[ CAS No. 40117-63-3 ] {[proInfo.proName]}

Name: 40117-63-3|Quinuclidine-4-carboxylic acid hydrochloride|98%
Brand: Ambeed
SKU: A151736
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Structure of 40117-63-3 * Storage: {[proInfo.prStorage]}

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Quality Control of [ 40117-63-3 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 40117-63-3 ]

SDS Specification

Alternatived Products of [ 40117-63-3 ]

Product Details of [ 40117-63-3 ]

CAS No. :	40117-63-3	MDL No. :	MFCD10001479
Formula :	C₈H₁₄ClNO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	JTYXRFSULOZNPH-UHFFFAOYSA-N
M.W :	191.66	Pubchem ID :	66737825
Synonyms :

Calculated chemistry of [ 40117-63-3 ]

Physicochemical Properties

Num. heavy atoms :	12
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.88
Num. rotatable bonds :	1
Num. H-bond acceptors :	3.0
Num. H-bond donors :	1.0
Molar Refractivity :	51.63
TPSA :	40.54 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-8.35 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	-1.24
Log Po/w (WLOGP) :	0.98
Log Po/w (MLOGP) :	1.0
Log Po/w (SILICOS-IT) :	0.78
Consensus Log Po/w :	0.31

Druglikeness

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

Water Solubility

Log S (ESOL) :	-0.18
Solubility :	126.0 mg/ml ; 0.659 mol/l
Class :	Very soluble
Log S (Ali) :	0.88
Solubility :	1470.0 mg/ml ; 7.66 mol/l
Class :	Highly soluble
Log S (SILICOS-IT) :	-0.5
Solubility :	60.2 mg/ml ; 0.314 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.67

Safety of [ 40117-63-3 ]

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 [ 40117-63-3 ]

* 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 [ 40117-63-3 ]
Downstream synthetic route of [ 40117-63-3 ]

[ 40117-63-3 ] Synthesis Path-Upstream 1~1

1
[ 26458-78-6 ]
[ 40117-63-3 ]

Yield	Reaction Conditions	Operation in experiment
100%	With hydrogenchloride In water for 16 h; Reflux	Quinuclidine-4-carbonitrile (4 g, 29.4 mmol) was treated with 30 mL of 6 N aqueous HCl solution and stirred under reflux for 16 hr. The reaction mixture was cooled and evaporated to dryness under reduced pressure. The solid obtained was triturated with 20percent ether-hexane to afford the HCl salt of quinuclidine-4-carboxylic acid (5.5 g, quantitative).

Reference： [1] Patent: US2016/9706, 2016, A1, . Location in patent: Paragraph 0193

[ 40117-63-3 ] Synthesis Path-Downstream 1~40

3
[ 79-37-8 ]
[ 40117-63-3 ]
quinuclidin-4-ylcarbonyl chloride hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In N-methyl-acetamide; dichloromethane;	Step 4. Quinuclidin-4-ylcarbonyl chloride hydrochloride Quinuclidine-4-carboxylic acid hydrochloride (0.192 g, 0.001 mole) was suspended in dichloromethane (5 ml) and dimethylformamide (1 drop) and oxalyl chloride (0.436 ml. 0.635 g, 0.005 mole) were added. The resulting suspension was heated to reflux under an atmosphere of argon for six hours. Following concentration of the suspension in vacuo the residue was suspended in dichloromethane, concentrated in vacuo and finally dried in vacuo to give the title compound as a pale brown solid.

Reference： [1]Patent: US6281226,2001,B1

4
[ 40117-63-3 ]
[ 26608-58-2 ]

Yield	Reaction Conditions	Operation in experiment
4.04 g, (91%)	With sodium hydroxide; In tetrahydrofuran; water;	Step 1. Quinuclidin-4-ylmethanol Quinuclidine-4-carboxylic acid hydrochloride (6.0 g, 0.03 1 mmoles) in tetrahydrofuran (300 ml) was treated with lithium aluminum hydride (5.0 g, 0.137 mmoles) at ambient temperature for 18 hours. Water (20 ml) and 10% aqueous sodium hydroxide (7.5 ml) was added carefully and the mixture filtered, washing with diethyl ether. The combined filtrates were evaporated to dryness to give the title compound as a white solid 4.04 g, (91%): MS (+ve ion electrospray) m/z 142 (MH+, 100%)
	With dimethylsulfide borane complex; In tetrahydrofuran; at 0 - 20℃;Heating / reflux;	Example 1(Quinuclidin-4-yl)methanol (Quinuclidin-4-yl)carboxylic acid was prepared from 4-cyanoquinuclidine (Oakwood Products) following the procedure of Grob and Renk, Helv. Chim. Acta, 37, 1681 (1954).To a stirred suspension of <strong>[40117-63-3]quinuclidine-4-carboxylic acid hydrochloride</strong> (100 mg, 0.523 mmol) in 3 mL of anhydrous tetrahydrofuran at 0 C. was added borane methylsulfide complex (42 mg, 0.553 mmol). The mixture was stirred at room temperature for 1 hr and heated to reflux overnight. The reaction was cooled to 0 C. and carefully treated with 1 mL of methanol. The solvent was then removed under reduced pressure to leave the desired alcohol. Yield 36 mg. MS (m/e): 141.
36 mg	With dimethylsulfide borane complex; In tetrahydrofuran; at 0℃;Reflux;	(Quinuclidin-4-yl)carboxylic acid was prepared from 4-cyanoquinuclidine (Oakwood Products) following the procedure of Grob and Renk, Helv. Chim. Acta, 37, 1681 (1954). To a stirred suspension of <strong>[40117-63-3]quinuclidine-4-carboxylic acid hydrochloride</strong> (100 mg, 0.523 mmol) in 3 mL of anhydrous tetrahydrofuran at 0 C. was added borane methylsulfide complex (42 mg, 0.553 mmol). The mixture was stirred at room temperature for 1 hr and heated to reflux overnight. The reaction was cooled to 0 C. and carefully treated with 1 mL of methanol. The solvent was then removed under reduced pressure to leave the desired alcohol. Yield 36 mg. MS (m/e): 141.

Reference： [1]Patent: US6281226,2001,B1
[2]Patent: US2009/88418,2009,A1 .Location in patent: Page/Page column 20
[3]Patent: US2016/9706,2016,A1 .Location in patent: Paragraph 0190; 0191

5
[ 26458-78-6 ]
[ 40117-63-3 ]
[ 26608-58-2 ]

Yield	Reaction Conditions	Operation in experiment
2.24 g (100%)	In tetrahydrofuran;	Step 1. Quinuclidin-4-ylmethanol Quinuclidine-4-carboxylic acid hydrochloride (3.0 g, 0.016 moles) was treated with lithium aluminium hydride (2.5 g, 0.066 moles) in tetrahydrofuran (150 ml) at ambient temperature for 18 hours. The reaction was worked up as in the method of Example 25 Step 1 to give the title compound 2.24 g (100%). MS (+ve electrospray) m/z 142 (MH+, 100%).

Reference： [1]Patent: US6281226,2001,B1

6
[ 456-47-3 ]
[ 40117-63-3 ]
[ 1404055-22-6 ]

Reference： [1]Patent: US2012/276018,2012,A1

7
[ 456-47-3 ]
[ 40117-63-3 ]
[ 1404055-21-5 ]

Yield	Reaction Conditions	Operation in experiment
29.8%		Preparation of 3-fluorobenzyl quinuclidine-4-carboxylate (compound 91)A mixture of <strong>[40117-63-3]quinuclidine-4-carboxylic acid hydrochloride</strong> (100 mg, 0.52 mmol) and thionyl chloride (500 mu, 6.85 mmol) was refluxed for 2 hours. The reaction was cooled at room temperature and the solvent was accurately removed. The residue was suspended in dry DCM and treated with (3-fluorophenyl)methanol (65.8 mg, 0.52 mmol). The reaction was stirred at room temperature for 24 hours. The solvent was evaporated, the residue was dissolved in water (1 ml), basified with NaHCO3 and extracted twice with EtOAc. The combined organic layers were dried over Na2SO4, filtered and evaporated to obtain 3-fluorobenzyl quinuclidine-4-carboxylate (41 mg, 29.8 % yield), which was used in the next step without any further purification.
		1. Preparation of 3-fluorobenzyl quinuclidine-4-carboxylate (Compound 91). A mixture of <strong>[40117-63-3]quinuclidine-4-carboxylic acid hydrochloride</strong> (100 mg, 0.52 mmol) and thionyl chloride (500 mul, 6.85 mmol) was refluxed for 2 hours. The reaction was cooled to room temperature, and the solvent was accurately removed. The residue was suspended in dry DCM and treated with (3-fluorophenyl)methanol (65.8 mg, 0.52 mmol). The reaction was stirred at room temperature for 24 hours. The solvent was evaporated, and the residue was dissolved in water (1 ml), basified with NaHCO3 and extracted twice with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and evaporated to obtain 3-fluorobenzyl quinuclidine-4-carboxylate (41 mg, 29.8% yield), which was used in the next step without any further purification.

Reference： [1]Patent: WO2012/146515,2012,A1 .Location in patent: Page/Page column 97
[2]Patent: US2012/276018,2012,A1 .Location in patent: Page/Page column 38

8
[ 87-69-4 ]
[ 1609191-01-6 ]
[ 40117-63-3 ]
[ 1609190-93-3 ]

Yield	Reaction Conditions	Operation in experiment
		Step 5: (S)-4-((1-(5-(2-methoxyquinolin-1-ium-3-yl)-JH-imidazol-2-yl)- 7-(methylamino)- 7-oxoheptyl)carbamoyl)quinuclidin-1-ium mono L-tartrate salt (A5) A solution of <strong>[40117-63-3]4-carboxyquinuclidin-1-ium chlorhydrate</strong> (1.3 eq.) in DMF (0.2 M) was treated with TBTU (1.3 eq.) and NMM (2.6 eq.). The reaction mixture was stirred at room temperature for 10 minutes and then added to a solution of A4 in DMF (0.2 M). The reaction was stirred at RT for 2 h and subsequently was purified by RP-HPLC (Acetonitrile/H20 + 0.1 % TFA). Theproduct was obtained as TFA salt which was partitioned between DCM and sat. aq. NaHCO3. The organic phase was separated, dried over Na2504 and concentrated under reduced pressure. The resulting syrup was dissolved in acetonitrile/H20 (2:3) and treated with L-tartaric acid (1 eq.). The resulting solution was lyophilized to obtain the title compound. 1H-NMR (400 MHz, 300 K, DMSO-d6) oe 8.73 (br s, 1H), 7.94 (t, 2H, J 9.6 Hz), 7.76 (d, 1H, J 8.0 Hz), 7.67 (br s,1H), 7.60 (m, 2H), 7.42 (t, 1H, J8.0 Hz), 5.02 (m, 1H), 4.13 (s, 3H), 3.93 (s, 2H), 3.18 (t, 6H, J7.2 Hz), 2.54 (d, 3H, J4.4 Hz), 2.05-1.91 (m, 8H), 1.51-1.23 (m, 8H). MS (ESj C29H38N603:519 (M+H).

Reference： [1]Patent: WO2014/67985,2014,A1 .Location in patent: Page/Page column 26

9
[ 87-69-4 ]
[ 1609191-15-2 ]
[ 40117-63-3 ]
[ 1609190-94-4 ]

Yield	Reaction Conditions	Operation in experiment
		Step 5: (S)-4-((1-(5-(6-methoxynaphthalen-2-yl)-JH-imidazol-3-ium-2-yl)- 7-(methylamino)- 7-oxoheptyl)carbamoyl)quinuclidin-1-ium mono L-tartrate salt (E5) A solution of <strong>[40117-63-3]4-carboxyquinuclidin-1-ium chlorhydrate</strong> (1.3 eq.) in DMF (0.2 M) was treated with TBTU (1.3 eq.) and NMM (2.6 eq.). The reaction mixture was stirred at room temperature for 10 mm and then added to a solution of E4 in DMF (0.2 M). The reaction was stirred at RT for 2 h, then filtered and purified by RP-HPLC (CH3CN/H20 + 0.1 % TFA). The product was obtained as TFA salt which was partitioned between EtOAc and sat. aq. NaHCO3. The organicphase was separated, dried (Na2504) and concentrated under reduced pressure. The resulting pale yellow solid was dissolved in acetonitrile/H20 (1:1) and treated with L-tartaric acid (1 eq.). The resulting solution was lyophilized to obtain the title compound. (400 MHz, 300K, DMSOd 6) oe: 11.5 (br s, 1H), 8.14 (br s, 1H), 7.95-7.73 (m, 4H), 7.66 (m, 1H), 7.54 (m, 1H), 7.27 (d, 1H, J2 Hz), 7.12 (dd, 1H, J8.8 and 2.4 Hz), 4.99 (m, 1H), 3.89 (s, 2H), 3.86 (s, 3H), 3.16 (m,6H), 2.54 (d, J4.4 Hz), 3H), 2.02 (t, 2H, J7.4 Hz), 2.01 (m, 6H), 1.83 (m, 2H), 1.48 (m, 2H),1.35-1.15 (m, 4H). MS (ESj C30H39N503: 518 (M+H).

Reference： [1]Patent: WO2014/67985,2014,A1 .Location in patent: Page/Page column 33

10
[ 87-69-4 ]
[ 1609191-20-9 ]
[ 40117-63-3 ]
[ 1609190-96-6 ]

Yield	Reaction Conditions	Operation in experiment
		Step 8: (S)-4- ((1- (5- (2-methoxyquinolin-1-ium-3-yl)oxazol-2-yl)- 7- (methylamino)- 7-oxoheptyl)carbamoyl)quinuclidin-1-ium mono L-tartrate salt (F8)A solution of <strong>[40117-63-3]4-carboxyquinuclidin-1-ium chlorhydrate</strong> (1.3 eq.) in DMF (0.1 M) was treated with HOBt (1.3 eq.), EDC HC1 (1.3 eq.) and DIPEA (1.3 eq.). The reaction mixture was stirred at room temperature for 10 minutes and then added to F7. The reaction was stirred for at RT for 48 h, filtered and directly purified by RP-HPLC (Acetonitrile/H20 + 0.1 % TFA). The product was obtained as TFA salt which was partitioned between DCM and sat. aq. NaHCO3. Theorganic phase was separated dried over Na2504 and concentrated under reduced pressure. The resulting solid was dissolved in acetonitrile/H20 (1:1) and treated with L-tartaric acid (1 eq.). The resulting solution was lyophilized to obtain the title compound. MS (ESj C29H37N504: 520 (M+H).

Reference： [1]Patent: WO2014/67985,2014,A1 .Location in patent: Page/Page column 36

11
[ 40117-63-3 ]
quinuclidin-4-ylmethyl 4-methoxy-5-methyl-1H-indole-3-carboxylate hydrochloride [ No CAS ]