[ CAS No. 6136-68-1 ] {[proInfo.proName]}

Name: 6136-68-1|3-Acetylbenzonitrile|98%
Brand: Ambeed
SKU: A790566
Price: 9.0 USD
Availability: InStock
Rating: 98 (40 reviews)

,{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]}

2D 3D

Structure of 6136-68-1 * Storage: {[proInfo.prStorage]}

Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

For Research Only 110K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 6136-68-1 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 6136-68-1 ]

SDS Specification

Alternatived Products of [ 6136-68-1 ]

Product Details of [ 6136-68-1 ]

CAS No. :	6136-68-1	MDL No. :	MFCD00001806
Formula :	C₉H₇NO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	SBCFGFDAZCTSRH-UHFFFAOYSA-N
M.W :	145.16	Pubchem ID :	80222
Synonyms :

Calculated chemistry of [ 6136-68-1 ]

Physicochemical Properties

Num. heavy atoms :	11
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.11
Num. rotatable bonds :	1
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	41.35
TPSA :	40.86 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.36 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.57
Log Po/w (XLOGP3) :	1.16
Log Po/w (WLOGP) :	1.76
Log Po/w (MLOGP) :	1.08
Log Po/w (SILICOS-IT) :	2.14
Consensus Log Po/w :	1.54

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-1.81
Solubility :	2.26 mg/ml ; 0.0155 mol/l
Class :	Very soluble
Log S (Ali) :	-1.61
Solubility :	3.54 mg/ml ; 0.0244 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.8
Solubility :	0.232 mg/ml ; 0.0016 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.31

Safety of [ 6136-68-1 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302+H312+H332-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 6136-68-1 ]

* 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 [ 6136-68-1 ]
Downstream synthetic route of [ 6136-68-1 ]

[ 6136-68-1 ] Synthesis Path-Upstream 1~2

1
[ 6136-68-1 ]
[ 105-58-8 ]
[ 62088-13-5 ]

Yield	Reaction Conditions	Operation in experiment
96%	With hydrogenchloride In tetrahydrofuran; mineral oil	Part A. Preparation of ethyl 3-(3-cyanophenyl)-3-oxopropionate. To a suspension of sodium hydride (1.2 g of 60percent suspension in mineral oil, hexane-washed, 30.3 mmol) in 40 mL of tetrahydrofuran was added diethyl carbonate (3.7 mL, 30.3 mmol) and 3-acetyl benzonitrile (2.2 g, 15.2 mmol). The resulting suspension was stirred at 65° C for 1 h and then was cooled to room temperature. There was added 40 mL of 10percent aqueous HCl and the reaction mixture was diluted with ethyl acetate and the layers were separated. The organic layer was washed with brine, dried (MgSO₄) and concentrated in vacuo to afford 3.2 g (96percent) of the title compound, which was sufficiently pure to be used without purification. MS (NH₃-CI) 218.3 (M+H)+.
96%	With hydrogenchloride In tetrahydrofuran; mineral oil	Part A. Preparation of ethyl 3-(3-cyanophenyl)-3-oxopropionate. To a suspension of sodium hydride (1.2 g of 60percent suspension in mineral oil, hexane-washed, 30.3 mmol) in 40 mL of tetrahydrofuran was added diethyl carbonate (3.7 mL, 30.3 mmol) and 3-acetyl benzonitrile (2.2 g, 15.2 mmol). The resulting suspension was stirred at 65° C. for 1 h and then was cooled to room temperature. There was added 40 mL of 10percent aqueous HCl and the reaction mixture was diluted with ethyl acetate and the layers were separated. The organic layer was washed with brine, dried (MgSO₄) and concentrated in vacuo to afford 3.2 g (96percent) of the title compound, which was sufficiently pure to be used without purification. MS (NH₃-CI) 218.3 (M+H)+.

Reference： [1] Journal of Medicinal Chemistry, 2006, vol. 49, # 6, p. 1910 - 1915
[2] Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 5, p. 641 - 645
[3] Patent: WO2011/46774, 2011, A1, . Location in patent: Page/Page column 16
[4] Patent: EP946528, 2003, B1,
[5] Patent: US6187797, 2001, B1,

2
[ 6136-68-1 ]
[ 21860-07-1 ]

Reference： [1] Chemische Berichte, 1900, vol. 33, p. 3409

[ 6136-68-1 ] Synthesis Path-Downstream 1~64

1
[ 6136-68-1 ]
[ 586-42-5 ]

Yield	Reaction Conditions	Operation in experiment
92%		6M Sodium hydroxide (25 mL) was added to 3-acetylbenzonitrile (850 mg, 5.82 mmol) in methanol (25 mL) and then heated at [90C] overnight. After concentrating the reaction mixture, the aqueous layer was washed with dichloromethane (2x), then acidified [PH-3] with 12M HC1. The precipitate was extracted with ethyl acetate then washed with water and saturated brine, dried over anhydrous sodium sulfate filtered and concentrated to afford 3-ethylbenzoic acid as a colorless oil; 0.800g (92%). 1H NMR [(CDC13)] 8 [(PPM)] : 8.70 (s, 2H), 8.33 (d, 2H), 8. 24 (d, 2H), 7.64 (t, 1H), 2.70 (s, 3H).
	In hydrogenchloride;	Step a. 3-[5'-(Adamantan-1-yloxymethyl)-2'cyclohexyl-1H,1H'-[2,4']biimidazolyl-4-yl]-benzoic Acid 3-Acetylbenzoic acid. 3-Acetylbenzonitrile (2.32 g, 16 mmol) was heated under reflux in 6M hydrochloric acid (25 ml) for 7 h. The mixture was cooled and the precipitate filtered, washed with water, and dried in vacuo. Yield 2.36 g (90%). 1H NMR (300 MHz, DMSO) 13.25 (1H, br s), 8.44 (1H, s), 8.18 (2H, m), 7.66 (1H, t), 2.62 (3H, s).

Reference： [1]Patent: WO2004/14881,2004,A2 .Location in patent: Page 138
[2]Chemische Berichte,1900,vol. 33,p. 3409
[3]Patent: US2003/199565,2003,A1

2
[ 6136-68-1 ]
[ 105802-54-8 ]

Yield	Reaction Conditions	Operation in experiment
	With selenium(IV) oxide; In 1,4-dioxane; water; for 12h;Reflux;	To a stirred mixture of SeO2 (20 mmol, 2.2 g) in dioxane (20 mL) was added water (2 mL) and heated toreflux until SeO2 was dissolved. Compound 1a (10 mmol, 1.45 g) was added and the mixture wasstirred at reflux overnight. After completion, the mixture was filtered through a pad of celite. Thefiltrate was concentrated in vacuo. Compound 3-(2-oxoacetyl)benzonitrile was obtained and useddirectly in next step without further purification. To a suspension of alpha-aminoacetamide hydrochloride(1.5 g, 14 mmol) in MeOH (12.5 mL)-water (3.1 mL) was added 12.5 M aqueous NaOH (1.65 mL, 20mmol) solution at -30 C, and then a solution of NaOH (543 mg, 14 mmol) in MeOH (6.1 mL) wasadded to the mixture. A solution of 3-(2-oxoacetyl)benzonitrile in MeOH (11.1 mL) was added to themixture at -20C, and then the resulting suspension was stirred for 2h at same temperature, and thestirring continued for 1 h at room temperature. After cooling with ice water, the mixture was acidifiedwith AcOH. Collection of the resulting precipitates by filtration gave 2a (52%) as a red solid:

Reference： [1]Chemical Communications,1996,p. 1249 - 1250
[2]Patent: US2641601,1950,
[3]Molecules,2019,vol. 24

3
[ 6136-68-1 ]
[ 50916-55-7 ]

Yield	Reaction Conditions	Operation in experiment
2.22 g (55%)	With bromine; In dichloromethane; water;	Example 10 Synthesis of alpha-Bromo-3-cyanoacetophenone (Compound 10) A solution of bromine (0.92 mL, 17.9 mmol) in 8 mL dichloromethane was added to 3-cyanoacetophenone (2.60 g, 17.9 mmol) in 11 mL dichloromethane over 10 min at 5-10 C. The mixture was warmed to room temperature and stirred for 1 hour. Water (25 mL) was added to the mixture. The organic layer was separated, dried over Na2 SO4, and concentrated to a yellow solid (3-50 g). The yellow solid was recrystallized from 95% EtOH to afford compound 10 as white crystals. Yield: 2.22 g (55%). The properties of alpha-bromo-3-cyanoacetophenone are listed below: 1 H NMR (CDCl3, 300 MHz) delta 8.08 (m,2H), 7.81 (m, 2H), 4.43 (s, 2H). 13 C NMR (CDCl3, 75 MHz, APT) delta 189.58 (C), 136.77 (CH), 134.71 (C), 132.66 (CH), 130.02 (CH), 117.69 (C), 113.53 (C), 30.07 (CH2).
	With copper(ll) bromide; In ethyl acetate; for 2h;Heating / reflux;	i) Production of 3-(bromoacetyl)benzonitrile <strong>[6136-68-1]3-Acetylbenzonitrile</strong> (5.33 g) and copper(II) bromide (16.40 g) were suspended in ethyl acetate (100 ml) and the mixture was heated under reflux for 2 hrs. After cooling the reaction mixture, the insoluble material was filtered off and the filtrate was washed with aqueous sodium hydrogen carbonate and saturated brine. The organic layer was dried and concentrated and the residue was recrystallized from ethyl acetate-diisopropyl ether to give the title compound (4.29 g) as colorless powder crystals. 1H-NMR (CDCl3)delta: 2.82 (2H, s), 6.06 (1H, t, J=7.8 Hz), 6.29 (1H, d, J=7.8 Hz), 6.57 - 6.72 (2H, m). IR (KBr): 3104, 2942, 2230, 1709, 1599 cm-1.
	With bromine; In diethyl ether; at 20℃; for 4h;	Br2 (1 mmol) was dropwise added to a solution of 3-acetylbenzonitrile (1 mmol) in Et2O (15 ml) at 0 C., and then the mixture was stirred at r.t. for 4 h. Water was added, and the mixture was extracted with EtOAc. The organic layer was dried over Na2SO4, and was concentrated to give an oil, i.e., 3-(2-bromoacetyl)benzonitrile, which was directly used for the next step without purification.

	With bromine; In diethyl ether; at 0 - 20℃; for 4h;	Br2 (l ml) was dropwise added to a solution of 3-acetylbenzonitrile (2.9 g) in Et20 (100 ml) at 0 C , and then the mixture was stirred at room temparature for 4 h. Water was added, and then the mixture was extracted with EtOAc. The organic layer was dried over Na2S04, and concentrated to give an oil, i.e., 3-(2-bromoacetyl)benzonitrile, which was directly used for the next step without purification.
	With copper(ll) bromide; In chloroform; ethyl acetate;Reflux;	Example 15; Ar-(4-(3-cyanophenyl)-5-(4-(trifluoromethy])phenoxy)thiazol-2-y])-2-(4- (ethylsulfonyl)phenyI)acetamide; Step 1:; To a solution of 3-acetylbenzonitrile (8 g) in chloroform (50 mL) and ethyl acetate (50 mL) was added copper(II) bromide (25.9 g). The reaction mixture was refluxed overnight. Solid was removed by filtration, and the filtrate was washed with sat. ammonium chloride and brine, dried, and concentrated to give 3-(2-bromoacetyl)benzonitrile (13 g) as a yellow oil. MS(ES?) m/z 225 (MH?).
	With copper(ll) bromide; In 2-methyltetrahydrofuran; at 20℃; for 24h;	General procedure: To a solution of acetophenones 1-6 (16.65 mmol) in 2-Metetrahydrofuran(20 mL), copper(II)bromide (19.98 mmol)was added (Raghunath et al. 2015). The reaction mixturewas allowed to stir at room temperature for 24 h. Aftercompletion of the reaction (monitored by TLC), reactionmixture was filtered off. The filtrate containing the 2-bromo-1-phenylethanones 7-12 was taken to the next stepwithout isolation. However, to check the purity of theformed phenacyl bromides, two representative compounds(8 and 10) were isolated in standard procedure by evaporatingthe solvent under vacuum and confirmed by spectralanalysis (1H NMR, Mass, and HPLC). As all the derivativeswere pure by TLC, they were preceded to next step withoutpurification/isolation.

Reference： [1]Bulletin de la Societe Chimique de France,1948,p. 593,596
[2]Journal of Heterocyclic Chemistry,1992,vol. 28,p. 2025 - 2028
[3]Journal of Physical Chemistry,1995,vol. 99,p. 8190 - 8195
[4]Journal of Medicinal Chemistry,1998,vol. 41,p. 2390 - 2410
[5]Bioorganic and medicinal chemistry letters,2002,vol. 12,p. 1511 - 1515
[6]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 3081 - 3085
[7]Patent: US5668165,1997,A
[8]Patent: EP1348706,2003,A1 .Location in patent: Page/Page column 73
[9]Patent: US2009/118292,2009,A1 .Location in patent: Page/Page column 27
[10]Patent: WO2011/137587,2011,A1 .Location in patent: Page/Page column 53
[11]Patent: WO2012/100734,2012,A1 .Location in patent: Page/Page column 24
[12]Medicinal Chemistry Research,2019,vol. 28,p. 1461 - 1470

4
[ 32024-15-0 ]
[ 6136-68-1 ]
[ 33083-94-2 ]

Reference： [1]Journal of the Indian Chemical Society,1971,vol. 48,p. 483 - 489

5
[ 6136-68-1 ]
[ 55805-06-6 ]

Yield	Reaction Conditions	Operation in experiment
76%	With (bis-(2-methoxyethyl)amino)sulfur trufluoride; In ethanol; dichloromethane; at 55℃;	Place 3-acetylbenzonitrile (5.0 g, 34.4 mmol) into a 50 mL polypropylene screw cap tube. Add dichloromethane (17 mL), (bis(2-methoxyethyl)amino)sulfur trifluoride (15.2 g, 69 mmol), and ethanol (200 muL). Purge with nitrogen and heat at 55 0C with stirring overnight. Cool the reaction to room temperature, add the reaction carefully into saturated NaHCO3 with rapid stirring, extract with dichloromethane, dry over magnesium sulfate and evaporate to an oil. Purify the product over silica with 10% Et2theta:hexanes. Evaporate to afford 3-(l,l-difluoro-ethyl)-benzonitrile as a colorless liquid. (4.4 g, 76%), 1H NMR (400 MHz, CDCl3): delta 7.77 (s, IH), 7.70 (t, J= 7.3 Hz, 2H), 7.53 (t, J= 7.9 Hz, IH), 1.94-1.85 (m, 3H).
	With (bis-(2-methoxyethyl)amino)sulfur trufluoride; at 85℃;	a) 3-(1,1-Difluoro-ethyl)-benzonitrile 3-Acetyl benzonitrile (2.9 g, 20 mmol) and deoxo-fluor (5.52 mL, 30 mmol) is stirred overnight at 85 C. The mixture is basified with saturated NaHCO3 and is extracted with CH2Cl2 (3*30 ml). The combined organic phases are washed with brine, dried over Na2SO4, filtered and evaporated. The title compound is obtained after distillation (bp0.85 61 C.) as a colorless syrup: ESIMS [M-CN]+=143; 19F-NMR (376 MHz, CDCl3): delta -88 (s, 2F); 1H-NMR (400 MHz, CDCl3): delta 7.80 (s, 1H), 7.73 (t, 1H), 7.56 (t, 1H), 1.93 (t, 3H).

Reference： [1]Patent: WO2009/131814,2009,A2 .Location in patent: Page/Page column 39
[2]Tetrahedron,1975,vol. 31,p. 391 - 401
[3]Patent: US2009/54427,2009,A1 .Location in patent: Page/Page column 10

6
[ 64-17-5 ]
[ 6136-68-1 ]
[ 60694-93-1 ]

Reference： [1]Journal of Heterocyclic Chemistry,1992,vol. 28,p. 2025 - 2028
[2]Journal of Medicinal Chemistry,1993,vol. 36,p. 46 - 54

7
[ 6136-68-1 ]
[ 153994-67-3 ]

Yield	Reaction Conditions	Operation in experiment
12%		9.40 g (64.757 mmol) 3-cyano-acetophenone, 40.00 g (518.941 mmol) ammonium acetate and 10.00 g (186.951 mmol) ammonium chloride are placed in methanol. The mixture is stirred for 16 hours at 40 C. 2.90 g (46.149 mmol) sodium cyanoborohydride are added, then the mixture is stirred for another 16 hours. The reaction mixture is adjusted to pH3 with glacial acetic acid, then the methanol is evaporated down. On cooling a precipitate settles out. This is suction filtered. The filtrate is made alkaline with conc. sodium hydroxide solution, the precipitate thus formed is suction filtered. The filtrate is extracted with diethyl ether, the combined organic phases are dried and evaporated to dryness. The residue is purified by vacuum distillation. Yield: 1.10 g (=12% of theoretical)

Reference： [1]Journal of the American Chemical Society,1990,vol. 112,p. 5741 - 5747
[2]Patent: US2006/116370,2006,A1 .Location in patent: Page/Page column 8

8
[ 6136-68-1 ]
[ 107-21-1 ]
[ 149917-32-8 ]

Yield	Reaction Conditions	Operation in experiment
79%		Example 1.1.49: (3-(2-methyl-l,3-dioxolan-2-yl)phenyl)methanamine; A stirred solution of 3-acetylbenzonitrile (1.05 g, 7.2 mmol), ethylene glycol (0.81 rnL, 14.5 mmol) and TsOH (0.65 g, 7.2 mmol) was heated at reflux with a Dean-Stark for 15 h during which time the reaction became dark brown suspension. The reaction mixture was cooled to room temperature and diluted with saturated aqueous NaHCO3. The layers were separated and the aqueous layer was extracted with EtOAc (2x20 mL). The combined organic layer was washed with brine, dried with Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (10% EtOAc in hexanes) to provide 3- (2-methyl-l,3-dioxolan-2-yl)benzonitrile (1.08 g, 79%).
76%	With toluene-4-sulfonic acid; In benzene; at 110℃; for 4h;	3-(2-Methyl-1, 3-dioxolan-2-yl)benzonitrile (19): To the mixture of ethylene glycol (0.22 mL, 4 mmol), 3-acetylbenzonitrile 18 (300 mg, 2.04 mmol) and benzene (10 mL) in a Dean-Stark apparatus was added a catalytic amount of p-TSA (0.1 equiv). The reaction mixture was heated at 110 C for 4 h. The benzene was removed under reduced pressure and the residue was purified by column chromatography using ethylacetate-hexane as an eluent to give 19 (293 mg, 76%). ?H NMR (CDC13, 400 MHz) oe 2.62 (s, 4H), 7.59 (t, J = 7.6 Hz, 1H), 7.82 (d, J 7.6 Hz, 1H)), 8.15 (d, J= 8 Hz, 1H), 8.21 (s, 1H).

Reference： [1]Journal of Medicinal Chemistry,2000,vol. 43,p. 3315 - 3321
[2]Journal of Medicinal Chemistry,2008,vol. 51,p. 6318 - 6333
[3]Patent: WO2009/42694,2009,A1 .Location in patent: Page/Page column 93
[4]Journal of Medicinal Chemistry,2012,vol. 55,p. 7759 - 7771
[5]Patent: WO2014/28931,2014,A2 .Location in patent: Page/Page column 132
[6]Journal of Physical Chemistry,1993,vol. 97,p. 13273 - 13283

9
[ 6136-68-1 ]
[ 4637-24-5 ]
[ 179055-13-1 ]

Yield	Reaction Conditions	Operation in experiment
79%	In N,N-dimethyl-formamide at 90℃;
79%	at 90℃; for 2h;
56.5%	at 110℃; for 1h;

	at 110℃; for 16h;	Step 1 : Preparation of (E)-3-(3-(Dimethylamino)acryloyl)benzonitrile A mixture of 3-acetylbenzonitrile (1 .50 g, 10 mmol) in N,N-dimethylformamide dimethyl acetal (10 mL) was stirred at 110°C for 16 hours. The product was indicated present via UPLC analysis. The mixture concentrated under reduced pressure. Crude product (E)-3-(3-(Dimethylamino)acryloyl)benzonitrile (2.00 g, 10 mmol, 100 %) was afforded as light yellow oil and was used directly in the next step without further purification. NMR data unavailable; LCMS (ESI) m/z: 201 [M+H]+.
	at 110℃; for 16h;	Step 1 : Preparation of (E)-3-(3-(Dimethylamino)acryloyl)benzonitrile A mixture of 3-acetylbenzonitrile (1 .50 g, 10 mmol) in N,N-dimethylformamide dimethyl acetal (10 mL) was stirred at 110°C for 16 hours. The product was indicated present via UPLC analysis. The mixture concentrated under reduced pressure. Crude product (E)-3-(3-(Dimethylamino)acryloyl)benzonitrile (2.00 g, 10 mmol, 100 %) was afforded as light yellow oil and was used directly in the next step without further purification. NMR data unavailable; LCMS (ESI) m/z: 201 [M+H]+.
	at 110℃; for 16h;	Step 1 : Preparation of (E)-3-(3-(Dimethylamino)acryloyl)benzonitrile A mixture of 3-acetylbenzonitrile (1 .50 g, 10 mmol) in N,N-dimethylformamide dimethyl acetal (10 mL) was stirred at 110°C for 16 hours. The product was indicated present via UPLC analysis. The mixture concentrated under reduced pressure. Crude product (E)-3-(3-(Dimethylamino)acryloyl)benzonitrile (2.00 g, 10 mmol, 100 %) was afforded as light yellow oil and was used directly in the next step without further purification. NMR data unavailable; LCMS (ESI) m/z: 201 [M+H]+.

Reference： [1]Tanaka, Akira; Terasawa, Takeshi; Hagihara, Hiroyuki; Kinoshita, Takayoshi; Sakuma, Yuri; Ishibe, Noriko; Sawada, Masae; Takasugi, Hisashi; Tanaka, Hirokazu [Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 1, p. 81 - 86]
[2]Tanaka, Akira; Terasawa, Takeshi; Hagihara, Hiroyuki; Sakuma, Yuri; Ishibe, Noriko; Sawada, Masae; Takasugi, Hisashi; Tanaka, Hirokazu [Journal of Medicinal Chemistry, 1998, vol. 41, # 13, p. 2390 - 2410]
[3]Stanek; Caravatti; Capraro; Furet; Mett; Schneider; Regenass [Journal of Medicinal Chemistry, 1993, vol. 36, # 1, p. 46 - 54]
[4]Current Patent Assignee: YUMANITY THERAPEUTICS INC - WO2021/247841, 2021, A1 Location in patent: Page/Page column 57-58
[5]Current Patent Assignee: YUMANITY THERAPEUTICS INC - WO2021/247841, 2021, A1 Location in patent: Page/Page column 57-58
[6]Current Patent Assignee: YUMANITY THERAPEUTICS INC - WO2021/247841, 2021, A1 Location in patent: Page/Page column 57-58

10
[ 6136-68-1 ]
[ 555-16-8 ]
3-[3-(4-nitrophenyl)-1-oxo-2-propenyl]benzonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.7 gm (97%)	With sodium methylate; In methanol;	Part A. Sodium methoxide (25% in MeOH, 1.5 mL, 6.8 mmol) was added dropwise to a solution of 3-acetylbenzonitrile (987 gm, 6.8 mmol) and 4-nitrobenzaldehyde (1 gm, 6.8 mmol) in dry methanol. Within 5 minutes, a precipitate begins to appear. The mixture was stirred at room temperature for 4 hours and diluted with methanol. The solids were filtered off, washed with cold methanol and dried to give 3-[3-(4-nitrophenyl)-1-oxo-2-propenyl]benzonitrile as a white solid 1.7 gm (97%) MS: 279(M+H)+; 1 H NMR (CDCl3): 7.60 (d, 1H), 7.70 (t, 1H), 7.85 (m, 4H), 8.25 (m, 4H)
1.7 gm (97%)	With sodium methylate; In methanol;	Part A. Sodium methoxide (25% in MeOH, 1.5 mL, 6.8 mmol) was added dropwise to a solution of 3-acetylbenzonitrile (987 gm, 6.8 mmol) and 4-nitrobenzaldehyde (1 gm, 6.8 mmol) in dry methanol. Within 5 minutes, a precipitate begins to appear. The mixture was stirred at room temperature for 4 hours and diluted with methanol. The solids were filtered off, washed with cold methanol and dried to give 3-[3-(4-nitrophenyl)-1-oxo-2-propenyl]benzonitrile as a white solid 1.7 gm (97%) MS: 279(M+H)+; 1H NMR (CDCl3): 7.60 (d, 1H), 7.70 (t, 1H), 7.85 (m, 4H), 8.25 (m, 4H).

Reference： [1]Journal of Medicinal Chemistry,1998,vol. 41,p. 53 - 62
[2]Patent: US5942544,1999,A
[3]Patent: EP892780,2002,B1

11
[ 6136-68-1 ]
[ 105-07-7 ]
3-[3-(4-cyanophenyl)-1-oxo-2-propenyl]benzonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.7 gm (97%)	With sodium methylate; In methanol;	Part A. Sodium methoxide (25% in MeOH, 1.5 mL, 6.8 mmol) was added dropwise to a solution of 3-acetylbenzonitrile (0.987 gm, 6.8 mmol) and 4-cyanobenzaldehyde (0.891 gm, 6.8 mmol) in dry methanol. Within 5 minutes, a precipitate began to form. The mixture was stirred at room temperature for 4 hrs and diluted with methanol. The solids were filtered off, washed with cold methanol and dried to give 3-[3-(4-cyanophenyl)-1-oxo-2-propenyl]benzonitrile as a white solid 1.7 gm (97%). MS: (M+H)+ 259; 1 H NMR (CDCl3): 7.55 (d, 1H), 7.65 (t, 1H), 7.75 (s, 4H), 7.85 (m, 2H), 8.25 (d, 1H), 8.30 (s, 1H).
1.7 gm (97%)	With sodium methylate; In methanol;	Part A. Sodium methoxide (25% in MeOH, 1.5 mL, 6.8 mmol) was added dropwise to a solution of 3-acetylbenzonitrile (0.987 gm, 6.8 mmol) and 4-cyanobenzaldehyde (0.891 gm, 6.8 mmol) in dry methanol. Within 5 minutes, a precipitate began to form. The mixture was stirred at room temperature for 4 hrs and diluted with methanol. The solids were filtered off, washed with cold methanol and dried to give 3-[3-(4-cyanophenyl)-1-oxo-2-propenyl]benzonitrile as a white solid 1.7 gm (97%). MS:(M+H)+ 259; 1H NMR (CDCl3): 7.55 (d, 1H), 7.65 (t, 1H), 7.75 (s, 4H), 7.85 (m, 2H), 8.25 (d, 1H), 8.30 (s, 1H).

Reference： [1]Journal of Medicinal Chemistry,1998,vol. 41,p. 53 - 62
[2]Patent: US5942544,1999,A
[3]Patent: EP892780,2002,B1

12
[ 6136-68-1 ]
[ 50916-55-7 ]
3-(2,2-dibromoacetyl)benzonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1: 8% 2: 78%	With bromine In chloroform at 20℃; for 2h;
1: 13% 2: 37%	With bromine In chloroform at 0℃; for 2h;

Reference： [1]Watson, Corrine Y.; Whish, William J. D.; Threadgill, Michael D. [Bioorganic and Medicinal Chemistry, 1998, vol. 6, # 6, p. 721 - 734]
[2]Location in patent: experimental part Perez, Daniel I.; Palomo, Valle; Pérez, Concepción; Gil, Carmen; Dans, Pablo D.; Luque, F. Javier; Conde, Santiago; Martínez, Ana [Journal of Medicinal Chemistry, 2011, vol. 54, # 12, p. 4042 - 4056]

13
[ 6136-68-1 ]
[ 83112-50-9 ]

Yield	Reaction Conditions	Operation in experiment
33%	With [bis(acetoxy)iodo]benzene; water; trifluoroacetic acid; In acetonitrile; at 80℃; for 10h;	To a mixture of 3-acetylbezonitrile (3.00 g, 20.4 mmol) and [bis(trifluoroacetoxy)iodo]benzene (17.6 g, 40.9 mmol) in acetonitrile/H2O (5:1, 144 ml), trifluoroacetic acid (3.15 ml, 40.9 mmol) was added and stirred at 80 C for 10 hours. The solvent was evaporated under reduced pressure and the residue was diluted with ethyl acetate (120 ml), washed with saturated aqueous NaHCCbeta solution (30 ml), dried (MgSO4 and K2CO3) and evaporated under reduced pressure. The residue was purified by column chromatography on silica (ethyl acetate/hexane, 45/55-65/35) to give 3-(2-hydroxyacetyl)benzonitrile (1.09 g, 33 %, yellow solid).

Reference： [1]Patent: WO2008/8398,2008,A2 .Location in patent: Page/Page column 359
[2]Bioorganic and Medicinal Chemistry,1998,vol. 6,p. 721 - 734

14
[ 6136-68-1 ]
[ 78950-32-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry,1998,vol. 6,p. 721 - 734
[2]Chemistry - A European Journal,2009,vol. 15,p. 8695 - 8697
[3]Catalysis science and technology,2015,vol. 5,p. 2865 - 2868
[4]Bioorganic and Medicinal Chemistry,2008,vol. 16,p. 3091 - 3107

15
[ 50916-55-7 ]
[ 6136-68-1 ]
[ 83112-49-6 ]
3-(2,2-Diethoxy-acetyl)-benzonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1: 64% 2: 3% 3: 32%	With potassium acetate; sodium iodide In ethanol for 6h; Heating;

Reference： [1]Watson, Corrine Y.; Whish, William J. D.; Threadgill, Michael D. [Bioorganic and Medicinal Chemistry, 1998, vol. 6, # 6, p. 721 - 734]

16
[ 6136-68-1 ]
[ 258525-51-8 ]

Yield	Reaction Conditions	Operation in experiment
83%	With borane-THF; (S)-1-methyl-3,3-diphenyl-hexahydropyrrolo[1,2-c][1,3,2]oxazaborole; In tetrahydrofuran; at -78 - 20℃; for 18.33h;	A solution of 3-acetylbenzonitrile (0.50 g, 3.4 mmol) in THF (10 mL) was added to a solution of 1M BH3-THF (2.1 mL, 2.1 mmol) and (S)-1-methyl-3,3- diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole (95 mg, 0.34 mmol) in THF (8 mL) at -78C dropwise over 20 min. The resulting solution was allowed to gradually warm to rt and stir for 18h. The reaction mixture was quenched with MeOH (0.2 mL), then water (1 mL). The mixture was stirred for 30 min, then diluted with EtOAc, washed with water and brine, then dried over Na2SO4, filtered and concentrated. The crude product was purified by flash chromatography to give 10A (420 mg, 83 %, 75.2% ee).1H NMR (500MHz, CDCl3) delta 7.70 (s, 1H), 7.62 (d, J=8.0 Hz, 1H), 7.57 (d, J=7.7 Hz, 1H), 7.49 - 7.44 (m, 1H), 4.96 (s, 1H), 1.92 (d, J=3.9 Hz, 1H), 1.52 (d, J=7.2 Hz, 2H).

Reference： [1]Patent: WO2018/5336,2018,A1 .Location in patent: Page/Page column 79-80
[2]Bioorganic and Medicinal Chemistry,1999,vol. 7,p. 2697 - 2704
[3]Organic and Biomolecular Chemistry,2016,vol. 14,p. 3404 - 3408

17
[ 6136-68-1 ]
[ 105-58-8 ]
[ 62088-13-5 ]

Yield	Reaction Conditions	Operation in experiment
		Step l :OSodium hydride (60% dispersion in oil, 8.27 g, 207 mmol, 3.00 equiv) was added to a solution of 3-acetylbenzonitrile (10.0 g, 68.9 mmol, 1 equiv) in tetrahydrofuran (300 mL). The reaction mixture was stirred at 60 C, and a solution of diethyl carbonate (12.5 mL, 103 mmol, 1.50 equiv) in tetrahydrofuran (60 mL) was added over 45 minutes. The light orange reaction mixture was stirred at 60 C for an additional 2 h, then was cooled to 22 C. Saturated aqueous ammonium chloride solution was added, and the mixture was concentrated to -1/2 volume by rotary evaporation. The resulting residue was partitioned between ethyl acetate and water. The organic layer was washed with saturated aqueous sodium chloride solution, and the washed solution was dried over sodium sulfate. The dried solution was filtered, and the filtrate was concentrated to afford ethyl 3-(3-cyanophenyl)-3-oxopropanoate (15 g, 100%) as a white solid. The crude reaction product was taken into the next step without further purification. Calcd(M+l)+: 218.1, Found: 218.0.
3.2 g (96%)	With hydrogenchloride; In tetrahydrofuran; mineral oil;	Part A. Preparation of ethyl 3-(3-cyanophenyl)-3-oxopropionate. To a suspension of sodium hydride (1.2 g of 60% suspension in mineral oil, hexane-washed, 30.3 mmol) in 40 mL of tetrahydrofuran was added diethyl carbonate (3.7 mL, 30.3 mmol) and 3-acetyl benzonitrile (2.2 g, 15.2 mmol). The resulting suspension was stirred at 65 C for 1 h and then was cooled to room temperature. There was added 40 mL of 10% aqueous HCl and the reaction mixture was diluted with ethyl acetate and the layers were separated. The organic layer was washed with brine, dried (MgSO4) and concentrated in vacuo to afford 3.2 g (96%) of the title compound, which was sufficiently pure to be used without purification. MS (NH3-CI) 218.3 (M+H)+.
3.2 g (96%)	With hydrogenchloride; In tetrahydrofuran; mineral oil;	Part A. Preparation of ethyl 3-(3-cyanophenyl)-3-oxopropionate. To a suspension of sodium hydride (1.2 g of 60% suspension in mineral oil, hexane-washed, 30.3 mmol) in 40 mL of tetrahydrofuran was added diethyl carbonate (3.7 mL, 30.3 mmol) and 3-acetyl benzonitrile (2.2 g, 15.2 mmol). The resulting suspension was stirred at 65 C. for 1 h and then was cooled to room temperature. There was added 40 mL of 10% aqueous HCl and the reaction mixture was diluted with ethyl acetate and the layers were separated. The organic layer was washed with brine, dried (MgSO4) and concentrated in vacuo to afford 3.2 g (96%) of the title compound, which was sufficiently pure to be used without purification. MS (NH3-CI) 218.3 (M+H)+.

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 1910 - 1915
[2]Bioorganic and Medicinal Chemistry Letters,2001,vol. 11,p. 641 - 645
[3]Patent: WO2011/46774,2011,A1 .Location in patent: Page/Page column 16
[4]Patent: EP946528,2003,B1
[5]Patent: US6187797,2001,B1

18
[ 6136-68-1 ]
[ 115098-69-6 ]

Yield	Reaction Conditions	Operation in experiment
91%	With methanol; sodium tetrahydroborate; at 20℃; for 6h;	To a stirred solution of 3-acetylbenzonitrile (2.0 g, 13.7 mmol) in methanol (30 mL), sodium borohydride (0.62 g, 15.5 mmol) was added and stirred at room temperature for 6 h. The reaction mixture was diluted with water (20 mL) and extracted with EtOAc (3 x 30 mL). The organic layer was dried and concentrated. The resulting crude was purified by flash chromatography (silica gel, 4g cartridge) using 20% EtOAc in hexanes to obtain 3-(l-hydroxyethyl)benzonitrile (Yield: 1.8 mg, 91%) as colourless liquid. LCMS (ES) m/z = 146.05 [M-H]; NMR (400 MHz, DMSO-d6) d ppm: 1.32 (d, J = 6.4 Hz, 3H), 4.77 (m, 1H), 5.39 (d, J= 4.4 Hz, 1H), 7.53 (t, J= 7.6 Hz, 1H), 7.69 (d, J = 7.6 Hz, 2H), 7.76 (s, 1H).
69.4 - 93.7%	With methanol; sodium tetrahydroborate; at 20℃; for 18h;Product distribution / selectivity;	2-Acetylbenzonitrile (1.0 g, 6.89 mmol) was dissolved in anhydrous methanol (20 mL), treated with sodium borohydride (0.52 g, 13.8 mmol) and stirred at ambient temperature for 18 hours. A saturated solution of ammonium chloride was added and the mixture was extracted with ethyl acetate. The combined organics were washed with water and brine, dried over anhydrous sodium sulfate, evaporated and chromatographed using a gradient of 50 to 100% ethyl acetate in hexanes to provide 0.95 g (93.7%) of 3-(1-Hydroxy-ethyl)-benzonitrile. MS m/z/z 148 (M+W)+.; 3-(1-Hydroxy-ethyl)-benzonitrile<strong>[6136-68-1]3-Acetylbenzonitrile</strong> (12.5 g, 86.3 mmol) was dissolved in anhydrous methanol (100 mL) and treated with sodium borohydride (6.53 g, 172.6 mmol) and stirred at ambient temperature 18 hours. A saturated solution of ammonium chloride was added and the mixture was extracted with ethyl acetate. The combined organics were washed with water and brine, dried over anhydrous sodium sulfate, evaporated, and chromatographed using a gradient of 50 to 100% ethyl acetate in hexanes to provide 8.81 g (69.4%) of the title compound. MS m/z 148 (M+H)+.
	With methanol; sodium tetrahydroborate; at 20℃; for 0.333333h;	To a solution of 3-acetylbenzonitrile (1 equivalent) in methanol at room temperature was added sodium borohydride (approx. 1.67 equivalents), and the reaction was stirred for approximately 20 minutes. Aqueous work-up provided the title compound.

Reference： [1]Patent: WO2019/175897,2019,A1 .Location in patent: Paragraph 00098
[2]Journal of Organic Chemistry,2014,vol. 79,p. 9150 - 9160
[3]Patent: US2009/170886,2009,A1 .Location in patent: Page/Page column 18; 30
[4]European Journal of Organic Chemistry,2002,p. 3326 - 3335
[5]Patent: WO2010/141761,2010,A2 .Location in patent: Page/Page column 55
[6]Organic and Biomolecular Chemistry,2011,vol. 9,p. 5863 - 5870

19
[ 557-21-1 ]
[ 2142-63-4 ]
[ 6136-68-1 ]

Reference： [1]Tetrahedron Letters,2007,vol. 48,p. 2555 - 2557
[2]Synlett,2003,p. 2237 - 2239

20
[ 3012-37-1 ]
3-acetylphenylboronic acid [ No CAS ]
[ 6136-68-1 ]

Reference： [1]Organic Letters,2006,vol. 8,p. 4331 - 4333

21
[ 21962-45-8 ]
[ 6136-68-1 ]
3-(4-cyano-2-methoxyphenyl)-1-(3-cyanophenyl)-2-propen-1-one [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 2468 - 2485

22
[ 6136-68-1 ]
[ 127852-31-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry,1999,vol. 7,p. 2697 - 2704
[2]Journal of the American Chemical Society,1990,vol. 112,p. 5741 - 5747
[3]Chemical Communications,2013,vol. 49,p. 8629 - 8631

23
[ 6136-68-1 ]
[ 179056-81-6 ]

Reference： [1]Journal of Medicinal Chemistry,1998,vol. 41,p. 2390 - 2410

24
[ 6136-68-1 ]
[ 179056-79-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 79 percent / 2 h / 90 °C 2: 61 percent / AcOH / 3.5 h / Ambient temperature 3: 84 percent / DIBAL / CH₂Cl₂; toluene / 0.5 h / -60 °C

Reference： [1]Tanaka, Akira; Terasawa, Takeshi; Hagihara, Hiroyuki; Sakuma, Yuri; Ishibe, Noriko; Sawada, Masae; Takasugi, Hisashi; Tanaka, Hirokazu [Journal of Medicinal Chemistry, 1998, vol. 41, # 13, p. 2390 - 2410]

25
[ 6136-68-1 ]
[ 21860-07-1 ]

Reference： [1]Chemische Berichte,1900,vol. 33,p. 3409

26
[ 24424-99-5 ]
[ 6136-68-1 ]
[ 165949-84-8 ]

Reference： [1]Patent: EP1184370,2002,A2 .Location in patent: Example 7

27
[ 6136-68-1 ]
[ 7726-95-6 ]
[ 50916-55-7 ]

Yield	Reaction Conditions	Operation in experiment
	In acetic acid	Preparation of 3- [2- (3-CYANOPHENYL)-2-OXOETHYLSULFANYL] BENZOIC acid (VIB 216) 3-acetylbezonitrile (2.5 g, 0.017 mole) was dissolved in acetic acid (50 ml) then bromine liquid (3 gm, 0.0187 mole) in acetic acid (12.5 ml) was added dropwise over 2 hrs. The reaction mixture was stirred overnight. The acetic acid was evaporated to yield a fawn coloured solid (3.63 gm). This was used in the next step without further purification.

Reference： [1]Current Patent Assignee: THE BURNET INSTITUTE - WO2004/58747, 2004, A1 Location in patent: Page 44-45

28
[ 6136-68-1 ]
[ 52334-81-3 ]
[ 372122-73-1 ]

Yield	Reaction Conditions	Operation in experiment
82%		[0147] A reaction vessel was charged with sodium hydride (as a 60% oil dispersion, 5.46 g, 136 mmol), DME (20 ml) and 2-chloro-5-trifluoromethylpyridine (7.9 g, 43.5 mmol). <strong>[6136-68-1]3-Acetylbenzonitrile</strong> (6 g, 41 mmol) in DME (60 ml) was added in portions to the mixture under nitrogen at 0 C. The mixture was allowed to warm to ambient temperature and then heated at 40-45 C. overnight. Upon completion of the reaction, the mixture was cooled to 5 C. and water was slowly and carefully added to the reaction mixture. The mixture was partitioned between ethyl acetate and water. The layers were separated, the organic layer washed with water and brine then dried over magnesium sulfate and concentrated to dryness. Trituration with cyclohexane and filtration afforded 9.8g (82%) of the title compound. [0148] Mass Spectrum: Found: (M-H) 289 [0149] HPLC (?=220-230 nm) RT 3.9 min

Reference： [1]Patent: US2003/212275,2003,A1 .Location in patent: Page/Page column 8

29
pyridinium tribromide [ No CAS ]
[ 6136-68-1 ]
[ 50916-55-7 ]

Yield	Reaction Conditions	Operation in experiment
58%	With sodium sulfite; In hexane; acetic acid; ethyl acetate;	Part A. 3-(2-bromoacetyl) benzonitrile To a solution of 3-acetobenzonitrile (5 g, 0.0344 mol) in 45 ml glacial acetic acid was added pyridinium tribromide (11.3 g, 0.0355 mol). Reaction was stirred at room temperature under argon overnight. Reaction was then quenched with a saturated sodium sulfite solution (20 ml) and extracted with 325 ml dichloromethane. Combined organic phases were washed with 225 ml water, dried over magnesium sulfate, filtered and concentrated in vacuo. Crude oil was chromatographed on silica gel using 5% EtOAc in hexane as the eluent to give 3-(2-bromoacetyl) benzonitrile (4.5 g, 58%) as a white solid. H1NMR (CDCl3) 4.371-4.403 (s, 2H); 7.613-7.664 (m, H); 7.838-7.888 (m, H); 8.192-8.261 (m, 2H)

Reference： [1]Patent: US6399627,2002,B1

30
N,N'-Dibromobarbituric acid [ No CAS ]
[ 6136-68-1 ]
[ 50916-55-7 ]

Yield	Reaction Conditions	Operation in experiment
1.28 g (81%)	In diethyl ether	EXAMPLE 105 STR56 3-(2-bromoacetyl)benzonitrile EXAMPLE 105 STR56 3-(2-bromoacetyl)benzonitrile To a solution of 1.02 g (7.04 mmol) of 3-acetylbenzonitrile in 70 mL of ethylether was added 1.02 g (3.52 mmol, 0.5 equiv) of dibromobarbituric acid. The mixture was allowed to stir at room temperature overnight. The resultant white slurry was filtered and the filtrate was concentrated. Purification by flash chromotography (silica gel, 20% ethyl acetate/hexane) gave 1.28 g (81%) of the title compound as a whim solid: 1 H NMR (400 MHz, CDCl3) δ8.26 (t, 1H, J=1.4 Hz), 8.20 (td, 1H, J=1.5, 8.0 Hz), 7.87 (dd, 1H, J=1.3, 7.8 Hz), 7.64 (t, 1H, J=7.9 Hz), 4.40 (s, 2H).
1.28 g (81%)	In diethyl ether	31 EXAMPLE 105 STR61 3-(2-bromoacetyl)benzonitrile EXAMPLE 105 STR61 3-(2-bromoacetyl)benzonitrile To a solution of 1.02 g (7.04 mmol) of 3-acetylbenzonitrile in mL of ethyl ether was added 1.02 g (3.52 mmol, 0.5 equiv) of dibromobarbituric acid. The mixture was allowed to stir at room temperature overnight. The resultant white slurry was filtered and the tiltrate was concentrated. Purification by flash chromotography (silica gel, ethyl acetate/hexane) gave 1.28 g (81%) of the title compound as a white solid: 1H NMR (400 MHz, CDCl3) δ 8.26 (t, 1H, J=1.4 Hz), 8.20 (td, 1H, J=1.5, 8.0 Hz), 7.87 (dd, 1H, J=1.3, 7.8 Hz), 7.64 (t, 1H, J=7.9 Hz), 4.40 (s, 2H).

Reference： [1]Current Patent Assignee: MERCK & CO INC - US5541197, 1996, A
[2]Current Patent Assignee: MERCK & CO INC - US5561142, 1996, A

31
[ 6136-68-1 ]
[ 53097-35-1 ]

Yield	Reaction Conditions	Operation in experiment
86%		Example 2.34: (3-isopropylphenyl)methanamine; [0274] To the methyl triphenylphosphoniumbromide (4.3 gm, 12 mmol) in THF at O0C, n- BuLi (1.6M, 7.5 ml, 12 mmol) was added and stirred for 30 min. Then 3-acetylbenzonitrile in THF was slowly added and the reaction mixture was stirred at O0C for further 3h. Then reaction mixture was quenched with aqeous ammonium chloride and diluted with ethyl acetate. Organic layer was washed with water, brine and dried. Crude residue after column purification yielded 3-(prop-l-en-2-yl)benzonitrile in 86% yield.

Reference： [1]Patent: WO2006/110668,2006,A1 .Location in patent: Page/Page column 64

32
[ 405548-42-7 ]
[ 6136-68-1 ]
[ 25895-60-7 ]
[ 144-55-8 ]
N-[1-(3-Cyanophenyl)ethyl]-N-(1-isobutyl-3-methyl-1H-pyrazol-4-yl)-2-acetoxyacetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With p-toluenesulfonic acid monohydrate; acetic acid In 5,5-dimethyl-1,3-cyclohexadiene; ethanol; hexane; ethyl acetate	5.1 N-[1-(3-Cyanophenyl)ethyl]-N-(1-isobutyl-3-methyl-1H-pyrazol-4-yl)-2-acetoxyacetamide (Exemplification compound number C-645) (1) 3-[1-(1-Isobutyl-5-methyl-1H-pyrazol-4-ylamino)ethyl]benzonitrile (Steps B1 and B2) To a solution of 4-amino-1-isobutylpyrazole (506.3 mg, 3.304 mmol) and 3-cyanoacetophenone (503.6 mg, 3.469 mmol) in xylene (35 ml) was added p-toluenesulfonic acid monohydrate (62 mg, 0.326 mmol), and the resulting mixture was refluxed for 1 hr. After cooling to room temperature, saturated aqueous sodium hydrogen carbonate solution was added to the reaction mixture, and the resulting mixture was extracted with ethyl acetate and dried over anhydrous magnesium sulfate. After removal of the drying agent by filtration, the filtrate was concentrated in vacuo, and the residue obtained was purified by chromatography on a silica gel column (eluent: from hexane to ethyl acetate/hexane (4/1)) to afford the imine derivative. To a solution of the obtained imine derivative in ethanol (20 ml) were added acetic acid (1.90 ml, 33.191 mmol) and 95% sodium cyanotrihydroborate (645.0 mg, 9.751 mmol) successively at 0ØC with stirring, and the resulting mixture was stirred at room temperature for 1 hr. After stirring, the reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution, extracted with ethyl acetate and dried over anhydrous magnesium sulfate. After removal of the drying agent by filtration, the filtrate was concentrated in vacuo, and the residue obtained was purified by chromatography on a silica gel column (eluent: from hexane to ethyl acetate/hexane (1/11)) to afford the title compound (588.0 mg, 2.082 mmol) in 63% yield. 1H-NMR (270 MHz, CDCl3) δ (ppm): 0.83(3H, d, J=7.0Hz), 0.85(3H, d, J=7.0Hz), 1.45(3H, d, J=6.4Hz), 2.07(3H, s), 2.09(1H, m), 3.72(2H, d, J=7.5Hz), 4.22(1H, q, J=6.5Hz), 6.91(1H, s), 7.35-7.72(4H,m). MASS (EI) m/z: 282(M+), 267, 152, 130, 103, 96, 57.

Reference： [1]Current Patent Assignee: MITSUI CHEMICALS,INC. - EP1329160, 2003, A2

33
[ 6136-68-1 ]
[ 105-56-6 ]
ethyl 2-amino-4-(3-cyanophenyl)thiophene-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%		General procedure: To a solution of arylacetophenone (30 mmol) in benzene or toluene (10 mL) was added ethylcyanoacetate or malononitrile (66 mmol), ammonium acetate (15 mmol) and acetic acid (60 mmol) and the reaction mixture was refluxed for 18 - 48h using a Dean Stark apparatus. After completion of reaction, the reaction mixture was cooled to room temperature, quenched with water (200 ml) and extracted with ethyl acetate (100ml x 2). The organic phase was dried over sodium sulphate, concentrated under reduced pressure and the residue was dissolved in ethanol (120 mL). Sulphur powder (40 mmol) and diethylamine (26 mmol) were added to the solution, which was heated at 50C for 3h. The hot solution was then filtered to remove unreacted sulphur. The resulting filtrate was concentrated to give crude product, which was purified by flash chromatography to afford the corresponding alkyl 2-amino-4-arylthiophene-3-carboxylate or 3-cyano-2-amino-4-arylthiophene.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 3034 - 3038
[2]Synlett,2006,p. 2559 - 2564
[3]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 692 - 702

34
[ 4254-67-5 ]
[ 6136-68-1 ]
[ 1014980-79-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 1063 - 1066

35
[ 6136-68-1 ]
[ 51012-64-7 ]
[ 1014980-73-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 1063 - 1066

36
[ 459-31-4 ]
[ 6136-68-1 ]
[ 777952-97-3 ]

Yield	Reaction Conditions	Operation in experiment
27%		A solution of BuLi (119 mmol) in hexanes (1.6 M, 74.3 mL) was added dropwise over 15 min to a stirred solution OF IPR2NH (16.6 mL, 119 mmol) in THF (150 mL) at 0C under N2. After 20 min, the reaction was cooled to-78C and a solution of 3- cyanoacetophenone (17.2 ML, 119 mmol) in THF (50 mL) was added dropwise over 5 min and then the mixture was stirred for a further hour. Meanwhile, CDI (9.64 g, 59.4 mmol) was added to a stirred solution OF 3- (4- fluorophenyl) propionic acid (10.0 g, 59.4 mmol) in THF (100 ML) at RT under N2. This was then stirred at RT for 45 min and added by CANNULA into the above solution at -78C under N2. The resulting solution was stirred at-78C for 45 min, before warming to RT and stirring for a further hour. The mixture was diluted with EtOAc (200 mL) and washed with 1M citric acid solution (2 x 100 mL), NAHCO3 solution (2 x 100 ML) and brine (50ML), dried (MGS04) and concentrated under reduced pressure. The residue was purified by column chromatography on silica eluting with 25% EtOAc/iso-hexane to yield the dicarbonyl compound (4.75 g, 27 %). H NMR (CDC13, 360 MHz) B 8.12 (1H, s), 8.05 (1H, d, J= 8.0 Hz), 7. 78 (1H, d, J= 8.0 Hz), 7.57 (1H, t, J= 8.0 Hz), 7.20-7. 10 (2H, m), 7.04-6. 92 (2H, m), 6.10 (1H, s), 3.00 (2H, t, J= 8.6 Hz), 2.76 (2H, t, J= 8.6 Hz).

Reference： [1]Patent: WO2004/89911,2004,A1 .Location in patent: Page 25; 26

37
[ 75-15-0 ]
[ 6136-68-1 ]
[ 74-88-4 ]
[ 838871-76-4 ]

Yield	Reaction Conditions	Operation in experiment
98%		To a suspension of NaH (60% oil suspension, 2.76 g) in DMSO (25 ml) was added a solution of 3-acetylbenzonitrile (5.00 g) in DMSO (25 ml). CS2 (2.07 ml) was added dropwise with external water bath cooling, and the mixture was stirred for 45 min. Methyl iodide (4.29 ml) was added dropwise with external water bath cooling, and the mixture was stirred at room temperature overnight. The reaction mixture was poured into water (300 ml), stirred for 10 min, and the resulting precipitate was collected by filtration and dried in vacuo to give 3-[3,3-bis(methylthio)acryloyl]benzonitrile (8.39 g, 98% yield) as a brown solid.1H NMR (500 MHz, DMSO-d6) delta 2.51 (s, 3H), 2.71 (s, 3H), 6.90 (s, 1H), 7.71 (t, J = 7.8 Hz, 1H), 8.03 (dt, J = 1.4, 7.8 Hz, 1H), 8.25 (dt, J = 1.4, 7.8 Hz, 1H), 8.44 (t, J= 1.4 Hz, 1H).

Reference： [1]Patent: EP1505064,2005,A1 .Location in patent: Page 19

38
[ 6136-68-1 ]
[ 106-95-6 ]
3-(2-hydroxypent-4-en-2-yl)benzonitrile [ No CAS ]

Reference： [1]Advanced Synthesis and Catalysis,2009,vol. 351,p. 3089 - 3095

39
potassiumhexacyanoferrate(II) trihydrate [ No CAS ]
[ 2142-63-4 ]
[ 6136-68-1 ]

Yield	Reaction Conditions	Operation in experiment
68%	With [Pd{C6H4(CH2N(CH2Ph)2)}(mu-Br)]2; tetrabutylammomium bromide; potassium carbonate; In N,N-dimethyl-formamide; at 130℃; for 0.166667h;Microwave irradiation;	General procedure: A mixture of the aryl halide (1 mmol), K4[Fe(CN)6]·3 H2O (0.22 mmol, 92.9 mg), TBAB (1 mmol, 322.4 mg), palladacycle catalyst (0.5 mmol %, 4.7 mg), and K2CO3 (1 mmol, 138.2 mg) was added to DMF (3 mL) in a round-bottomed flask equipped with a condenser and placed into the Milestone microwave. Initially using a microwave power of 600 W the temperature was ramped from room temperature to 130 C, this taking approximately 1 min, and then held at this temperature until the reaction was completed. During this time, the power was modulated automatically to keep the reaction mixture at 130 C. The mixture was stirred continuously using an appropriate magnet during the reaction. After the reaction was completed, the mixture was cooled to room temperature and diluted with water (30 ml) and ethyl acetate (30 ml). The organic layer was dried over MgSO4, filtered, and the solvent was evaporated using rotary evaporator. The residue was purified by silica gel column chromatography or by recrystallization using ethanol and water. The products were characterized by comparing their mp, IR, 1H, 13C NMR spectra with those found in the literature. [19] and [20]

Reference： [1]Chemical Communications,2012,vol. 48,p. 2909 - 2911
[2]Tetrahedron Letters,2012,vol. 53,p. 526 - 529
[3]Applied Organometallic Chemistry,2010,vol. 24,p. 454 - 457

40
[ 50-00-0 ]
[ 6136-68-1 ]
[ 506-59-2 ]
[ 1197342-24-7 ]

Yield	Reaction Conditions	Operation in experiment
		3.1 9.2 mul of 37% aqueous hydrochloric acid are added to a suspension of 725 mg (5.00 mmol) of 3-acetylbenzonitrile, 195 mg of paraformaldehyde and 530 mg (6.50 mmol) of dimethylammonium chloride in 1 ml of ethanol. The reaction mixture is stirred at 80 C. for 18 hours. The reaction mixture, a solid mass, is cooled to room temperature taken up in acetone, filtered and washed with a little acetone. The residue is dissolved in water and extracted with dichloromethane. The aqueous phase is adjusted to a pH of 9 using 10 ml of 1 N NaOH and extracted with dichloromethane. The organic phase is dried over sodium sulfate and evaporated: 3-(3-dimethylaminopropionyl)benzonitrile as brown oil; ESI 203.
	With hydrogenchloride; In ethanol; water; at 90℃; for 18h;Sealed tube;	General procedure: A mixture of 1-(benzo[d][1,3]dioxol-4-yl)ethan-1-one(4.8 g, 29.3 mmol), dimethylamine HCl (3.08 g, 38 mmol) andparaformaldehyde (1.14 g, 38 mmol) in EtOH (100 mL) and HCl (0.8 mL) wasrefluxed in a sealed tube for 18 h. The solvent was evaporated and the solidresidue was partitioned between EtOAc and water. The aqueous portion wasbasified with 2M NaOH and then extracted with EtOAc (3 x 100 mL). The organicfractions were washed with water and brine, then dried over Na2SO4 andevaporated to give 1-(Benzo[d][1,3]dioxol-4-yl)-3-(dimethylamino)propan-1-one (55i) (1.80 g, 28%).

Reference： [1]Patent: US2011/71153,2011,A1 .Location in patent: Page/Page column 23
[2]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 5190 - 5196

41
[ 6136-68-1 ]
[ 196929-78-9 ]
[ 1286182-82-8 ]

Yield	Reaction Conditions	Operation in experiment
78%		<strong>[6136-68-1]3-Acetylbenzonitrile</strong> (5g, 34.4 mmol) is added to a flask containing (R)-(+)-2-Methyl-2- propanesulfmamide (3.48g, 28.7 mmol) and Titinium (IV) ethoxide (13.1 g, 57.4 mmol) in THF (70 mL) and the reaction mixture heated at 75C overnight. The reaction mixture is cooled (-48C) and L-Selectride (1M solution in THF, 57.4 mL) added dropwise over lhour. The reaction stirred for 2hrs and allowed to warm to room temperature. The reaction is then cooled to 0C and methanol (3 mL) added. Brine (150 mL) is added with stirring and the suspension filtered through celite. The crude material is extracted with ethyl acetate, dried (MgS04), filtered and evaporated under vacuum. The cruse is purified by column chromatography eluting with heptane-ethyl acetate to give N- \|Y 1 S)- 1 -(3 -cyanophenyDethyl] - 2 -methyl- \|"S(R)]- 2-propanesulfmamide (78 %)MS: 251 (M+H)lB NMR (300 MHz, CDC13): delta = 1.22 (s, 9H), 1.54 (d, 3H), 3.36 (bs, 1H), 4.55-4.7 (m, 1H), 7.43 (d, 1H), 7.46 (d, 1H), 7.56-7.6 (m, 2H), 7.64 (s, 1H).

Reference： [1]Patent: WO2011/44307,2011,A1 .Location in patent: Page/Page column 31

42
[ 75369-41-4 ]
[ 6136-68-1 ]
[ 1263183-73-8 ]
[ 41908-11-6 ]

Reference： [1]Australian Journal of Chemistry,2010,vol. 63,p. 1645 - 1655

43
[ 544467-05-2 ]
[ 6136-68-1 ]
[ 1263183-73-8 ]
[ 41908-11-6 ]

Reference： [1]Australian Journal of Chemistry,2010,vol. 63,p. 1645 - 1655

44
[ 585-74-0 ]
[ 6136-68-1 ]
[ 1263183-73-8 ]
[ 41908-11-6 ]

Reference： [1]Australian Journal of Chemistry,2010,vol. 63,p. 1645 - 1655

45
[ 6136-68-1 ]
[ 298-12-4 ]
[ 52240-08-1 ]

Yield	Reaction Conditions	Operation in experiment
		Examples of the Preparation of the Pyradizinone Starting Compounds The pyridazinones are generally prepared by processes from W. H. Coates, A. McKillop, Synthesis 1993, p. 334. An example thereof is the synthesis of 3-(6-oxo-1,6-dihydropyridazin-3-yl)benzonitrile: 927 g (10.6 mol) of glyoxylic acid monohydrate are introduced in portions into a solution of 1278 g (8.80 mol) of 3-acetylbenzonitrile in 1.5 l of acetic acid. The resultant solution is heated at 95 C. for 18 hours. The mixture is allowed to cool to 30 C., and 7 l of water and 899 ml (18.5 mol) of hydrazinium hydroxide are added successively. The reaction mixture is stirred at 95 C. for 4 hours. The mixture is allowed to cool to 60 C., and the resultant precipitate is filtered off with suction and washed with 5 l of water and 2 l of acetone. The residue is heated to the boil in 5 l of acetone and filtered off with suction while hot. 5 l of acetic acid are added to the residue, and the mixture is heated at 90 C. for 2 hours with stirring. The mixture is allowed to cool to room temperature, and the residue is filtered off with suction and washed with acetone. The residue is again heated to 90 C. with 5 l of acetic acid, cooled to room temperature, filtered off with suction and washed with acetone. The residue is dried in vacuo: 3-(6-oxo-1,6-dihydropyridazin-3-yl)benzonitrile as beige crystals; ESI 198. Some pyridazinones can be prepared in accordance with A. J. Good-man et al., Tetrahedron 55 (1999), 15067-15070. An example thereof is the alternative synthesis of 3-(6-oxo-1,6-dihydropyridazin-3-yl)benzo-nitrile:

Reference： [1]Patent: US2011/257181,2011,A1 .Location in patent: Page/Page column 20

46
[ 6136-68-1 ]
[ 95-92-1 ]
ethyl 4-(3-cyanophenyl)-2-hydroxy-4-oxobut-2-enoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%		General procedure: Following the reported procedure refPreviewPlaceHolder[25], sodium ethoxide (0.43 g, 6.30 mmol) was added into a well stirred mixture of appropriate acetyl derivatives (3.12 mmol) and diethyl oxalate (0.92 g, 6.24 mmol) in anhydrous THF (15 mL) under nitrogen atmosphere. The reaction mixture was stirred at room temperature and upon completion of the reaction, was poured into n-hexane (50 mL). The precipitates were collected and then vigorously stirred in 1N HCl (30 mL) for 30 min. The resultant solid formed was filtered, washed with water, and dried under vacuum. The crude mass obtained was further dissolved in ethyl acetate and reprecipitated with hexane to obtain desired esters 1-20 and 22-24.

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 5138 - 5145

47
[ 41908-11-6 ]
[ 6136-68-1 ]

Yield	Reaction Conditions	Operation in experiment
83%	With hydroxylamine hydrochloride; In glycerol; at 90℃; for 8h;Green chemistry;	General procedure: To a round bottom flask aldehydes (1a-1q) (1.0 mmol) and hydroxylamine hydrochloride (1.0 mmol) was added in glycerol (5 ml). The reaction mixture was allowed to stir at 90 C for the time indicated in Table 2. After the completion of reaction, the reaction mixture was washed with a mixture of hexane/Ethyl acetate (95:5) (3 * 3 mL) and the organic phase were separated from glycerol, dried with MgSO4, and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel using hexane/ethyl acetate as eluent. All the compounds were characterized by comparison with mp and 1H NMR, 13C NMR spectra with literature.

Reference： [1]Tetrahedron Letters,2017,vol. 58,p. 4845 - 4848
[2]Journal of Organic Chemistry,2012,vol. 77,p. 9334 - 9337,4

48
[ 16982-21-1 ]
[ 6136-68-1 ]
[ 1266520-53-9 ]

Yield	Reaction Conditions	Operation in experiment
65%		Example 34A Ethyl 4-(3-cyanophenyl)-1,3-thiazole-2-carboxylate At room temperature, 10 drops of a conc. aqueous hydrogen chloride solution are added to 5.00 g (34.4 mmol) of 3-acetylbenzenecarbonitrile in 40 ml of conc. acetic acid. 1.8 ml (34.4 mmol) of bromine in 10 ml of conc. acetic acid are subsequently added dropwise over a period of 1 h, and after the end of the addition, the reaction mixture is poured onto ice. After extraction of the aqueous phase with dichloromethane, the combined organic phases are dried over MgSO4, filtered and concentrated under reduced pressure. The solid obtained (8.00 g) is provided in 250 ml of EtOH and heated under reflux, a solution of 3.77 g (28.3 mmol) of ethyl amino(thioxo)acetate in 50 ml of ethanol is added dropwise and the mixture is stirred under reflux for 3 h. The reaction solution is cooled and the precipitate formed is collected by filtration. The mother liquor is concentrated under reduced pressure, the residue is taken up in a little ethanol and the solid formed is subsequently collected by filtration. 5.75 g (65% of theory) of the title compound are obtained after combining the solids. 1H-NMR (400 MHz, DMSO-d6): delta=8.74 (s, 1H), 8.45 (s, 1H), 8.35 (d, 1H), 7.88 (d, 1H), 7.77-7.62 (m, 1H), 4.43 (q, 2H), 1.37 (t, 3H). LC-MS (Method 5): Rt=1.15 min; MS (ESIpos): m/z=259 [M+H]+.

Reference： [1]Patent: US2013/45999,2013,A1 .Location in patent: Paragraph 0271; 0272; 0273; 0274

49
[ 6136-68-1 ]
[ 2065-66-9 ]
[ 53097-35-1 ]

Yield	Reaction Conditions	Operation in experiment
79%		A solution of n-BuLi (20.0 mL, 2.5 M, 50.0 mmol) was added to a solution of PPh3MeI (20.2 g, 50.0 mmol) in THF (200 mL) at -10 C. After the mixture was stirred at -10 C for 1 h, 3-acetylbenzonitrile (4.85 g, 33.4 mmol) was added. The mixture was allowed to warm up to r.t. and stirred at r.t. for 3 h. Water (400 mL) was added to the reaction mixture and it was extracted with CH2Cl2 (200 mL x 2). It was dried over anhydrous sodium sulfate, and purified by column chromatography (PE: EtOAc = 50: 1) to give the titled compound (3.4 g, 79%).

Reference： [1]Patent: WO2013/24011,2013,A1 .Location in patent: Page/Page column 64

50
[ 6136-68-1 ]
[ 616-38-6 ]
[ 209731-74-8 ]

Yield	Reaction Conditions	Operation in experiment
86%	With sodium hydride; In toluene; at 100℃; for 2h;Inert atmosphere; Reflux;	Example C7: Methyl 3- 3-cyanop eny -3-oxopropanoate: [0151] Into a three-necked flask equipped with an argon inlet and a condenser were placed sodium hydride (60%>, 689.5 mg, 17.23 mmol), dimethyl carbonate (1.55 g, 17.23 mmol) and 15 mL of toluene. The mixture was stirred under reflux and a solution of 3- acetylbenzonitrile (1.0 g, 6.19 mmol) in toluene (15 mL) was added drop wise. The reaction mixture was stirred at 100C for 2h. The reaction mixture was monitored by LCMS and purified by column chromatography on silica gel eluted with 0-10% of ethyl acetate in petroleum ether to give the product (1.2 g, 86%>).
67.8%	With sodium hydride; In mineral oil; at 0 - 60℃; for 7h;Inert atmosphere;	[00458] To a stirred solution of 3-acetylbenzonitrile (1 g, 6.89 mmol) in dry THF (30 mL) under inert atmosphere was added sodium hydride (60%>) (326 mg, 13.5 mmol) portion wise at 0C followed by dimethyl carbonate (1.24 g, 13.7 mmol). The reaction mixture was heated to 60 C and stirred for 7 h; progress of the reaction was monitored by TLC. The reaction mixture was quenched with dil. HC1 (2 mL), diluted with water (50 mL) and extracted with EtOAc (2 x 30 mL). The combined organic extracts were dried over anhydrous Na2SO4 and concentrated under reduced pressure to obtain the crude product. The crude material was purified by silica gel column chromatography eluting with 10% EtOAc/Hexane to afford compound H as a mixture of its enolic form (950 mg, 67.8%) as a pale yellow liquid. 1H NMR (500 MHz, DMSO-^): delta 8.40 (s, 1H), 8.31-8.22 (m, 1H), 8.19-8.12 (m, 1H), 7.77-7.75 (m, 1H), 4.29 (s, 2H), 3.64 (s, 3H). MS (ESI): m/z 204 [M+l] +.

Reference： [1]Patent: WO2013/33246,2013,A2 .Location in patent: Paragraph 0151
[2]Patent: WO2015/191630,2015,A1 .Location in patent: Paragraph 00458

51
[ 153994-67-3 ]
[ 6136-68-1 ]
[ 127852-31-7 ]

Reference： [1]Chemical Communications,2013,vol. 49,p. 8629 - 8631

52
[ 6136-68-1 ]
[ 122-51-0 ]
[ 1616491-13-4 ]

Yield	Reaction Conditions	Operation in experiment
90%	With toluene-4-sulfonic acid; In ethanol; at 20℃; for 4h;	A solution of 3-acetylbenzonitrile (725 mg, 5 mmol), p-toluenesulfonic acid (95 mg, 0.5 mmol) and triethoxy methane (1.67 mL, 10 mmol) in EtOH (15 mL) was stirred at rt for 4 h. Sodium ethoxide was added and the mixture was filtered through Celite pad and the organic layer was concentrated to give 986 mg (90%) of 12 as a colorless oil. 1H NMR (300 MHz, CDCl3) delta 7.86 (q, J = 1.7 Hz, 1H), 7.77-7.71 (m, 1H), 7.61-7.54 (m, 1H), 7.49-7.41 (m, 1H), 3.54-3.41 (m, 2H), 3.37-3.25 (m, 2H), 1.53 (s, 3H), 1.21 (td, J = 7.1, 1.5 Hz, 6H).

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 3670 - 3683

53
[ 6136-68-1 ]
[ 115262-01-6 ]
3-(2-fluoroacryloyl)benzonitrile [ No CAS ]

Reference： [1]Organic Letters,2015,vol. 17,p. 1712 - 1715

54
[ 6136-68-1 ]
[ 1489-69-6 ]
3-(3-cyclopropylacryloyl)benzonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydroxide; In methanol; water; at 0 - 20℃; for 14h;	To a stirred solution of 3-acetylbenzonitrile (2l4a) (50 g, 344 rnrnol) in methanol (800 mL) at 0 C was added cyclopropanecarboxaldehyde (41 rnL, 549 mmol) followed by potassium hydroxide (IM. aqueous solution, 67 niL, 67 mmol). The reaction mixtureallowed to attain room temperature and stirred for 14h. The reaction was acidified with HCI to pH-6 (75 mL, 1 N) and concentrated in vacuum maintaining bath temperature below 35C. The residue was diluted with ethyl acetate (1200 m.L) and washed with water (800 mL). The aqueous layer was extracted with ethyl acetate (800 rnL) and organic layers were combined washed with brine, dried, filtered and concentrated in vacuum to afford 3-(3-cyclopropylacryloyl)benzonitrile (214b) (72.42 grn) crude as a colorless liquid, which was used as such in next step; ?K NMR (300 MHz, DMSO-d6) 8.19 (dp, J= 7.8, 1.6 Hz, I H), 8.11 (dddt, J 6.3, 3.7, 2.6, 1.4 Hz, IH), 7.80 - 7.65 (m, 2H), 7.32 (dd, .1 15.1, 7.6 Hz, IH),6.60(ddd,J= 15.0,11.3,10.4Hz, 1K), 1.91- 1.74(m, 111), l.04(.m,2H),0.85-0.75 (m, 2H).
	With potassium hydroxide; In methanol; water; at 0 - 20℃; for 14h;	Step: 1 Preparation of 3-(3-cyclopropylacryloyl)benzonitrile (4b) To a stirred solution of 3-acetylbenzonitrile (4a) (50 g, 344 mmol) in methanol (800 mL) at 0 C was added cyclopropanecarboxaldehyde (41 mL, 549 mmol) followed by potassium hydroxide (1M aqueous solution, 67 mL, 67 mmol). The reaction mixture allowed to attain room temperature and stirred for 14h. The reaction was acidified with HCl to pH-6 (75 mL, 1 N) and concentrated in vacuum maintaining bath temperature below 35 C. The residue was diluted with ethyl acetate (1200 mL) and washed with water (800 mL). The aqueous layer was extracted with ethyl acetate (800 mL) and organic layers were combined washed with brine, dried, filtered and concentrated in vacuum to afford 3-(3- cyclopropylacryloyl)benzonitrile (4b) (72.42 gm) crude as a colorless liquid, which was used as such in next step; 1H NMR (300 MHz, DMSO-i) delta 8.19 (dp, J= 7.8, 1.6 Hz, 1H), 8.11 (dddt, J= 6.3, 3.7, 2.6, 1.4 Hz, 1H), 7.80 - 7.65 (m, 2H), 7.32 (dd, J= 15.1, 7.6 Hz, 1H), 6.60 (ddd, J= 15.0, 11.3, 10.4 Hz, 1H), 1.91 - 1.74 (m, 1H), 1.04 (m, 2H), 0.85 - 0.75 (m, 2H).

Reference： [1]Patent: WO2015/134998,2015,A1 .Location in patent: Page/Page column 701; 702
[2]Patent: WO2017/59178,2017,A1 .Location in patent: Page/Page column 53-54

55
[ 139697-98-6 ]
[ 6136-68-1 ]

Reference： [1]Organic Letters,2016,vol. 18,p. 860 - 863

56
[ 6136-68-1 ]
4-(4-chlorophenyl)cyclohexanecarbohydrazide [ No CAS ]
(E)-4-(4-chlorophenyl)-N'-(1-(3-cyanophenyl)ethylidene)cyclohexanecarbohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	In ethanol; for 3h;Reflux; Inert atmosphere;	General procedure: To a stirred solution of compound 3 (100 mg, 0.40 mmol) in ethanol was added corresponding acetophenones a-k (1.0 mmol) and refluxed for 3 h. The reaction medium was poured into water and extracted with ethyl acetate. The organic layer was washed with water followed by brine solution, dried over anhyd. Na2SO4, filtered and concentrated under reduced pressure, to obtain the pure compounds. Yields of the products varied between 80 and 94%.

Reference： [1]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,2016,vol. 55B,p. 718 - 723

57
[ 6136-68-1 ]
1-(3-(1H-tetrazole-5-yl)phenyl)ethanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With sodium azide; triethylamine hydrochloride;	General procedure: A mixture of a benzonitrile, 3a (310mg, 3mmol), 28 sodium azide (586mg, 9 mmol), and 29 triethylamine hydrochloride (1.24 g, 9 mmol) in 30 toluene (80 mL) was heated to 100C for 24h with stirring. After cooling, the reaction mixture was extracted with water. Then, 36% 31 HCl was added dropwise to the aqueous layer. Precipitation occurred, which was filtered off and washed with water to provide 32 4a as white solid (395mg, 90%). Mp: 214-216C. 1H NMR (500MHz, DMSO-d6): delta 8.04-7.02 (m, 2H), 7.62-7.57 (m, 3H)

Reference： [1]Bioorganic and Medicinal Chemistry,2017,vol. 25,p. 5278 - 5289

58
[ 6136-68-1 ]
[ 58326-67-3 ]
methyl 3<SUP>2</SUP>-(3-cyanobenzoyl)pyropheophorbide-a [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
35%	With sodium methylate; In methanol; chloroform; for 0.5h;Cooling with ice; Inert atmosphere; Darkness;	General procedure: To a 1:1 chloroform and methanol solution (16ml) of aldehyde 1 (10.2 mg, 18.5 mumol) and p-nitroacetophenone (0.98 g, 5.9 mmol), was added 28% sodium methoxide in methanol (1 ml, 5 mmol). After being stirred in an ice bath for 30 min, the reaction mixture was washed with an aqueous 2% hydrochloric acid solution, an aqueous saturated sodium hydrogen carbonate solution and distilled water, and dried over sodium sulfate. The solvents were evaporated and the residue was purified with FCC (5-6% Et2O-CH2Cl2) and recrystallization (CH2Cl2-hexane) to give 2i (4.3 mg, 6.2 mumol, 33% isolated yield).

Reference： [1]Tetrahedron,2018,vol. 74,p. 2703 - 2715

59
[ 6136-68-1 ]
[ 95-92-1 ]
ethyl 4-(3-cyanophenyl)-2-hydroxy-4-oxobutanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76.7%		Potassium tert-butoxide (4.5 g, 40.10mmol) was taken in dry diethyl ether (200ml)at room temperature under N2 atmosphere at stirring condition. Diethyl oxalate (4.4 ml, 30.10mmol) was added to that solution. After 15 min of stirring, 3-acetylbenzonitrile (4.35 g, 29.96 mmol) was added to the resulting mixtureand the stirring was continuing for overnight.A light yellow precipitate was obtained and the whole resulting mixture is taken in a separating funnel. This solution was washed three times with 20 ml of water. The entire aqueous layer was collected in a beaker, cooled for some time and then dilute HCl (2 ml) was added to it dropwise until the whole solution became just acidic. A yellow precipitate was obtained which was filtered and product ethyl 4-(3-cyanophenyl)-2,4-dioxobutanoatewas isolated as a yellow solid (3.3 g, 76.74 yield).

Reference： [1]Polyhedron,2019,vol. 160,p. 46 - 52

60
[ 6136-68-1 ]
[ 95-92-1 ]
lithium (Z)-1-(3-cyanophenyl)-4-ethoxy-3,4-dioxo-but-1-en-1-olate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of 1M (THF) LHMDS (37.89 ml, 37.89 mmol) in THF (20 ml, 0.247 mol) was slowly addded a solution of 3-acetylbenzonitrile (5 g, 34.4 mmol) in diethyl ether (25 ml) and diethyl ether (60 ml, 0.57 mol) in order to solubilize the substrate stirring at -78C. After 45 mm at -78C diethyl oxalate (5.15m1, 37.89 mmol) was added dropwise and the reaction mixture was then stirred at room temperature for 1 6h. The reaction mixture was concentrated and the crude title product so obtained was used in the next step without further purification considering a quantitative yield.

Reference： [1]Patent: WO2019/2571,2019,A1 .Location in patent: Paragraph 00349

61
[ 100-69-6 ]
[ 6136-68-1 ]
(R)-3-(2-hydroxy-4-(pyridin-2-yl)butan-2-yl)benzonitrile [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2019,vol. 141,p. 5437 - 5443

62
[ 6136-68-1 ]
[ 50910-55-9 ]
3-((E)-3-(2-amino-3,5-dibromophenyl)acryloyl)benzonitrile [ No CAS ]

Reference： [1]Egyptian Journal of Chemistry,2019,vol. 62,p. 1441 - 1450

63
[ 941-69-5 ]
[ 6136-68-1 ]
3-(4,6-dioxo-5-phenyl-3a,5,6,6a-tetrahydro-4H-pyrrolo[3,4-d]isoxazole-3-carbonyl)benzonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With tert.-butylnitrite; In dimethyl sulfoxide; at 80℃; for 4h;Inert atmosphere;	General procedure: To a 10 mL Schlenk tube, ketone 1a (0.6mmol, 1.2 equiv), Maleimides 2a (0.5 mmol, 1equiv), and t-BuONO 1.2 mmol, 2.4 equiv) were dissolved in DMSO (2.0 mL). Then the mixture was stirred at 80 for 4 h. To the residue was added water (10 mL) and extracted with ethyl acetate (5 mL * 3). The combined organic fractions were dried over Na2SO4, and concentrated under vacuum to yield the crude product, which was purified by column chromatography to give 3a,6a-dihydro-4H-pyrrolo[3,4-d]isoxazole-4,6(5H)-dione derivatives.

Reference： [1]Tetrahedron Letters,2020,vol. 61

64
[ 6136-68-1 ]
[ 1774-47-6 ]
3-(2-methyloxetan-2-yl)benzonitrile [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2020,vol. 59,p. 7521 - 7527
Angew. Chem.,2020,vol. 132,p. 7591 - 7597,7

Same Skeleton Products

Related Products

Historical Records

Related Functional Groups of
[ 6136-68-1 ]

Aryls

[ 32446-66-5 ]

4,4'-Dicyanobenzophenone

Similarity: 0.95

[ 1503-49-7 ]

4-Benzoylbenzonitrile

Similarity: 0.95

[ 90401-84-6 ]

6-Cyano-1-tetralone

Similarity: 0.92

[ 25724-79-2 ]

2,3-Dihydro-1-oxo-1H-indene-5-carbonitrile

Similarity: 0.92

[ 69975-66-2 ]

3-Oxo-indan-5-carbonitrile

Similarity: 0.92

Ketones

[ 32446-66-5 ]

4,4'-Dicyanobenzophenone

Similarity: 0.95

[ 1503-49-7 ]

4-Benzoylbenzonitrile

Similarity: 0.95

[ 90401-84-6 ]

6-Cyano-1-tetralone

Similarity: 0.92

[ 25724-79-2 ]

2,3-Dihydro-1-oxo-1H-indene-5-carbonitrile

Similarity: 0.92

[ 69975-66-2 ]

3-Oxo-indan-5-carbonitrile

Similarity: 0.92

Nitriles

[ 32446-66-5 ]

4,4'-Dicyanobenzophenone

Similarity: 0.95

[ 1503-49-7 ]

4-Benzoylbenzonitrile

Similarity: 0.95

[ 90401-84-6 ]

6-Cyano-1-tetralone

Similarity: 0.92

[ 25724-79-2 ]

2,3-Dihydro-1-oxo-1H-indene-5-carbonitrile

Similarity: 0.92

[ 69975-66-2 ]

3-Oxo-indan-5-carbonitrile

Similarity: 0.92

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
{[ item.p_purity ]}	{[ item.pr_size ]}	{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]}	{[ getRatePrice(item.pr_usd, 1,1) ]}	Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]}	{[ item.pr_usastock ]}	Inquiry -	{[ item.pr_chinastock ]}	Inquiry -

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. 6136-68-1 ] {[proInfo.proName]}

Quality Control of [ 6136-68-1 ]

Related Doc. of [ 6136-68-1 ]

Product Details of [ 6136-68-1 ]

Calculated chemistry of [ 6136-68-1 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 6136-68-1 ]

Application In Synthesis of [ 6136-68-1 ]

[ 6136-68-1 ] Synthesis Path-Upstream 1~2

[ 6136-68-1 ] Synthesis Path-Downstream 1~64

Related Functional Groups of [ 6136-68-1 ]

Aryls

Ketones

Nitriles

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 6136-68-1 ]