[ CAS No. 500912-18-5 ]

Name: 500912-18-5|2-(2-Fluoro-6-methoxyphenyl)acetonitrile|95%
Brand: Ambeed
SKU: A260255
Price: 7.0 USD
Availability: InStock
Rating: 98 (25 reviews)

{[proInfo.proName]} ,{[proInfo.pro_purity]}

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

2D 3D

Structure of 500912-18-5 * Storage: {[proInfo.prStorage]}

Cart0 Add to My Favorites Bulk Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

For Research Only 100K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 500912-18-5 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 500912-18-5 ]

SDS Specification

Alternatived Products of [ 500912-18-5 ]

Product Details of [ 500912-18-5 ]

CAS No. :	500912-18-5	MDL No. :	MFCD00671772
Formula :	C₉H₈FNO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	IHTMDGUTWAQZBU-UHFFFAOYSA-N
M.W :	165.16 g/mol	Pubchem ID :	2779324
Synonyms :

Calculated chemistry of [ 500912-18-5 ]

Physicochemical Properties

Num. heavy atoms :	12
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.22
Num. rotatable bonds :	2
Num. H-bond acceptors :	3.0
Num. H-bond donors :	0.0
Molar Refractivity :	42.41
TPSA :	33.02 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) :	-6.14 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.98
Log Po/w (XLOGP3) :	1.65
Log Po/w (WLOGP) :	2.32
Log Po/w (MLOGP) :	1.86
Log Po/w (SILICOS-IT) :	2.55
Consensus Log Po/w :	2.07

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.14
Solubility :	1.19 mg/ml ; 0.00722 mol/l
Class :	Soluble
Log S (Ali) :	-1.96
Solubility :	1.82 mg/ml ; 0.011 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-3.29
Solubility :	0.0855 mg/ml ; 0.000518 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.5

Safety of [ 500912-18-5 ]

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 [ 500912-18-5 ]

* 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 [ 500912-18-5 ]
Downstream synthetic route of [ 500912-18-5 ]

[ 500912-18-5 ] Synthesis Path-Upstream 1~2

1
[ 773837-37-9 ]
[ 146137-74-8 ]
[ 500912-18-5 ]

Yield	Reaction Conditions	Operation in experiment
46%	at 80℃; for 4 h;	To a solution of Scheme 56 compound 3 (5.7 g, 26.15 mmol) in dry EtOH (70 mL) was added NaCN (1.4 g, 28.76 mmol) and the reaction mixture was stirred at 80 °C for 4 h. After TLC showed the starting material was completely consumed, the reaction mixture was concentrated to give a crude compound which was diluted with ice water (30 mL) and extracted with EtOAc (2 x 50 mL). The organic layer was washed with brine (20 mL), dried over Na₂S0₄ and concentrated to give a residue which was purified by column chromatography (eluting with petroleum ether/EtOAc 100/0 gradually increasing to 60/40) to give Scheme 56 compound 4 (2.0 g, 46percent) as a colorless liquid. MS [ESI, MH⁺] = 166.06.

Reference： [1] Patent: WO2014/52365, 2014, A1, . Location in patent: Page/Page column 299-300

2
[ 137654-21-8 ]
[ 500912-18-5 ]

Reference： [1] Patent: WO2014/52365, 2014, A1,

[ 500912-18-5 ] Synthesis Path-Downstream 1~34

1
[ 959163-01-0 ]
[ 500912-18-5 ]
[ 1588424-20-7 ]

Yield	Reaction Conditions	Operation in experiment
61%	With potassium carbonate; In N,N-dimethyl-formamide; at 100℃; for 16h;Inert atmosphere;	A mixture of 6-chloro-4-(ethyl amino) nicotinaldehyde (Scheme 1 compound 6) (1.7 g, 9.32 mmol), Scheme 56 compound 4 (2.0 g, 12.11 mmol) and K2C03 (3.8 g, 27.96 mmol) in dry DMF (10 mL) was heated to 100 C under nitrogen atmosphere for 16 h. After TLC showed the starting material was completely consumed, the reaction mixture was cooled to RT, diluted with EtOAc (2 x 50 mL), washed with water (2 x 20 mL) and brine (10 mL) then dried over Na2S04 and concentrated to give a residue which was purified by flash chromatography on silica gel (eluting with petroleum ether/EtOAc 100/0 gradually increasing to 60/40) to give 7-chloro-l-ethyl-3-(2-fluoro-6-methoxyphenyl)-l,6-naphthyridin-2(lH)- imine (800 mg, 26%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6): delta 8.41 (s, 1H), 7.51 (q, J= 8.0 Hz, 1H), 7.41 (d, J= 10.6 Hz, 2H), 7.07-6.92 (m, 2H), 4.26 (m, 2H), 3.77 (d, J = 2.4 Hz, 3H), 1.22-1.16 (m, 3H). MS [ESI, MH+] = 332.09.

Reference： [1]Patent: WO2014/52365,2014,A1 .Location in patent: Page/Page column 299-300

2
[ 773837-37-9 ]
[ 146137-74-8 ]
[ 500912-18-5 ]

Yield	Reaction Conditions	Operation in experiment
46%	In ethanol; at 80℃; for 4h;	To a solution of Scheme 56 compound 3 (5.7 g, 26.15 mmol) in dry EtOH (70 mL) was added NaCN (1.4 g, 28.76 mmol) and the reaction mixture was stirred at 80 C for 4 h. After TLC showed the starting material was completely consumed, the reaction mixture was concentrated to give a crude compound which was diluted with ice water (30 mL) and extracted with EtOAc (2 x 50 mL). The organic layer was washed with brine (20 mL), dried over Na2S04 and concentrated to give a residue which was purified by column chromatography (eluting with petroleum ether/EtOAc 100/0 gradually increasing to 60/40) to give Scheme 56 compound 4 (2.0 g, 46%) as a colorless liquid. MS [ESI, MH+] = 166.06.

Reference： [1]Patent: WO2014/52365,2014,A1 .Location in patent: Page/Page column 299-300

3
2-fluoro-6-methoxybenzyl alcohol [ No CAS ]
[ 500912-18-5 ]

Reference： [1]Patent: WO2014/52365,2014,A1

4
[ 137654-21-8 ]
[ 500912-18-5 ]

Reference： [1]Patent: WO2014/52365,2014,A1

5
[ 500912-18-5 ]
[ 1588423-04-4 ]

Reference： [1]Patent: WO2014/52365,2014,A1

6
[ 500912-18-5 ]
[ 1588424-21-8 ]

Reference： [1]Patent: WO2014/52365,2014,A1

7
[ 500912-18-5 ]
[ 1588424-24-1 ]

Reference： [1]Patent: WO2014/52365,2014,A1

8
[ 500912-18-5 ]
1'-benzyl-4-fluoro-2H-spiro[benzofuran-3,4'-piperidine]-2-one hydrobromide [ No CAS ]

Reference： [1]Patent: EP3480198,2019,A1

9
[ 500912-18-5 ]
[ 10429-82-0 ]
1-benzyl-4-(2-fluoro-6-methoxyphenyl)piperidine-4-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
132 mg		First, sodium bis(trimethylsilyl) amide (1.0 M tetrahydrofuran solution) (1.6 mL) was added dropwise to a solution of <strong>[500912-18-5]2-<strong>[500912-18-5](2-fluoro-6-methoxyphenyl)acetonitrile</strong></strong> (86 mg) in tetrahydrofuran (2.4 mL) under ice cooling, and the mixture was stirred at the same temperature for 30 minutes. N-benzyl-bis(2-chloroethyl)amine hydrochloride (140 mg) was added to the resultant solution, followed by reflux for 2 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and then was dried with anhydrous magnesium sulfate. the solvent was removed by evaporation under reduced pressure. The obtained residue was purified by silica gel column chromatography (diethylether/n-hexane = 50/50) to obtain 1-benzyl-4-(2-fluoro-6-methoxyphenyl)piperidine-4-carbonitr ile (132 mg). 1H-NMR (400MHz, CDCl3) delta: 2.28-2.37(m,2H),2.43-2.50(m,2H),2.50-2.59(m,2H),2.89-2.98(m ,2H),3.58(s,2H),3.91(s,3H),6.67(ddd,J=12.9,8.4,1.2Hz,1H),6. 74(d,J=8.3Hz,1H),7.21-7.29(m,3H),7.29-7.36(m,4H).

Reference： [1]Patent: EP3480198,2019,A1 .Location in patent: Paragraph 0225; 0226

10
[ 24424-99-5 ]
[ 500912-18-5 ]
(+/-)-tert-butyl cyano(2-fluoro-6-methoxyphenyl)acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
10.4 g		[0473] Under argon and at -65C., a 2 M solution of LDA in THF (23 ml, 45 mmol) was added slowly to a solution of <strong>[500912-18-5](2-fluoro-6-methoxyphenyl)acetonitrile</strong> (5.00 g, 30.3 mmol, CAS-RN 500912-18-5) in THF (25 ml), and the mixture was allowed to warm to 0C. and, after 15 min, once more cooled to -65C. Subsequently, a solution of di-tert-butyl dicarbonate (10 ml, 45 mmol) in THF (11 ml) was slowly added dropwise, keeping the internal temperature below -40C. The mixture was stirred overnight, with the temperature gradually rising to RT. With ice cooling and stirring, 1 M hydrochloric acid (45.4 ml, 45.4 mmol) was then slowly added to the mixture, followed by water (30 ml) and ethyl acetate (80 ml). After agitation and phase separation, the aqueous phase was extracted once with ethyl acetate (80 ml). The combined organic phases were dried over sodium sulfate, filtered and concentrated, and the residue was taken up in dichloromethane and purified by flash column chromatography (500 g of silica gel, cyclohexane/ethyl acetate 10:1). The combined target fractions were concentrated, and the residue was dried under reduced pressure. This gave 10.4 g (62% purity, 80% of theory) of the title compound. [0474] LC-MS (Method 1): Rt=1.89 min; MS (ESIpos): m/z=266 [M+H]+

Reference： [1]Patent: US2020/31775,2020,A1 .Location in patent: Paragraph 0472-0474

11
[ 5292-43-3 ]
[ 500912-18-5 ]
(+/-)-tert-butyl 3-cyano-3-(2-fluoro-6-methoxyphenyl)propanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
11.4 g		[0549] To a solution of <strong>[500912-18-5](2-fluoro-6-methoxyphenyl)acetonitrile</strong> (5.00 g, 30.3 mmol) in THF (50 ml) under argon was added gradually while stirring, at -78 to -60C., a 2 M solution of LDA in THF (23 ml, 45 mmol). The mixture was allowed to come to 0C. and, after 15 min, cooled back down again to -78C. Subsequently, tert-butyl bromoacetate (6.7 ml, 45 mmol) was slowly added dropwise thereto at -78 to -60C. while stirring. The cooling bath was removed and, with stirring, the mixture was allowed to slowly warm to RT. After 4 h, at 0C., water and ethyl acetate (50 ml each) were added, the mixture was agitated and the phases were separated. The aqueous phase was extracted once with ethyl acetate (50 ml). The combined organic phases were washed once with saturated aqueous sodium chloride solution (100 ml), dried over sodium sulfate, filtered and concentrated, and the residue was dried under reduced pressure. This gave 11.4 g (93% purity, 100% of theory, comprises further impurities) of the title compound. [0550] LC-MS (Method 1): Rt=2.00 min; MS (ESIpos): m/z=280 [M+H]+ [0551] 1H-NMR (400 MHz, DMSO-d6) delta [ppm]: 1.334 (16.00), 1.397 (0.78), 1.425 (3.42), 2.844 (0.47), 2.862 (0.47), 2.999 (0.42), 3.020 (0.42), 3.309 (3.17), 4.017 (0.76), 4.635 (0.44), 6.894 (0.43), 6.958 (0.53), 6.980 (0.58), 7.402 (0.46), 7.419 (0.45). [0552] 1H-NMR (400 MHz, DMSO-d6): delta [ppm]=7.41 (dd, 1H), 6.97 (d, 1H), 6.89 (t, 1H), 4.63 (dd, 1H), 3.89 (s, 3H), 3.03 (dd, 1H), 2.83 (dd, 1H), 1.33 (s,9H).

Reference： [1]Patent: US2020/31775,2020,A1 .Location in patent: Paragraph 0548-0552

12
[ 500912-18-5 ]
[ 74-88-4 ]
(+/-)-2-(2-fluoro-6-methoxyphenyl)propanenitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%		[0428] Under argon and at -78C., a mixture of 2.5 M butyllithium solution in hexane (13 ml, 33 mmol) and THF (50 ml) was added slowly to a solution of N,N-diisopropylethylamine (5.8 ml, 33 mmol) in THF (75 ml). The reaction mixture was allowed to warm to 0C., stirred at 0C. for 5 min and cooled back down again to -78C. A solution of <strong>[500912-18-5](2-fluoro-6-methoxyphenyl)acetonitrile</strong> (5.00 g, 30.3 mmol, CAS-RN 500912-18-5, commercially available) in THF (25 ml) was then added slowly. The reaction mixture was once more allowed to warm to 0C., stirred at 0C. for 5 min and cooled back down again to -78C. A solution of iodomethane (2.0 ml, 31.79 mmol) in THF (25 ml) was then added slowly. The mixture was stirred overnight, with the temperature gradually rising to RT. At 0C., saturated ammonium chloride solution and water (50 ml each) were then added and the mixture was shaken and extracted twice with ethyl acetate (150 ml each). The combined organic phases were washed once with saturated aqueous sodium chloride solution (200 ml), dried over sodium sulfate, filtered and concentrated, and the residue was taken up in dichloromethane and purified by flash column chromatography (400 g of silica gel Buchi Snap-Cartridge KP-Sil, cyclohexane/ ethyl acetate 9:1). The combined target fractions were concentrated, and the residue was (briefly) dried under reduced pressure. This gave 3.33 g (100% purity, 61% of theory) of the title compound. [0429] GC-MS (Method 12): Rt=4.31 min; MS (ESIpos): m/z=179 [M]+ [0430] 1H-NMR (400 MHz, DMSO-d6) delta [ppm]: 1.492 (15.85), 1.509 (16.00), 3.314 (9.13), 3.887 (0.90), 4.452 (0.69), 4.455 (0.70), 4.470 (2.12), 4.473 (2.10), 4.488 (2.11), 4.491 (2.05), 4.505 (0.69), 4.508 (0.65), 6.861 (1.62), 6.863 (1.60), 6.884 (2.45), 6.907 (1.81), 6.909 (1.81), 6.943 (3.36), 6.964 (3.72), 7.353 (1.56), 7.370 (1.87), 7.374 (2.99), 7.391 (3.02), 7.395 (1.60), 7.412 (1.36). [0431] 1H-NMR (400 MHz, DMSO-d6): 5 [ppm]=7.44-7.30 (m, 1H), 6.95 (d, 1H), 6.92-6.85 (m, 1H), 4.48 (qd, 1H), 3.88 (s, 3H), 1.50 (d,3H).

Reference： [1]Patent: US2020/31775,2020,A1 .Location in patent: Paragraph 0427-0431

13
[ 500912-18-5 ]
(+/-)-4-[(6-bromo-3-methyl-2-phenylquinolin-4-yl)carbonyl]amino}-3-(2-fluoro-6-methoxyphenyl)butanoic acid [ No CAS ]