[ CAS No. 121643-46-7 ]

Name: 121643-46-7|6-Chloro-2-methoxynicotinonitrile|97%
Brand: Ambeed
SKU: A202586
Price: 52.0 USD
Availability: InStock
Rating: 96 (28 reviews)

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

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

DV 2D 3D

3d Animation Molecule Structure of 121643-46-7

Structure of 121643-46-7 * Storage: {[proInfo.prStorage]}

Cart0 Add to My Favorites Bulk Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

For Research Only 88K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 121643-46-7 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 121643-46-7 ]

SDS

Alternatived Products of [ 121643-46-7 ]

Product Details of [ 121643-46-7 ]

CAS No. :	121643-46-7	MDL No. :	MFCD13659332
Formula :	C₇H₅ClN₂O	Boiling Point :	272.1±35.0°C at 760 mmHg
Linear Structure Formula :	-	InChI Key :	-
M.W :	168.58 g/mol	Pubchem ID :	14381111
Synonyms :

Calculated chemistry of of [ 121643-46-7 ]

Physicochemical Properties

Num. heavy atoms :	11
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.14
Num. rotatable bonds :	1
Num. H-bond acceptors :	3.0
Num. H-bond donors :	0.0
Molar Refractivity :	40.45
TPSA :	45.91 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) :	-6.02 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.93
Log Po/w (XLOGP3) :	1.84
Log Po/w (WLOGP) :	1.62
Log Po/w (MLOGP) :	0.52
Log Po/w (SILICOS-IT) :	1.94
Consensus Log Po/w :	1.57

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.38
Solubility :	0.699 mg/ml ; 0.00415 mol/l
Class :	Soluble
Log S (Ali) :	-2.42
Solubility :	0.634 mg/ml ; 0.00376 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.85
Solubility :	0.239 mg/ml ; 0.00142 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.92

Safety of [ 121643-46-7 ]

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

Application In Synthesis of [ 121643-46-7 ]

* 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 [ 121643-46-7 ]
Downstream synthetic route of [ 121643-46-7 ]

[ 121643-46-7 ] Synthesis Path-Upstream 1~6

1
[ 124-41-4 ]
[ 40381-90-6 ]
[ 121643-47-8 ]
[ 121643-46-7 ]

Reference： [1] Journal of the Chemical Society, Perkin Transactions 1, 1989, # 2, p. 283 - 287
[2] Patent: US2015/291629, 2015, A1, . Location in patent: Paragraph 0800
[3] Patent: CN108003161, 2018, A, . Location in patent: Paragraph 0489; 0491-0493

2
[ 67-56-1 ]
[ 124-41-4 ]
[ 40381-90-6 ]
[ 121643-46-7 ]

Yield	Reaction Conditions	Operation in experiment
19%	at 60℃; for 12 h;	To a stirred solution of 2,6-dichioronicotinonitrile (050 g, 2.89 mmoi) in MeOH (10 mL)was added sodium methanolate (0.62 g, 2.89 mmol) at ambient temperature. The reactionmixture was stirred at 60 °C for 12 h. The reaction mixture was cooled to ambient temperature and concentrated under reduced pressure, diluted with water (40 ml) and extracted with ethyl acetate (2 x 75 mL). The combined organic layers were washed with brine (50 mL), dried over sodium sulfate and evaporated under reduced pressure. The residue was purified by preparativeHPLC [Xbridge Phenyl (21.2 x 250 ID) 5 micron; Solvent A: 0.1percent TFA, Solvent B:Acetonitrile, Gradient: 5-25percent B over 25 mm, Flow: 20 mL/minj to 23A (0.48 g, 19percent) as an off white solid. ‘HNMR (400 MHz, CDCI3) ppm 4.08 (s, 3 H). 7.01 -- 7.03 (d, J= 7.2 Hz, I H), 7.80 7.82 (s, J= 8.0 Hz, IH). LCMS MethodD): retention time 1.94 mm, [M+H] 169.2.

Reference： [1] Patent: WO2018/93569, 2018, A1, . Location in patent: Page/Page column 100

3
[ 62068-78-4 ]
[ 121643-46-7 ]

Reference： [1] Patent: US2002/156087, 2002, A1,

4
[ 65515-28-8 ]
[ 121643-46-7 ]

Reference： [1] Patent: WO2016/54807, 2016, A1,

5
[ 38496-18-3 ]
[ 121643-46-7 ]

Reference： [1] Patent: WO2016/54807, 2016, A1,

6
[ 65515-32-4 ]
[ 121643-46-7 ]

Reference： [1] Patent: WO2016/54807, 2016, A1,

[ 121643-46-7 ] Synthesis Path-Downstream 1~25

1
[ 124-41-4 ]
[ 40381-90-6 ]
[ 121643-47-8 ]
[ 121643-46-7 ]

Yield	Reaction Conditions	Operation in experiment
1.64%; 19.70%	In methanol; at 60℃; for 12h;	To a solution of 2,6-dichloronicotinonitrile (0.50 g, 2.89 mmol) in MeOH (10 mL) was added sodium methoxide (0.62 g, 2.89 mmol) at ambient temperature and the resulting mixture was stirred at 60 C for 12 h. The reaction mixture was cooled to ambient temperature, concentrated to dryness under reduced pressure. The residue was diluted with water (50 mL) and extracted with ethyl acetate (3 x 50 mL). The combined organic layes were washed with brine (30 mL), dried over anhydrous sodium sulfate and evaporated under reduced pressure. The residue was purified by preparative HPLC [Xbridge Phenyl (250 x 21.2 ID) 5 micron; Solvent A: 0.1%TFA in water, Solvent B: Acetonitrile, Gradient: 0-100 % B over 20 min, Flow: 20 mL/min, UV 220 nm]. First eluted compound (retention time 15.34 min), designated as Intermediate 41A, was obtained (0.10 g, 19.70%) as white solid, 1H NMR (400 MHz, CDCl3) delta ppm 4.08 (s, 3 H), 7.02 (d, J = 7.83 Hz, 1 H), 7.82 (d, J = 7.83 Hz, 1 H). LCMS ( Method-D): retention time 1.94 min, [M+1H] 169.2. Second eluted compound (retention time 16.74 min), designated as Intermediate 41B, was obtained (0.04 g, 1.64%) as an off-white solid.1H NMR (400 MHz, DMSO-d6) delta ppm 3.95 (s, 3 H), 7.07 (s, 1 H), 8.29 (d, J = 8.53 Hz, 1 H). LCMS (Method-D): retention time 1.89 min, [M+1H] 169.2. Structure of Intermediate 41A and 41B was determined by single- crystal X-ray diffraction method.
	With methanol; at 0 - 20℃; for 16h;	6-Chloro-2-methoxy-nicotinonitrile and 2-Chloro-6-methoxy-nicotinonitrile (27 and 28) (0800) To a solution of 2,6-dichloro-nicotinonitrile (26, 5.0 g, 28.90 mmol) in methanol (25 mL) was added sodium methoxide (25% solution in methanol, 6.24 mL, 28.90 mmol) slowly at 0 C. and stirred for 16 h at room temperature. Methanol was distilled off and the residue was diluted with EtOAc (150 mL), washed with water (2×50 mL) and brine (50 mL), dried over Na2SO4, filtered, and concentrated to give crude mixture, which was recrystallized from ether to give inseparable mixture of compounds 27 and 28 in a ratio of 1:2 (4.8 g, quantitative) as white solid. 1H NMR 400 MHz (DMSO-d6) delta: 8.30 (d, J=8.2 Hz, 1H), 8.27 (d, J=8.6 Hz, 1H), 7.31 (d, J=7.7 Hz, 1H), 7.00 (d, J=8.6 Hz, 1H), 3.98 (s, 3H), 3.92 (s, 3H).
	In methanol; at 20℃; for 1h;Cooling with ice;	In the ice bath,Sodium metal (700 mg) was added to 30 mL of anhydrous methanol.Stir for one hour at room temperature until the sodium completely disappears.Stir at room temperatureThe above-mentioned new sodium methoxide solution,The solution was slowly added dropwise to a solution of 2,6-dichloro-3-cyanopyridine (5.0 g) in methanol (50 mL) via a constant pressure funnel.Reaction for 1 hour.Concentrate under reduced pressure,Add ethyl acetate to dissolve the residue,Insoluble sodium chloride precipitate is filtered off.The filtrate was concentrated to give a mixture of 6-chloro-2-methoxynicotinonitrile and 2-chloro-6-methoxynicotinonitrile (4.87 g).The results of nuclear magnetic profiling showed that the ratio of 6-chloro-2-methoxynicotinonitrile and 2-chloro-6-methoxynicotinonitrile was 2:1.Yellow solid.

Reference： [1]Patent: WO2018/222795,2018,A1 .Location in patent: Page/Page column 106
[2]Journal of the Chemical Society. Perkin transactions I,1989,p. 283 - 287
[3]Patent: US2015/291629,2015,A1 .Location in patent: Paragraph 0800
[4]Patent: CN108003161,2018,A .Location in patent: Paragraph 0489; 0491-0493

2
4-(2,4-dichlorophenyl)-5-imidazol-1-ylpyrimidin-2-ylethylamine [ No CAS ]
[ 121643-46-7 ]
6-[(2-[4-(2,4-dichlorophenyl)-5-imidazolylpyrimidin-2-yl]amino}ethyl)amino]-2-methoxypyridine-3-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Example 116 Preparation of 6-[(2-[4-(2,4-dichlorophenyl)-5-imidazolylpyrimidin-2-yl]amino}ethyl)amino]-2-methoxypyridine-3-carbonitrile 6-[(2-[4-(2,4-dichlorophenyl)-5-imidazolylpyrimidin-2-yl]amino}ethyl)amino]-2-methoxypyridine-3-carbonitrile was prepared from [4-(2,4-dichlorophenyl)-5-imidazol-1-ylpyrimidin-2-ylethylamine and <strong>[121643-46-7]6-chloro-2-methoxypyridine-3-carbonitrile</strong> in accordance with the procedure described above for the preparation of [4-(2,4-dichlorophenyl)-5-imidazol-2-ylpyrimidin-2-yl]{2-[(6-methoxy-5-nitro(2-pyridyl))amino]ethyl}amine. HPLC: 11.8 min (85% pure) MS: MH+=481.2 C22H18C12N8O 480 g/mol

Reference： [1]Patent: US2002/156087,2002,A1

3
[ 62068-78-4 ]
[ 121643-46-7 ]

Yield	Reaction Conditions	Operation in experiment
		Preparation of 6-chloro-2-methoxypyridine-3-carbonitrile 6-chloro-2-methoxypyridine-3-carbonitrile was prepared from 2,6-dichloro-pyridine-3-carboxamide in accordance with the procedure described above for the preparation of 6-chloro-2-methoxy-3-nitro-pyridine. HPLC: 11.37 min (80% pure) MS: MH+=169.1 C7H5C1N2O 168 g/mol

Reference： [1]Patent: US2002/156087,2002,A1

4
(4-bromo-3-methylphenyl)carbamic acid tert-butyl ester [ No CAS ]
[ 121643-46-7 ]
[ 1213790-37-4 ]

Yield	Reaction Conditions	Operation in experiment
49%		To a solution of tert-butyl 4-bromo-3-methylphenylcarbamate (4.36 g, 15.24 mmol) in N,N-dimethylformamide (60 mL) on an ice bath under a nitrogen balloon was added sodium hydride (0.610 g, 15.24 mmol). The reaction was stirred on an ice-water bath for 10 min. The ice bath was removed and to the solution was added a solution of <strong>[121643-46-7]6-chloro-2-methoxynicotinonitrile</strong> (3.85 g, 22.86 mmol) in N,N-dimethylformamide (40 mL) dropwise. After addition completed, the mixture was stirred overnight at 50 C. Water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, and dried on anhydrous sodium sulfate. The solvent was removed under reduced pressure to obtain the crude product. The crude was then purified by silica gel column (100% hexanes to 8:2 hexanes/ethyl acetate) to give tert-butyl 4-bromo-3-methylphenyl(5-cyano-6-methoxypyridin-2-yl)carbamate (3.15 g, 49%). 1H NMR (400 MHz, DMSO-d6) delta ppm 1.37 (s, 9H), 2.30 (s, 3H), 3.55 (s, 3H), 7.00 (dd, J=2.6, 8.4 Hz, 1H), 7.22 (d, J=2.5 Hz, 1H), 7.40 (d, J=8.5 Hz, 1H), 7.58 (d, J=8.4 Hz, 1H), 8.17 (d, J=8.4 Hz, 1H), 8.30 (d, J=8.0 Hz, 1H).

Reference： [1]Patent: US2011/166103,2011,A1 .Location in patent: Page/Page column 45-46

5
CH₄*C₁₃H₂₅NO₃ [ No CAS ]
[ 121643-46-7 ]
C₂₀H₂₉N₃O₄ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 7705 - 7712

6
[ 121643-46-7 ]
C₁₅H₂₁N₃O₂ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 7705 - 7712

7
[ 121643-46-7 ]
N-{trans-3-[(5-cyano-6-methoxypyridin-2-yl)oxy]-2,2,4,4-tetramethylcyclobutyl}imidazo[1,2-a]pyrimidine-3-carboxamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 7705 - 7712

8
4-bromo-3-(1,3-dioxolan-2-yl)-2-fluorophenol [ No CAS ]
[ 121643-46-7 ]
6-(4-bromo-3-(1,3-dioxolan-2-yl)-2-fluorophenoxy)-2-methoxynicotinonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With potassium carbonate; In N,N-dimethyl-formamide; at 80℃;	A solution of <strong>[121643-46-7]6-chloro-2-methoxynicotinonitrile</strong> (1.16 g, 6.88 mmol), 4-bromo-3-(1,3-dioxolan-2-yl)-2-fluorophenol (1.81 g, 6.88 mmol), potassium carbonate (1.14 g, 8.26 mmol), and N,N-dimethylformamide (35 mL) was stirred at 80 C. overnight. Water was added and the solution was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and filtered. The solvent was removed under reduced pressure and the residue was purified by silica gel column using Combiflash to give 6-(4-bromo-3-(1,3-dioxolan-2-yl)-2-fluorophenoxy)-2-methoxynicotinonitrile (2.31 g, 85% yield).

Reference： [1]Patent: US2015/291629,2015,A1 .Location in patent: Paragraph 1142

9
[ 121643-46-7 ]
6-(3-(1,3-dioxolan-2-yl)-2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)-2-methoxynicotinonitrile [ No CAS ]

Reference： [1]Patent: US2015/291629,2015,A1

10
[ 121643-46-7 ]
6-(2-fluoro-3-formyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)-2-methoxynicotinonitrile [ No CAS ]

Reference： [1]Patent: US2015/291629,2015,A1

11
[ 121643-46-7 ]
6-(4-fluoro-1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-5-yloxy)-2-methoxynicotinonitrile [ No CAS ]

Reference： [1]Patent: US2015/291629,2015,A1

12
[ 65515-28-8 ]
[ 121643-46-7 ]