[ CAS No. 108166-01-4 ]

Name: 108166-01-4|Methyl 2-methylquinoline-6-carboxylate|98%
Brand: Ambeed
SKU: A458157
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3d Animation Molecule Structure of 108166-01-4

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Quality Control of [ 108166-01-4 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 108166-01-4 ]

SDS Specification

Alternatived Products of [ 108166-01-4 ]

Product Details of [ 108166-01-4 ]

CAS No. :	108166-01-4	MDL No. :	MFCD02690144
Formula :	C₁₂H₁₁NO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	KGSIXOOGGCSYTB-UHFFFAOYSA-N
M.W :	201.22	Pubchem ID :	2308822
Synonyms :

Calculated chemistry of [ 108166-01-4 ]

Physicochemical Properties

Num. heavy atoms :	15
Num. arom. heavy atoms :	10
Fraction Csp3 :	0.17
Num. rotatable bonds :	2
Num. H-bond acceptors :	3.0
Num. H-bond donors :	0.0
Molar Refractivity :	57.99
TPSA :	39.19 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) :	-5.8 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.42
Log Po/w (XLOGP3) :	2.44
Log Po/w (WLOGP) :	2.33
Log Po/w (MLOGP) :	1.91
Log Po/w (SILICOS-IT) :	2.78
Consensus Log Po/w :	2.38

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.99
Solubility :	0.208 mg/ml ; 0.00103 mol/l
Class :	Soluble
Log S (Ali) :	-2.91
Solubility :	0.25 mg/ml ; 0.00124 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-4.17
Solubility :	0.0136 mg/ml ; 0.0000678 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.41

Safety of [ 108166-01-4 ]

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 [ 108166-01-4 ]

* 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 [ 108166-01-4 ]
Downstream synthetic route of [ 108166-01-4 ]

[ 108166-01-4 ] Synthesis Path-Upstream 1~6

1
[ 67-56-1 ]
[ 635-80-3 ]
[ 108166-01-4 ]

Yield	Reaction Conditions	Operation in experiment
59%	at 0 - 65℃; for 12 h;	Step 2: methyl 2-methylquinoline-6-carboxylate: To a solution of 2-methylquinoline-6- carboxylic acid (3.0 g, 16.20 mmol) in methanol (30 ml.), sulphuric acid ( 3ml) was added dropwise at 0°C and then stirred at 65°C for 12h. The reaction mixture was concentrated and to the residue dichloromethane and aqueous sodium carbonate solutions were added. The organic layer was dried with sodium sulphate and concentrated to afford the title compound as a brown solid (1.9 g, 59percent).
59%	at 0 - 65℃; for 12 h;	Step 2: methyl 2-methylquinoline-6-carboxylate To a solution of 2-methylquinoline-6-carboxylic acid (3.0 g, 16.20 mmol) in methanol (30 ml.), sulphuric acid (3 ml) was added dropwise at 0° C. and then stirred at 65° C. for 12 h. The reaction mixture was concentrated and to the residue dichloromethane and aqueous sodium carbonate solutions were added. The organic layer was dried with sodium sulphate and concentrated to afford the title compound as a brown solid (1.9 g, 59percent).

Reference： [1] Journal of Heterocyclic Chemistry, 1989, vol. 26, p. 929 - 931
[2] Angewandte Chemie - International Edition, 2016, vol. 55, # 40, p. 12224 - 12227[3] Angew. Chem., 2016, vol. 128, # 40, p. 12412 - 12415,4
[4] Patent: WO2013/144737, 2013, A2, . Location in patent: Paragraph 252
[5] Patent: US2015/57309, 2015, A1, . Location in patent: Paragraph 0525
[6] Patent: WO2015/49535, 2015, A1, . Location in patent: Paragraph 00321

2
[ 598-32-3 ]
[ 17012-22-5 ]
[ 108166-01-4 ]

Reference： [1] Organic Letters, 2017, vol. 19, # 10, p. 2494 - 2497

3
[ 109-92-2 ]
[ 619-45-4 ]
[ 108166-01-4 ]

Reference： [1] Angewandte Chemie - International Edition, 2011, vol. 50, # 33, p. 7670 - 7673

4
[ 19718-49-1 ]
[ 108166-01-4 ]

Reference： [1] Organic and Biomolecular Chemistry, 2017, vol. 15, # 30, p. 6349 - 6352

5
[ 150-13-0 ]
[ 108166-01-4 ]

Reference： [1] Patent: WO2013/144737, 2013, A2,
[2] Patent: US2015/57309, 2015, A1,

6
[ 635-80-3 ]
[ 108166-01-4 ]

Reference： [1] J. Gen. Chem. USSR (Engl. Transl.), 1987, vol. 57, p. 96 - 99[2] Zhurnal Obshchei Khimii, 1987, vol. 57, # 1, p. 113 - 117

[ 108166-01-4 ] Synthesis Path-Downstream 1~4

1
[ 67-56-1 ]
[ 635-80-3 ]
[ 108166-01-4 ]

Yield	Reaction Conditions	Operation in experiment
59%	With sulfuric acid; at 0 - 65℃; for 12h;	Step 2: methyl 2-methylquinoline-6-carboxylate: To a solution of 2-methylquinoline-6- carboxylic acid (3.0 g, 16.20 mmol) in methanol (30 ml.), sulphuric acid ( 3ml) was added dropwise at 0C and then stirred at 65C for 12h. The reaction mixture was concentrated and to the residue dichloromethane and aqueous sodium carbonate solutions were added. The organic layer was dried with sodium sulphate and concentrated to afford the title compound as a brown solid (1.9 g, 59%).
59%	With sulfuric acid; at 0 - 65℃; for 12h;	Step 2: methyl 2-methylquinoline-6-carboxylate To a solution of <strong>[635-80-3]2-methylquinoline-6-carboxylic acid</strong> (3.0 g, 16.20 mmol) in methanol (30 ml.), sulphuric acid (3 ml) was added dropwise at 0 C. and then stirred at 65 C. for 12 h. The reaction mixture was concentrated and to the residue dichloromethane and aqueous sodium carbonate solutions were added. The organic layer was dried with sodium sulphate and concentrated to afford the title compound as a brown solid (1.9 g, 59%).
	With hydrogenchloride; In 1,4-dioxane; at 20 - 80℃; for 7h;Inert atmosphere;	[00321] To a solution of <strong>[635-80-3]2-methylquinoline-6-carboxylic acid</strong> (1 .5 g, 8.01 mmol) in dry methanol (18 mL) under argon at room temperature, HCI in dioxane (8.01 ml_, 32.1 mmol) was added dropwise and the resulting mixture was heated at 85C for 7 hours. Then it was cooled, concentrated, diluted with ethyl acetate and washed with NaOH 1 N (2 x 20 mL), water (1 x 20 mL) and brine (1 x 20 mL). Dried over Na2S04, filtered and concentrated under vacuum to afford the crude product methyl-2-methylquinoline-6- carboxylate as a pink solid (1 .44 g, 89%) which was carried onto the next step without purification. To a suspension of selenium dioxide (0.873 g, 7.87 mmol) in dry dioxane (1 1 mL) under argon at room temperature methyl-2-methylquinoline-6-carboxylate (1 .44 g, 7.16 mmol) was added in one portion and the resulting suspension was allowed to stir at 80 C for 18 hours. The reaction was allowed to cool to room temperature, filtered through Celite and concentrated under vacuum to afford an orange solid as crude product which was purified via flash column chromatography on silica gel in gradient from 10 to 20% ethyl acetate in petroleum ether to afford the clean product as a pale yellow solid (1 .28 g, 83%).

Reference： [1]Journal of Heterocyclic Chemistry,1989,vol. 26,p. 929 - 931
[2]Angewandte Chemie - International Edition,2016,vol. 55,p. 12224 - 12227
Angew. Chem.,2016,vol. 128,p. 12412 - 12415,4
[3]Patent: WO2013/144737,2013,A2 .Location in patent: Paragraph 252
[4]Patent: US2015/57309,2015,A1 .Location in patent: Paragraph 0525
[5]Patent: WO2015/49535,2015,A1 .Location in patent: Paragraph 00321

2
[ 635-80-3 ]
[ 108166-01-4 ]

Reference： [1]Journal of general chemistry of the USSR,1987,vol. 57,p. 96 - 99
Zhurnal Obshchei Khimii,1987,vol. 57,p. 113 - 117

Yield	Reaction Conditions	Operation in experiment
1: 70% 2: 18%	Stage #1: pentacarbonyl(1-[N-(4-methoxycarbonyl-2-ethenylphenyl)amino]ethylidene)chromium In hexane for 6h; Heating; Stage #2: With air for 14h;

4
[ 108166-01-4 ]
[ 73013-69-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: ammonium hydroxide / methanol / 12 h / 45 °C 2: triethylamine; trifluoroacetic anhydride / chloroform / 1.5 h / 10 °C
	Multi-step reaction with 2 steps 1: ammonium hydroxide / methanol / 12 h / 45 °C 2: trifluoroacetic anhydride; triethylamine / chloroform / 1.5 h / 10 °C

Reference： [1]Current Patent Assignee: ALEMBIC PHARMACEUTICALS LIMITED - WO2013/144737, 2013, A2
[2]Current Patent Assignee: ALEMBIC PHARMACEUTICALS LIMITED - US2015/57309, 2015, A1

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Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
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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.
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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.
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P285	In case of inadequate ventilation wear respiratory protection.
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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:
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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.
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P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
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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.
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P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
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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.
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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.
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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. 108166-01-4 ]

Quality Control of [ 108166-01-4 ]

Related Doc. of [ 108166-01-4 ]

Product Details of [ 108166-01-4 ]

Calculated chemistry of [ 108166-01-4 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 108166-01-4 ]

Application In Synthesis of [ 108166-01-4 ]

[ 108166-01-4 ] Synthesis Path-Upstream 1~6

[ 108166-01-4 ] Synthesis Path-Downstream 1~4

Related Functional Groups of [ 108166-01-4 ]

Esters

Related Parent Nucleus of [ 108166-01-4 ]

Quinolines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 108166-01-4 ]

Related Parent Nucleus of
[ 108166-01-4 ]