 ml of ethanol and 100 g (0.423 moles) of 5-cyano-10-hydroxy-10, l l - dihydro-5H-dibenz[b,f]azepine. The suspension is cooled at O0C and 80 ml (88.8 g equivalent to 0.78 moles) of a 30% hydrogen peroxide solution are dropped therein in 1 hour keeping this temperature for one more hour. The mixture is then slowly warmed to 200C, keeping this temperature for 3 hours. HPLC analysis shows that the starting product is no longer present.Ethanol is completely removed under vacuum and the residual suspension is added with 500 ml of water, stirred at 200C for 2 hours, then EPO <DP n="5"/>filtered. The residue is washed with water and dried in a static dryer at 70C.97 g of compound 2 are obtained, with HPLC purity = 95.3%.The product is crystallized following the procedure reported in Example 1 to obtain a product with quality comparable to that of the product obtained in Example 1.; EXAMPLE 3; 60 g (0.435 moles) Of K2CO3 dissolved in 120 ml of water are added with 300 ml of ethanol and 100 g (0.423 moles) of 5-cyano-10-hydroxy-10, l l- dihydro-5H-dibenz[b,f]azepine. The suspension is cooled at 1O0C and 80 ml (88.8 g equivalent to 0.78 moles) of a 30% hydrogen peroxide solution are dropped therein in 1 hour, keeping the temperature at 10-20C. Then temperature is kept at 20-25C for 3 hours. HPLC analysis shows that the starting product is no longer present.Ethanol is completely removed under vacuum and the residual suspension is added with 150 ml of water, stirred at 2O0C for 2 hours, then filtered. The residue is washed with water and dried in a static dryer at 700C.98 g of compound 2 are obtained, with HPLC purity = 94.5%.The product is crystallized following the procedure reported in Example 1 to obtain a product with quality comparable to that of the product obtained in Example 1.
	With sodium hydroxide; water; dihydrogen peroxide; isopropyl alcohol; at 0 - 20℃; for 5h;Product distribution / selectivity;	EXAMPLE 4; 10 g (0.1 moles) of a 30% NaOH solution are dropped in 600 ml of isopropanol, then added with 100 g (0.423 moles) of 5-cyano-10-hydroxy- 10, l l-dihydro-5H-dibenz[b,f]azepine. The suspension is cooled at 00C and dropwise added with 80 ml (88.8 g equivalent to 0.78 moles) of a 30% hydrogen peroxide solution in 1 hour at 00C, keeping this temperature for one more hour. The mixture is then slowly warmed to 200C, keeping this temperature for 3 hours. HPLC analysis shows that the starting product is no EPO <DP n="6"/>longer present.The mixture is cooled to 00C and stirred at this temperature for 2 hours, then filtered. The residue is washed with 100 ml of isopropanol at O0C, then dried in a static dryer at 700C. 80 g of product are obtained, with HPLC purity = 97%.This product is crystallized following the procedure reported in Example 1 to obtain a product with quality comparable to that of the product obtained in Example 1.
	With sodium perborate; ethanol; water; at 50℃; for 2h;Product distribution / selectivity;	EXAMPLE 5; A mixture of 400 ml of ethanol and 400 ml of water is added with 100 g(0.423 moles) of 5-cyano-10-hydroxy-10,l l-dihydro-5H-dibenz[b,f]azepine. The suspension is heated to 500C and 100 g of sodium perborate (10% of active oxygen) are added thereto in small portions in 1 hour at this temperature, which is kept for one more hour. HPLC analysis shows that the starting product is no longer present.Ethanol is completely distilled off under vacuum and the suspension is added with 300 ml of water, stirred at 200C for 2 hours, then filtered, washing with 100 ml of water. The residue is dried in a static dryer at 700C. 100 g of compound 2 are obtained, with HPLC purity = 94.3%. The product is crystallized following the procedure reported in Example1 to obtain a product with quality comparable to that of the product obtained in Example 1.
	With water; dihydrogen peroxide; potassium carbonate; In ethanol; at 0 - 20℃; for 5h;Product distribution / selectivity;	EXAMPLE 1; 200 g (1.45 moles) of K2CO3 dissolved in 200 ml of water are added with 700 ml of ethanol and 100 g (0.423 moles) of 5-cyano-10-hydroxy-10,11-dihydro-5H-dibenz[b,f]azepine. The suspension is cooled to 0 C. and 150 ml (166 g equivalent to 1.47 moles) of a 30% hydrogen peroxide solution are dropped therein in 1 hour at 0 C., keeping this temperature for one more hour. The mixture is then slowly warmed to 20 C., keeping this temperature for 3 hours. HPLC analysis shows the disappearance of the starting product; iodinated starch analysis shows that hydrogen peroxide is no longer present.The lower aqueous phase is separated and discarded. The ethanol solution is evaporated to dryness under vacuum and the residual suspension is added with 500 ml of water, stirred at 20 C. for 2 hours, then filtered. The residue is washed with water and dried in a static dryer at 70 C. 95 g of compound 2 are obtained, with HPLC purity=95%.30 g of compound 2 are dissolved under reflux in 80 ml of acetone+40 ml of water. The reaction is slowly cooled at room temperature, then to 0 C. for 2 hours and filtered, washing with 50 ml of a 1:1 acetone/water mixture, then with 50 ml of water. The residue is dried at 70 C. 23 g of 2 are obtained, with HPLC purity=99.1%.Elemental analysis=Calculated: C 70.85%, H 5.55%, N 11.02%, O 12.58%.Found: C 70.45%, H 5.59%, N 10.93%, O 12.69%. EXAMPLE 2; 100 g (0.72 moles) of K2CO3 dissolved in 100 ml of water are added with 500 ml of ethanol and 100 g (0.423 moles) of 5-cyano-10-hydroxy-10,11-dihydro-5H-dibenz[b,f]azepine. The suspension is cooled at 0 C. and 80 ml (88.8 g equivalent to 0.78 moles) of a 30% hydrogen peroxide solution are dropped therein in 1 hour keeping this temperature for one more hour. The mixture is then slowly warmed to 20 C., keeping this temperature for 3 hours. HPLC analysis shows that the starting product is no longer present.Ethanol is completely removed under vacuum and the residual suspension is added with 500 ml of water, stirred at 20 C. for 2 hours, then filtered. The residue is washed with water and dried in a static dryer at 70 C. 97 g of compound 2 are obtained, with HPLC purity=95.3%.The product is crystallized following the procedure reported in Example 1 to obtain a product with quality comparable to that of the product obtained in Example 1. EXAMPLE 3; 60 g (0.435 moles) of K2CO3 dissolved in 120 ml of water are added with 300 ml of ethanol and 100 g (0.423 moles) of 5-cyano-10-hydroxy-10,11-dihydro-5H-dibenz[b,f]azepine. The suspension is cooled at 10 C. and 80 ml (88.8 g equivalent to 0.78 moles) of a 30% hydrogen peroxide solution are dropped therein in 1 hour, keeping the temperature at 10'-20 C. Then temperature is kept at 20'-25 C. for 3 hours. HPLC analysis shows that the starting product is no longer present.Ethanol is completely removed under vacuum and the residual suspension is added with 150 ml of water, stirred at 20 C. for 2 hours, then filtered. The residue is washed with water and dried in a static dryer at 70 C. 98 g of compound 2 are obtained, with HPLC purity=94.5%.The product is crystallized following the procedure reported in Example 1 to obtain a product with quality comparable to that of the product obtained in Example 1.
	With sodium perborate; water; In ethanol; at 50℃; for 2h;Product distribution / selectivity;	EXAMPLE 5; A mixture of 400 ml of ethanol and 400 ml of water is added with 100 g (0.423 moles) of 5-cyano-10-hydroxy-10,11-dihydro-5H-dibenz[b,f]azepine. The suspension is heated to 50 C. and 100 g of sodium perborate (10% of active oxygen) are added thereto in small portions in 1 hour at this temperature, which is kept for one more hour.HPLC analysis shows that the starting product is no longer present. Ethanol is completely distilled off under vacuum and the suspension is added with 300 ml of water, stirred at 20 C. for 2 hours, then filtered, washing with 100 ml of water. The residue is dried in a static dryer at 70 C. 100 g of compound 2 are obtained, with HPLC purity=94.3%.The product is crystallized following the procedure reported in Example 1 to obtain a product with quality comparable to that of the product obtained in Example 1.
	With sodium hydroxide; water; dihydrogen peroxide; In isopropyl alcohol; at 0 - 20℃; for 5h;Product distribution / selectivity;	EXAMPLE 4; 10 g (0.1 moles) of a 30% NaOH solution are dropped in 600 ml of isopropanol, then added with 100 g (0.423 moles) of 5-cyano-10-hydroxy-10,11-dihydro-5H-dibenz[b,f]azepine. The suspension is cooled at 0 C. and dropwise added with 80 ml (88.8 g equivalent to 0.78 moles) of a 30% hydrogen peroxide solution in 1 hour at 0 C., keeping this temperature for one more hour. The mixture is then slowly warmed to 20 C., keeping this temperature for 3 hours. HPLC analysis shows that the starting product is no longer present.The mixture is cooled to 0 C. and stirred at this temperature for 2 hours, then filtered. The residue is washed with 100 ml of isopropanol at 0 C., then dried in a static dryer at 70 C. 80 g of product are obtained, with HPLC purity=97%.This product is crystallized following the procedure reported in Example 1 to obtain a product with quality comparable to that of the product obtained in Example 1.

Reference： [1]Patent: WO2006/53674,2006,A2 .Location in patent: Page/Page column 6
[2]Patent: US2008/221320,2008,A1 .Location in patent: Page/Page column 2
[3]Patent: WO2006/53674,2006,A2 .Location in patent: Page/Page column 6
[4]Patent: US2008/221320,2008,A1 .Location in patent: Page/Page column 2
[5]Patent: WO2006/53674,2006,A2 .Location in patent: Page/Page column 5-6
[6]Patent: US2008/221320,2008,A1 .Location in patent: Page/Page column 2
[7]Patent: WO2006/53674,2006,A2 .Location in patent: Page/Page column 2-5
[8]Patent: WO2006/53674,2006,A2 .Location in patent: Page/Page column 4-5
[9]Patent: WO2006/53674,2006,A2 .Location in patent: Page/Page column 5
[10]Patent: US2008/221320,2008,A1 .Location in patent: Page/Page column 1-2
[11]Patent: US2008/221320,2008,A1 .Location in patent: Page/Page column 2
[12]Patent: US2008/221320,2008,A1 .Location in patent: Page/Page column 2

29
[ 29331-92-8 ]
[ 87-69-4 ]
[ 108-24-7 ]
C₂₃H₂₂N₂O₉ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		L-(+)-Tartaric acid (20gm, 0.13mol) is stirred with acetic anhydride (51.49gm, 0.5mol) and a catalytic quantity of sulphuric acid (96 %) at about 25-3O0C. The reaction is exothermic and the temperature raise to about 60-650C. Thereafter, the reaction mixture is heated to reflux and stirred at reflux temperature for 10 min. The reaction mass is concentrated at about 65-700C under reduced pressure and the remaining residue mass is co-evaporated with toluene (26mL).The residue is dissolved in methylene chloride (277ml) and racemic 10,l l-Dihydro-10- hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (28.2gm, O.l lmol), pyridine (9.57gm, 0.12mol) and 4-dimethylaminopyridine (0.54gm, 0.004mol) are added to the solution. Thereafter, the reaction mixture is stirred at about 25-300C for forty minutes and then water (197mL) is added. The reaction mass is stirred at about 15-200C for about 12 hours. The precipitated solid is filtered, washed with water (2 x 28mL) and dried at 40- 45C under reduced pressure to afford the intermediate, diacetyl tartarate half-ester (26.1gm).

Reference： [1]Patent: WO2010/113179,2010,A2 .Location in patent: Page/Page column 14

30
[ 29331-92-8 ]
[ 4755-77-5 ]
[ 1296102-93-6 ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; In dichloromethane; at 20℃; for 1h;	1.27 g (lOmmol) racemic licarbazepine was suspended in a mixture of 35 ml anhydrous dichloromethane and added 1.5 ml pyridine. At ambient temperature a solution of 1 g of freshly opened ethyl chlorooxalate in 5 ml anhydrous dichloromethane was added drop wise to the above mixture. The reaction mixture was stirred for one hour. The reaction mixture was quenched with water. The organic phase was washed with dilute sodium hydrogen sulfate solution, water and saturated sodium bicarbonate solution. The organic extract was dried on sodium sulfate and evaporated under reduced pressure to give viscous oil. The viscous oil was dissolved with diethyl ether to give solidification. The suspension was filtered, washed with diethyl ether and dried to give desired product

Reference： [1]Patent: WO2011/45648,2011,A2 .Location in patent: Page/Page column 25

31
[ 29331-92-8 ]
[ 38870-89-2 ]
[ 1296102-92-5 ]

Yield	Reaction Conditions	Operation in experiment
95%	With pyridine;dmap; In dichloromethane; at 20℃;	2.54 g (lOmmol) racemic licarbazepine was suspended in a mixture of 50ml anhydrous dichloromethane and 3 ml pyridine. A trace amount (ca 2Qmg) of dimethylaminopyridine (DMAP) was added. At ambient temperature a solution of 1.2 g methoxy acetyichloride (l lmmol) in 5 ml anhydrous dichloromethane was added dropwise. Stirred the reaction mass and added 0.1 g additional methoxyacetyl chloride, the mixture was stirred for 20 min, and then quenched the reaction mass with water. The organic phase was washed with dilute hydrochloric acid (75 ml), water and saturated sodium bicarbonate solution. The organic phase was extracted and dried on sodium sulfate, evaporated the solvent under reduces pressure to give 3.3 g of colorless foam. Further, added methyl tertiary butyl ether to give solidification. The suspension was filtered and air- dried to give a white solid (3.1g; 95%).HPLC: 98% purity

Reference： [1]Patent: WO2011/45648,2011,A2 .Location in patent: Page/Page column 24; 25

32
[ 29331-92-8 ]
[ 104746-03-4 ]

Reference： [1]Patent: WO2011/45648,2011,A2
[2]Patent: WO2011/117885,2011,A1

33
[ 29331-92-8 ]
[ 104746-04-5 ]

Reference： [1]Patent: WO2011/45648,2011,A2
[2]Patent: WO2011/117885,2011,A1
[3]Patent: WO2011/138795,2011,A2
[4]Patent: WO2012/121701,2012,A1
[5]Patent: WO2012/121701,2012,A1
[6]Patent: WO2013/8194,2013,A2
[7]Patent: WO2013/167985,2013,A1
[8]Patent: US2015/65704,2015,A1
[9]Patent: US2016/122332,2016,A1

34
[ 29331-92-8 ]
eslicarbazepine acetate [ No CAS ]

Reference： [1]Patent: WO2011/45648,2011,A2
[2]Patent: WO2011/117885,2011,A1
[3]Patent: WO2011/138795,2011,A2
[4]Patent: WO2011/138795,2011,A2
[5]Patent: WO2012/121701,2012,A1
[6]Patent: WO2012/121701,2012,A1
[7]Patent: WO2013/8194,2013,A2
[8]Patent: WO2013/8194,2013,A2
[9]Patent: WO2013/8194,2013,A2
[10]Patent: WO2013/167985,2013,A1
[11]Patent: US2015/65704,2015,A1
[12]Patent: US2015/65704,2015,A1
[13]Patent: CN106938986,2017,A
[14]Patent: CN106938986,2017,A
[15]Patent: US2016/122332,2016,A1

35
[ 29331-92-8 ]
[ 1296102-94-7 ]

Reference： [1]Patent: WO2011/45648,2011,A2

36
[ 29331-92-8 ]
[ 1296102-97-0 ]

Reference： [1]Patent: WO2011/45648,2011,A2

37
[ 29331-92-8 ]
[ 22204-53-1 ]
[10(R)-5-carbamoyl-10,11-dihydro-5H-dibenz[b,f]azepin-10-yl]-2(S)-methyl-(6-methoxynaphthalen-2-yl)ethanoate [ No CAS ]
[ 1315465-66-7 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; dicyclohexyl-carbodiimide; In dichloromethane; at 30℃;Product distribution / selectivity;	Racemic (+/-)-10, 11 -dihydro-10-hydroxy-5H- dibenz[b,f]azepine-5-carboxamide (100 g), dichloromethane (500 mL) and naproxen (108.69 g) are charged into a round-bottom flask and stirred for 5 minutes. Dicyclohexylcarbodiimide ("DCC", 105.7 g) and 1-hydroxybenzotriazole (OmicronBetaTau, 5.5 g) are added to the mixture. The reaction mixture is maintained at 30C for 7-8 hours, then filtered and the solid washed with dichloromethane (300 mL). The filtrate is evaporated completely under reduced pressure. Ethyl acetate (1800 mL) is added to the mass and stirred at 29C for 15-20 minutes. The mixture is heated to reflux temperature and maintained for 50-60 minutes. The solid obtained is collected by filtration, washed with ethyl acetate (360 mL) and dried at 70C to afford 24.9 g of naproxen ester of (S)-(+)-10, 1 1-dihydro-10- hydroxy-5H-dibenz[b,f]azepine-5-carboxamide. Purity by HPLC: 91.8%; choral purity by HPLC: 93.9%.

Reference： [1]Patent: WO2011/91131,2011,A2 .Location in patent: Page/Page column 39-40

38
[ 29331-92-8 ]
[ 7322-88-5 ]
[ 1335227-38-7 ]

Yield	Reaction Conditions	Operation in experiment
	With dicyclohexyl-carbodiimide;dmap; In dichloromethane; for 1h;Reflux;	Example 4 - Preparation of (10R)-10-[(2S)-(acetyIoxy)(phenyl)ethanoate]-10,ll- dihydro-5H-dibenzo[b,f]azepine-5-carboxamide (VII )Dichloromethane 4800 ml, 366.57 g (S)-(+)-acetyl mandelic acid, 400 g racemic licarbazepine, 192.2 g 4-dimethylaminopyrimidine and 389.51 gdicyclohexylcarbodiimide were mixed in a round bottom flask and the resultant reaction mixture was refluxed for one hour. After completion of reaction the reaction mixture was filtered and the filtrate was washed with aqueous acetic acid and aqueous sodium bicarbonate solution. The organic layer was collected and it was. concentrated. To the residue thus obtained 3600 ml of methyl isobutylketone was added. The resultant reaction mixture was heated at 60 - 65 C for one hour and filtered at the same temperature. The solid thus obtained was again purified by using methylisobutylketone at 60 - 65 C to get title compound with 97.5 % of optical purity.

Reference： [1]Patent: WO2011/117885,2011,A1 .Location in patent: Page/Page column 11

39
[ 29331-92-8 ]
[ 51019-43-3 ]
[ 1335227-37-6 ]

Yield	Reaction Conditions	Operation in experiment
	With dicyclohexyl-carbodiimide;dmap; In dichloromethane; for 1h;Reflux;	Example 1 - Preparation of (10S)-10-[(2R)-(acetyIoxy)(phenyl)ethanoate]-10,ll- dihydro-5H-dibenzo[b,f] azepine -5-carboxamide (VIII)Dichloromethane 2160 ml, 164.96 g (R)-(-)-acetyl mandelic acid, 180 g racemic licarbazepine, 86.48 g 4-dimethylamino pyrimidine and 175.28g dicyclohexylcarbodiimide were mixed in a round bottom flask and the resultant reaction mixture was refluxed for one hour. After completion of reaction the reaction mixture was filtered and the filtrate was -washed with aqueous acetic acid and aqueous sodium bicarbonate solution. The organic layer was collected and it was concentrated. To the residue thus obtained 1620ml of methyl isobutylketone was added. The resultant reaction mixture was heated at 60 - 65 C for one hour and filtered at the same temperature. The solid thus obtained was again purified by. using methyl isobutylketone at 60 - 65 C to get title compound with 97.6% of optical purity.
	With dmap; dicyclohexyl-carbodiimide; In dichloromethane; for 1h;Reflux;	Step-4: Synthesis of compound 4: {00105} Dichloromethane 2160 nil, 164.96 g (R)-(~}~aeet l mandeic acid, 180 g racemic 3, 86.48 g 4-dimethyIamino pyriraidine and l ?5,28g dicydohexy I carbodiimide were mixed in a round bottom flask and the resultant reaction .mixture was refluxed for one hour. After completion of reaction the reaction mixture was filtered and the filtrate was - washed with aqueous acetic acid and aqueous sodium bicarbonate solution. The organic layer was collected and it was concentrated. To the residue thus obtained 1620ml of methyl isobuty'lketone was added. The resultant reaction mixture was heated at 60 - 65 "C for one hour and filtered at the same temperature. The solid thus obtained was again purified by. using methyl isobutylketone at 60 - 65 C to get title compound with 97.6% of optical purity
	With dmap; dicyclohexyl-carbodiimide; In dichloromethane; for 1h;Reflux;	0126) Dichloromethane 2160 ml, 164.96 g (R)-(-)-acetyl mandelic acid, 180 g racemic 3, 86.48 g 4-dimethylamino pyrimidine and 175.28 g dicyclohexylcarbodiimide were mixed in a round bottom flask and the resultant reaction mixture was refluxed for one hour. After completion of reaction the reaction mixture was filtered and the filtrate was washed with aqueous acetic acid and aqueous sodium bicarbonate solution. The organic layer was collected and it was concentrated. To the residue thus obtained 1620 ml of methyl isobutylketone was added. The resultant reaction mixture was heated at 60-65 C. for one hour and filtered at the same temperature. The solid thus obtained was again purified by using methyl isobutylketone at 60-65 C. to get title compound with 97.6% of optical purity.

Reference： [1]Patent: WO2011/117885,2011,A1 .Location in patent: Page/Page column 10
[2]Patent: WO2013/167985,2013,A1 .Location in patent: Paragraph 00104; 00105
[3]Patent: US2016/122332,2016,A1 .Location in patent: Paragraph 0125-0126

40
[ 29331-92-8 ]
(+)-Licarbazepine acetate [ No CAS ]

Reference： [1]Patent: WO2011/117885,2011,A1

41
[ 29331-92-8 ]
[ 2935-35-5 ]
[ 1346462-63-2 ]

Yield	Reaction Conditions	Operation in experiment
	With dicyclohexyl-carbodiimide;dmap; In dichloromethane; at 0 - 35℃; for 5.16667h;	Example 12: Preparation of (S)-((S)-5-carbamoyl-10,ll-dihydro-5H-dibenzo [b,fj azepin-10-yI) 2-amino-2-phenylacetate compound of formula-9a.; 10-hydroxy-10,l l-dihydro-5H-dibenz[b,fJazepine-5-carboxamide compound of formula-4 (1 g) was added to a solution of (S)-2-amino-2-phenyl acetic acid compound of formula-8a (0.62 g) in dichloro methane (10 ml), followed by dimethylamino pyridine (0.12 g) and then cooled to 0-5C. Dicyclohexylcarbodiimide (1.269 g) was added to the reaction mixture and stirred for 10 minutes, Further the reaction mixture temperature was raised to 25-35C and stirred for 5 hours at 25-35C. After completion of the reaction, the reaction mixture was cooled to 0-5C. Filtered the reaction mixture to remove the undissolved product and washed with dichloro methane. The obtained filtrate was washed with 10% sodium bicarbonate solution, followed by water. Distilled off dichloromethane completely under reduced pressure and then added cyclohexane, further the reaction mixture was stirred for 1 hour at 25-35C. Filtered the solid and washed with cyclohexane. To the obtained solid further added water and stirred for 1 hour at 25-35C. Filtered the solid, washed with water and then dried to get the title compound. The obtained compound was further recrystallized twice from isopropyl alcohol to get the pure title compound. Yield: 6 grams; Purity by HPLC: 98%.

Reference： [1]Patent: WO2011/138795,2011,A2 .Location in patent: Page/Page column 26

42
[ 29331-92-8 ]
[ 56080-99-0 ]
[ 1346462-62-1 ]

Yield	Reaction Conditions	Operation in experiment
	With dicyclohexyl-carbodiimide;dmap; In dichloromethane; at 0 - 35℃; for 5.16667h;	Example 2: Preparation of (R)-((S)-5-carbamoyl-10,ll-dihydro-5H-dibenzo[b,fJ azepin- 10-y 1) 1 -benz lpy rrolidine-2-carboxy late (Formula-7a); 10-hydroxy-10,l l-dihydro-5H-dibenz[b,fJazepine-5-carboxamide compound of formula-4 (11.79 g) was added to a solution of N-benzyl-D-proline compound of formula- 6a (10 g) in dichloro methane (100 ml), followed by dimethylamino pyridine (1.49 g) and then cooled to 0-5C. Dicyclohexylcarbodiimide (15.1 g) was added to the reaction mixture and stirred for 10 minutes, Further the reaction mixture temperature was raised to 25-35C and stirred the reaction mixture for 5 hours at 25-35C. After completion of the reaction, the reaction mixture was cooled to 0-5C. Filtered the reaction mixture to remove the undissolved product and washed with dichloro methane. The obtained filtrate was washed with 10% sodium bicarbonate solution, followed by water. Distilled off dichloromethane from organic layer under reduced pressure and then cyclohexane was added to the obtained residue. The reaction mixture was stirred for 1 hour at 25-35C. Filtered the solid and washed with cyclohexane. The wet compound was slurred in water for 1 hour at 25-35C. Filtered the solid, washed with water and then dried to get the title compound. The obtained compound was further recrystallized twice from isopropyl alcohol to get the pure title compound. Yield: 6 grams; Purity by HPLC: 98%.

Reference： [1]Patent: WO2011/138795,2011,A2 .Location in patent: Page/Page column 22-23

43
[ 29331-92-8 ]
[ 31795-93-4 ]
[ 1346462-64-3 ]

Yield	Reaction Conditions	Operation in experiment
	With dicyclohexyl-carbodiimide;dmap; In dichloromethane; at 0 - 5℃;	Example 13: Preparation of (S)-((S)-5-carbamoyl-10,ll-dihydro-5H-dibenzo[b,fJ azepin-10-yl) l-benzylpyrrolidine-2-carboxylate compound of formula-7b.; 10-hydroxy-10,l l-dihydro-5H-dibenz[b,fjazepine-5-carboxamide compound of formula-4 (16.85 g) was added to a solution of <strong>[31795-93-4]N-benzyl-L-proline</strong> (17 g) in dichloro methane (170 ml), followed by dimethylamino pyridine (1 g) at 0-5C. Dicyclohexylcarbodiimide (51.3 g) was added to the reaction mixture and stirred for 60 minutes. The unwanted solid was removed by filtration, and washed with dichloromethane and the filtrate was extracted with aqueous hydrochloric acid. The pH of the aqueous layer was adjusted to 7.0 with 10% sodium bicarbonate solution. The aqueous layer was extracted twice with dichloromethane and distilled off the solvent completely under reduced pressure to get the residue. The obtained residue was recrystallized thrice with ethylacetate and then dried to get pure title compound. Yield: 5.5 grams.

Reference： [1]Patent: WO2011/138795,2011,A2 .Location in patent: Page/Page column 26-27

44
[ 29331-92-8 ]
[ 13734-34-4 ]
[ 1399078-93-3 ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; dicyclohexyl-carbodiimide; In dichloromethane; at 5 - 10℃; for 6h;Product distribution / selectivity;	Example 11:Preparation of N-Boc-protected phenylalanine ester of licarbazapine A solution of N-Boc phenylalnine (15 gm) and triethyl amine (11.9 gm) in dichloromethane (60 mL) was cooled to 0-5C. To the resulting solution pivaloyl chloride (6.5 mL) was added at same temperature. The reaction mass was stirred for 1 h at 20-25C and then filtered. Thus obtained filtrate was added to a solution of licarbazepine, pyridine (5.5 g), dimethylaminopyridine (1 gm) in dichloromethane (60 mL) at 20-25C. Reaction mass was stirred for 3-4 h and washed with 2% sodium bicarbonate solution (50 mL). The solvent was distilled to obtain the title compound.Example 9:Preparation of isobutyloxycarbonyl protected phenylalanine ester of licarbazapineA solution of (l-chlorocarbonyl-2-phenyl-ethyl)-carbamic acid isobutyl ester (5 gm), obtained solution in dichloromethane was added to a solution of licarbazepine (4 gm), pyridine (2.2 mL), dimethylaminopyridine (0.05 gm) and dichloromethane (60 mL) at 5-10C. Reaction mass was stirred at room temperature for 4 h and washed with water. The solvent was distilled to obtain the title compound.
		Example 11 Preparation of N-Boc-Protected Phenylalanine Ester of Licarbazapine A solution of N-Boc phenylalnine (15 gm) and triethyl amine (11.9 gm) in dichloromethane (60 mL) was cooled to 0-5 C. To the resulting solution pivaloyl chloride (6.5 mL) was added at same temperature. The reaction mass was stirred for 1 h at 20-25 C. and then filtered. Thus obtained filtrate was added to a solution of licarbazepine, pyridine (5.5 g), dimethylaminopyridine (1 gm) in dichloromethane (60 mL) at 20-25 C. Reaction mass was stirred for 3-4 h and washed with 2% sodium bicarbonate solution (50 mL). The solvent was distilled to obtain the title compound.

Reference： [1]Patent: WO2012/120356,2012,A2 .Location in patent: Page/Page column 26
[2]Patent: US2013/345198,2013,A1 .Location in patent: Paragraph 0162

45
[ 29331-92-8 ]
[ 1399078-90-0 ]
[ 1399078-91-1 ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; dmap; In dichloromethane; at 5 - 20℃; for 4h;	Example 9:Preparation of isobutyloxycarbonyl protected phenylalanine ester of licarbazapineA solution of (l-chlorocarbonyl-2-phenyl-ethyl)-carbamic acid isobutyl ester (5 gm), obtained solution in dichloromethane was added to a solution of licarbazepine (4 gm), pyridine (2.2 mL), dimethylaminopyridine (0.05 gm) and dichloromethane (60 mL) at 5-10C. Reaction mass was stirred at room temperature for 4 h and washed with water. The solvent was distilled to obtain the title compound.
	With pyridine; dmap; In dichloromethane; at 5 - 20℃; for 4h;	A solution of (1-chlorocarbonyl-2-phenyl-ethyl)-carbamic acid isobutyl ester (5 gm), obtained solution in dichloromethane was added to a solution of licarbazepine (4 gm), pyridine (2.2 mL), dimethylaminopyridine (0.05 gm) and dichloromethane (60 mL) at 5-10 C. Reaction mass was stirred at room temperature for 4 h and washed with water. The solvent was distilled to obtain the title compound.

Reference： [1]Patent: WO2012/120356,2012,A2 .Location in patent: Page/Page column 25
[2]Patent: US2013/345198,2013,A1 .Location in patent: Paragraph 0160

46
[ 29331-92-8 ]
[ 51146-56-6 ]
10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide ibuprofen ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; dicyclohexyl-carbodiimide; In dichloromethane; at 0 - 30℃;	25 gm of the step 1 product, 22.3 gm of S-ibuprofen, and 1.2 gm dimethylaminopyridine(DMAP) were dissolved in 100 ml of methylene dichloride, stirred and cooled to 0-10C. 22.3 gm dicyclohexylcarbodiimide (DCC) was dissolved in 50 ml of methylene dichloride and added to the above solution over 30 minutes. The reaction temperature was raised to 20-30C and maintained at this temperature until the reaction was completed. The reaction mass was filtered and washed with 50 ml of methylene dichloride. The reaction mass was then washed twice with 50 ml of 0.5N HC1, followed by two washes with 50 ml of saturated sodium bicarbonate solution. The solution was then subjected to distillation where the methylene dichloride was distilled off and the resulting slurry was washed with 50 ml of hexane and filtered. The product, namely, the racemic mixture of SS and SR ibuprofen diastereomer esters of 10,l l-dihydro-10- hydroxy-5H-dibenz[b,f]azepine-5-carboxamide (step 2 product) was dried in an oven at 60-65C. The dry weight of the step 2 product was 40.5 gm (with a chemical purity of 50:50 of the R:S esters).

Reference： [1]Patent: WO2012/121701,2012,A1 .Location in patent: Page/Page column 13-14

47
[ 29331-92-8 ]
[ 115588-20-0 ]
10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide ibuprofen ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; triethylamine; In dichloromethane; at 0 - 30℃;	225 gm of the step 1 product, 10.7 gm dimethylaminopyridine (DMAP) and 184 ml of triethylamine were dissolved in 1225 ml of methylene dichloride, stirred and cooled to 5-15C. Ibuprofen acid chloride was added to the reaction mass at 5-15C over a period of from 60 to 90 minutes and maintained for 15-30 minutes at 5-15C. The reaction mass temperature was raised to 20-30C. The reaction mass was then washed twice with 750ml of 0.2M sulfuric acid solution and 750ml of DM water. The solution was then subjected to distillation where the methylene dichloride was distilled off, stripped with hexane and the resulting slurry was washed with 225 ml of hexane and filtered. The product, namely, the racemic mixture of SS and SR ibuprofen diastereomer esters of 10,l l-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide was dried in an oven at 60-65C. The dry weight was 358.9 gm (with a chemical purity of 48.71 :50.17 ofthe R:S esters).

Reference： [1]Patent: WO2012/121701,2012,A1 .Location in patent: Page/Page column 15-16

48
[ 29331-92-8 ]
(S,S)-10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide ibuprofen ester [ No CAS ]

Reference： [1]Patent: WO2012/121701,2012,A1
[2]Patent: WO2012/121701,2012,A1

49
[ 29331-92-8 ]
[ 28721-07-5 ]

Yield	Reaction Conditions	Operation in experiment
90%	With peracetic acid; potassium dichromate; hydrogen; In 1,2-dichloro-ethane; at 20℃; for 1h;	Peroxyaceticacid (1.5 mL, 35% in acetic acid) was added dropwise to a suspension of licarbazepine (56, 508 mg, 2.00 mmol) and K2Cr2O7 (23.3 mg, 0.08 mmol) in 5mL of dichloroethane. The reaction mixture was stirred at room temperature for 1 h. The aqueous solution of Na2SO3 (5%) was added to the reaction mixture before stirred overnight. The organic phase was separated. The aqueous phase was extracted with dichloromethane (2 × 50mL). The combined organic phase was washed with brine, and dried with MgSO4. Evaporation of the solvent gave the product as colorless solid (453 mg, 90%).
65.5%	With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; In dichloromethane; at 25 - 30℃; for 0.25h;	To a stirred suspension of 10-hydroxy-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide (2.0 g, 0.0078 mol) in dichloromethane (10 mL), TEMPO (13 mg, 0.000078) was charged at 25 C. to 30 C. After stirring at 25 C. to 30 C. for 15 minutes, the reaction mixture was cooled to 0 C. to 5 C. and sodium hypochlorite solution (12.0 mL) (adjusted pH=9.7 using 10% aqueous NaHCO3) was charged dropwise. The reaction mixture was stirred at 0 C. to 5 C. for 1 hour. The organic layer was separated and washed with deionised water (20 mL) and concentrated at about 40 C. to 45 C. under reducing pressure. The solid was stirred with toluene (5 mL) and filtered. The solid obtained was stirred with dimethylformamide (12 mL) at 60 C. to 65 C. After stirring at 60 C. to 65 C. for 15 minutes, the reaction mixture was cooled to 20 C. to 25 C. Deionised water (72 mL) was charged and the mixture was further stirred for 30 minutes. The solid was filtered, washed with deionised water (10 mL) and dried at 60 C. to 65 C. under vacuum for 8 hours to obtain the titled compound. Yield: 1.3 g (65.5%) [0106] Chemical Purity: 90.4%
1.3 g		To a stirred suspension of 10-hydroxy-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide (2.0 g, 0.0078 mol) in dichloromethane (10 mL), TEMPO (13 mg, 0.000078) was charged at 25C to 30C. After stirring at 25C to 30C for 15 minutes, the reaction mixture was cooled to 0C to 5C and sodium hypochlorite solution (12.0 mL) (adjusted pH= 9.7 using 10% aqueous NaHCOs) was charged dropwise. The reaction mixture was stirred at 0C to 5C for 1 hour. The organic layer was separated and washed with deionised water (20 mL) and concentrated at about 40C to 45C under reducing pressure. The solid was stirred with toluene (5 mL) and filtered. The solid obtained was stirred with dimethylformamide (12 mL) at 60C to 65C. After stirring at 60C to 65C for 15 minutes, the reaction mixture was cooled to 20C to 25C. Deionised water (72 mL) was charged and the mixture was further stirred for 30 minutes. The solid was filtered, washed with deionised water (10 mL) and dried at 60C to 65C under vacuum for 8 hours to obtain the titled compound. Yield: 1.3 g (65.5%) Chemical Purity: 90.4%

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 1077 - 1088
[2]Patent: US2015/65704,2015,A1 .Location in patent: Paragraph 0105
[3]Patent: WO2013/8194,2013,A2 .Location in patent: Page/Page column 22; 23

50
[ 29331-92-8 ]
[ 6283-74-5 ]
[ 475674-43-2 ]

Yield	Reaction Conditions	Operation in experiment
88.9%		Pyridine (21 g, 0.265 mol) and 4-dimethylaminopyridine (0.86 g, 0.007 mol) were added to a stirred suspension of racemic 10-hydroxy- 10,11-dihydro-5H- dibenzo[b,f]azepine-5-carboxamide (45 g, 0.177 mol) in dichloromethane (450 mL) at 25C to 30C. After stirring at 25C to 30C for 15 minutes, diacetyl-L-tartaric acid anhydride (47.8 g, 0.221 mol) was added to the mixture. The reaction mixture was stirred at 25C to 30C for 2 hours whereupon deionised water (315.0 mL) was added dropwise and the resulting reaction mixture was stirred for 4 hours at 15C to 20C. The precipitated solid was filtered off, washed with deionised water (45 mL) and dried at 50C to 55C to constant weight to obtain the titled compound. Yield: 37 g (88.9%, based on single diastereisomer) Chiral Purity: 90.7%

Reference： [1]Patent: WO2013/8194,2013,A2 .Location in patent: Page/Page column 12

51
[ 29331-92-8 ]
[ 6283-74-5 ]
[ 104746-03-4 ]
[ 104746-04-5 ]

Yield	Reaction Conditions	Operation in experiment
		Pyridine (1.1 mL, 0.0126 mol) was added to a stirred suspension of racemic 10-hydroxy-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide (2.0 g, 0.0079 mol) and ethyl acetate (20 mL) at 30C to 35C. After stirring at 25C to 30C for 15 minutes, diacetyl-L-tartaric acid anhydride (2.72 g, 0.0126 mol) was added to the mixture. The reaction mixture was stirred at 30C to 35C for 1 hour whereupon deionised water (20 mL) was added dropwise and the resulting reaction mixture was stirred for 30 minutes at 0C to 5C. The precipitated solid was filtered off, washed with deionised water (10 mL) and dried at 60C for 4 hours to obtain (10S)-10-hydroxy-10,11-dihydro-5H- dibenzo[b,f]azepine-5-carboxamide tartarate (Yield: 1.6 g, 86.48%, based on single diastereisomer). 3N aqueous sodium hydroxide (4.8 mL) was added dropwise to a stirred suspension of (10S)-10-hydroxy-10,l l-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide tartarate (1.2 g, 0.00255 mol) and methanol (6.0 mL) at 25C to 30C for 15 minutes. The reaction mixture was stirred at 25C to 30C for 1 hour. The precipitated sodium bitartarate was filtered and washed with methanol (10 mL). The filtrate was concentrated at about 40C to 45C under reducing pressure. The reaction mixture was cooled to 25C to 30C and deionised water (10 mL) was added to it. The resulting solution was stirred at 0C to 5C for 30 minutes. The precipitated solid was filtered off, washed with deionised water (10 mL) and dried at 60C for 4 hours to obtain the titled compound. Yield: 0.7 g (77.08%) Chiral Purity: 89.17%

Reference： [1]Patent: WO2013/8194,2013,A2 .Location in patent: Page/Page column 13

52
[ 29331-92-8 ]
C₂₀H₁₉ClN₂O₅ [ No CAS ]

Reference： [1]Patent: WO2013/167985,2013,A1
[2]Patent: US2016/122332,2016,A1

53
[ 29331-92-8 ]
C₂₈H₃₂N₂O₇S₂ [ No CAS ]

Reference： [1]Patent: WO2013/167985,2013,A1
[2]Patent: US2016/122332,2016,A1

54
[ 298-46-4 ]
[ 29331-92-8 ]

Reference： [1]Patent: WO2013/167985,2013,A1
[2]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 1077 - 1088
[3]Patent: US2016/122332,2016,A1

55
[ 29331-92-8 ]
[ 104746-03-4 ]
[ 104746-04-5 ]

Reference： [1]Chirality,2013,vol. 25,p. 897 - 903
[2]RSC Advances,2016,vol. 6,p. 98730 - 98736
[3]RSC Advances,2016,vol. 6,p. 98730 - 98736
[4]RSC Advances,2016,vol. 6,p. 98730 - 98736

56
[ 29331-92-8 ]
[ 1548175-75-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 1077 - 1088

57
[ 29331-92-8 ]
[ 6283-74-5 ]
(10S)-10-hydroxy-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide tartarate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88.9%		Pyridine (21 g, 0.265 mol) and 4-dimethylaminopyridine (0.86 g, 0.007 mol) were added to a stirred suspension of racemic 10-hydroxy-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide (45 g, 0.177 mol) in dichloromethane (450 mL) at 25 C. to 30 C. After stirring at 25 C. to 30 C. for 15 minutes, diacetyl-L-tartaric acid anhydride (47.8 g, 0.221 mol) was added to the mixture. The reaction mixture was stirred at 25 C. to 30 C. for 2 hours whereupon deionised water (315.0 mL) was added dropwise and the resulting reaction mixture was stirred for 4 hours at 15 C. to 20 C. The precipitated solid was filtered off, washed with deionised water (45 mL) and dried at 50 C. to 55 C. to constant weight to obtain the titled compound. Yield: 37 g (88.9%, based on single diastereisomer) Chiral Purity: 90.7%.

Reference： [1]Patent: US2015/65704,2015,A1 .Location in patent: Paragraph 0074

58
[ 21737-58-6 ]
[ 29331-92-8 ]

Reference： [1]Patent: US2016/122332,2016,A1

59
[ 29331-92-8 ]
[ 108-24-7 ]
Licarbazepine acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	With pyridine; dmap; In dichloromethane; at 20℃; for 0.5h;	To the suspension of hydroxy azepine amide (40 g, 0.157 mol) in DCM (340 mL) was added pyridine (18.64 g, 0.235 mol) followed by DMAP (1.92 g, 0.0157 mol) at an ambient temperature. Acetic anhydride (20 g, 0.196 mol) was dropwise added to the reaction mixture at an ambient temperature. The reaction mixture was allowed to stir for 30 mins at the same temperature. Progress of reaction was monitored by TLC (Solvent system: 50% Ethyl acetate in hexane). After completion of reaction, 15% aq. HCl (400 ml) was slowly added to reaction mixture. The organic layer was separated and concentrated under reduced pressure at 40-45 C. The crude residue was purified using Di-isopropyl ether (150 ml) to provide the desired compound as off-white powder (45 g, 96%) with 99.03% purity by HPLC.
4.6 kg	With triethylamine; In dichloromethane;	Raw materials for the 5kg oxcarbazepine,With 0.756kg sodium borohydride reaction,4.4 kg after drying the productRikacapine (racemic);4.4 kg of licacitin (racemic) and 3 L of triethylamine were dissolved in 40 L of anhydrous methylene chloride,Slowly add 2 L of acetic anhydride.After the esterification reaction to obtain licarcastipine (racemic) 4.6kg;10g of lipase freeze-dried powder and 4.6kg of licacitin acetate (racemic) in water and methylene chloride in two-phase solution was stirred under hydrolysis reaction,Keep the reaction temperature at 30 CKeep the reaction solution pH at 7-8.After the reaction, a mixture of (R) -lycarbazepine and eslizarone acetate was obtained,After drying dissolved in anhydrous dichloromethane,Add 3 kg of triphenylphosphine and 0.6 L of acetic acid,0.2 L diisopropyl azodicarboxylate was slowly added with stirring.After the reaction,To obtain the final product of alexidine isoproterenol 4.3kg,[alpha] D 25 = 21.6 (c = 1, pyridine),The total yield from the starting material was 74%99% purity by HPLC,Enantiomeric excess ee> 99%.

Reference： [1]Patent: US2016/122332,2016,A1 .Location in patent: Paragraph 0139-0140
[2]RSC Advances,2016,vol. 6,p. 98730 - 98736
[3]Patent: CN106938986,2017,A .Location in patent: Paragraph 0034; 0035; 0036

60
[ 29331-92-8 ]
5-[(chloroacetyl)carbamoyl]-10,11-dihydro-5H-dibenzo[b,f]azepin-10-yl acetate [ No CAS ]

Reference： [1]Patent: US2016/122332,2016,A1

61
[ 29331-92-8 ]
CLX-SYN-G₄-C₀₂ [ No CAS ]

Reference： [1]Patent: US2016/122332,2016,A1

62
[ 29331-92-8 ]
[ 769-78-8 ]
(S)-10-benzoyloxy-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide [ No CAS ]
(R)-10-benzoyloxy-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide [ No CAS ]
[ 104746-04-5 ]

Reference： [1]RSC Advances,2016,vol. 6,p. 98730 - 98736

63
[ 29331-92-8 ]
[ 769-78-8 ]
(S)-10-benzoyloxy-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide [ No CAS ]
(R)-10-benzoyloxy-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide [ No CAS ]
[ 104746-03-4 ]
[ 104746-04-5 ]

Reference： [1]RSC Advances,2016,vol. 6,p. 98730 - 98736

64
[ 108-05-4 ]
[ 29331-92-8 ]
[ 104746-03-4 ]
[ 104746-04-5 ]
(+)-Licarbazepine acetate [ No CAS ]
eslicarbazepine acetate [ No CAS ]

Reference： [1]RSC Advances,2016,vol. 6,p. 98730 - 98736

65
[ 29331-92-8 ]
[ 105-38-4 ]
(R)-10,11-dihydro-10-propionyloxy-5H-dibenz[b,f]azepine-5-carboxamide [ No CAS ]
(S)-10,11-dihydro-10-propionyloxy-5H-dibenz[b,f]azepine-5-carboxamide [ No CAS ]
[ 104746-03-4 ]
[ 104746-04-5 ]

Reference： [1]RSC Advances,2016,vol. 6,p. 98730 - 98736

66
[ 29331-92-8 ]
[ 123-20-6 ]
(S)-10-butyroxy-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide [ No CAS ]
(R)-10-butyroxy-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide [ No CAS ]
[ 104746-03-4 ]
[ 104746-04-5 ]

Reference： [1]RSC Advances,2016,vol. 6,p. 98730 - 98736

67
[ 29331-92-8 ]
[ 123-62-6 ]
(RS)-10,11-dihydro-10-propionyloxy-5H-dibenz[b,f]azepine-5-carboxamide [ No CAS ]

Reference： [1]RSC Advances,2016,vol. 6,p. 98730 - 98736

68
[ 106-31-0 ]
[ 29331-92-8 ]
(RS)-10-butyroxy-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide [ No CAS ]

Reference： [1]RSC Advances,2016,vol. 6,p. 98730 - 98736

69
[ 29331-92-8 ]
[ 93-97-0 ]
(RS)-10-benzoyloxy-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide [ No CAS ]

Reference： [1]RSC Advances,2016,vol. 6,p. 98730 - 98736

70
[ 29331-92-8 ]
[ 104746-03-4 ]
eslicarbazepine acetate [ No CAS ]

Reference： [1]Patent: CN106938986,2017,A

71
[ 29331-92-8 ]
[ 6283-74-5 ]
C₁₉H₁₈N₂O₇ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
42.5%		Compound (3) (48.0 g, 0.22 mol) was added to 500 mL of dichloromethane and stirred for 2 min,Then (50.8 g, 0.2 mol) compound 1 was added,(17.5 g, 0.22 mol) pyridine,(1.0 g, 8.0 mmol) DMAP,After stirring for 1h at room temperature, 350mL of water was added and stirring was continued for 12h.The reaction was filtered to precipitate,50mL water wash 3 times,After drying to give compound 4,32.82g,Yield 42.5%

Reference： [1]Patent: CN106588773,2017,A .Location in patent: Paragraph 0131

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Similarity: 0.93

[ 3564-73-6 ]

10,11-Dihydro-5H-dibenzo[b,f]azepine-5-carboxamide

Similarity: 0.83

[ 28721-09-7 ]

10-Methoxy-5H-dibenzo[b,f]azepine-5-carboxamide

Similarity: 0.75

[ 85095-61-0 ]

N,N'-(Methylenebis(4,1-phenylene))bis(2,2-dimethylhydrazinecarboxamide)

Similarity: 0.65

[ 159857-79-1 ]

Val-Cit-PAB-OH

Similarity: 0.63

Amines

[ 36507-30-9 ]

1aH-Dibenzo[b,f]oxireno[2,3-d]azepine-6(10bH)-carboxamide

Similarity: 0.93

[ 3564-73-6 ]

10,11-Dihydro-5H-dibenzo[b,f]azepine-5-carboxamide

Similarity: 0.83

[ 28721-09-7 ]

10-Methoxy-5H-dibenzo[b,f]azepine-5-carboxamide

Similarity: 0.75

[ 85095-61-0 ]

N,N'-(Methylenebis(4,1-phenylene))bis(2,2-dimethylhydrazinecarboxamide)

Similarity: 0.65

[ 17274-64-5 ]

1-(4-Aminoindolin-1-yl)ethanone

Similarity: 0.63

Related Parent Nucleus of
[ 29331-92-8 ]

Other Aromatic Heterocycles

[ 36507-30-9 ]

1aH-Dibenzo[b,f]oxireno[2,3-d]azepine-6(10bH)-carboxamide

Similarity: 0.93

[ 3564-73-6 ]

10,11-Dihydro-5H-dibenzo[b,f]azepine-5-carboxamide

Similarity: 0.83

[ 4014-77-1 ]

10,11-Dihydro-5H-dibenzo[b,f]azepin-10-ol

Similarity: 0.77

[ 28721-09-7 ]

10-Methoxy-5H-dibenzo[b,f]azepine-5-carboxamide

Similarity: 0.75

[ 41921-63-5 ]

4,5-Dihydro-1H-benzo[d][1,3]diazepin-2(3H)-one

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Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
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. 29331-92-8 ] {[proInfo.proName]}

Quality Control of [ 29331-92-8 ]

Related Doc. of [ 29331-92-8 ]

Product Details of [ 29331-92-8 ]

Calculated chemistry of [ 29331-92-8 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 29331-92-8 ]

Application In Synthesis of [ 29331-92-8 ]

[ 29331-92-8 ] Synthesis Path-Upstream 1~8

[ 29331-92-8 ] Synthesis Path-Downstream 1~71

Related Functional Groups of [ 29331-92-8 ]

Alcohols

Amides

Ureas

Amines

Related Parent Nucleus of [ 29331-92-8 ]

Other Aromatic Heterocycles

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 29331-92-8 ]

Related Parent Nucleus of
[ 29331-92-8 ]