[ CAS No. 1229236-86-5 ] {[proInfo.proName]}

Name: 1229236-86-5|3-(4-Chloro-2-fluorobenzyl)-2-methyl-N-(5-methyl-1H-pyrazol-3-yl)-8-(morpholinomethyl)imidazo[1,2-b]pyridazin-6-amine|98%
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SKU: A315267
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Quality Control of [ 1229236-86-5 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 1229236-86-5 ]

SDS Specification

Alternatived Products of [ 1229236-86-5 ]

Product Details of [ 1229236-86-5 ]

CAS No. :	1229236-86-5	MDL No. :	MFCD20482143
Formula :	C₂₃H₂₅ClFN₇O	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	SQSZANZGUXWJEA-UHFFFAOYSA-N
M.W :	469.94	Pubchem ID :	46213929
Synonyms :	LY2784544	Chemical Name :	3-(4-Chloro-2-fluorobenzyl)-2-methyl-N-(5-methyl-1H-pyrazol-3-yl)-8-(morpholinomethyl)imidazo[1,2-b]pyridazin-6-amine

Calculated chemistry of [ 1229236-86-5 ]

Physicochemical Properties

Num. heavy atoms :	33
Num. arom. heavy atoms :	20
Fraction Csp3 :	0.35
Num. rotatable bonds :	6
Num. H-bond acceptors :	6.0
Num. H-bond donors :	2.0
Molar Refractivity :	129.01
TPSA :	83.37 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	Yes
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	Yes
CYP2C9 inhibitor :	Yes
CYP2D6 inhibitor :	Yes
CYP3A4 inhibitor :	Yes
Log Kp (skin permeation) :	-6.48 cm/s

Lipophilicity

Log Po/w (iLOGP) :	3.25
Log Po/w (XLOGP3) :	3.78
Log Po/w (WLOGP) :	3.92
Log Po/w (MLOGP) :	3.18
Log Po/w (SILICOS-IT) :	4.29
Consensus Log Po/w :	3.68

Druglikeness

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

Water Solubility

Log S (ESOL) :	-5.19
Solubility :	0.00305 mg/ml ; 0.00000649 mol/l
Class :	Moderately soluble
Log S (Ali) :	-5.22
Solubility :	0.0028 mg/ml ; 0.00000596 mol/l
Class :	Moderately soluble
Log S (SILICOS-IT) :	-8.16
Solubility :	0.00000327 mg/ml ; 0.000000007 mol/l
Class :	Poorly soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	2.0
Synthetic accessibility :	3.92

Safety of [ 1229236-86-5 ]

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 [ 1229236-86-5 ]

* 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 [ 1229236-86-5 ]
Downstream synthetic route of [ 1229236-86-5 ]

[ 1229236-86-5 ] Synthesis Path-Upstream 1~7

1
[ 31230-17-8 ]
[ 1229236-86-5 ]

Yield	Reaction Conditions	Operation in experiment
22%	Stage #1: With sodium hydrogencarbonate In N,N-dimethyl-formamide at 150℃; for 1 h; Stage #2: With hydrogenchloride In 2-methyltetrahydrofuran; water Stage #3: With sodium hydroxide In butan-1-ol	Prepare active catalyst by combining palladium chloride (160 mg, 0.90 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (1.10 g, 1.84 mmol) in DMF (25 mL) and warming to form a solution. Add the preformed catalyst to a solution of 3-methyl-1H-pyrazol-5-amine (3.0 g, 29.65 mmol), 4-((6-chloro-3-(4-chloro-2-fluorobenzyl)-2-methylimidazo[1,2-b]pyridazin-8-yl)methyl)morpholine hydrochloride (9.0 g, 20.19 mmol), potassium bicarbonate (6.0 g, 59.93 mmol) in DMF (65 mL) and heat to 150° C. for 1 h. Cool the reaction to 60° C. and add mercaptopropyl functionalized silica (500 mg) and stir for 1 h then filter to remove the silica. Cool to ambient temperature, add 2-methyltetrahydrofuran (125 mL) and extract with water to remove DMF. Add HCl to the organic solution to form the 3-(4-chloro-2-fluorobenzyl)-2-methyl-N-(5-methyl-1H-pyrazol-3-yl)-8-(morpholinomethyl)imidazo[1,2-b]pyridazin-6-amine hydrochloride salt. Add the HCl salt (1.1 g) to sodium hydroxide (10 mL, 1N) in n-butanol (10 mL) and stir. Filter the resulting mixture to obtain 0.22 g of the free base, imidazo[1,2-b]pyridazin-6-amine, 3-[(4-chloro-2-fluorophenyl)methyl]-2-methyl-N-(5-methyl-1H-pyrazol-3-yl)-8-(4-morpholinylmethyl), (22percent yield, M+1.=470).

Reference： [1] Patent: US2010/152181, 2010, A1, . Location in patent: Page/Page column 5

2
[ 1346221-91-7 ]
[ 1229236-86-5 ]

Reference： [1] Organic Process Research and Development, 2012, vol. 16, # 1, p. 70 - 81

3
[ 1229236-85-4 ]
[ 1229236-86-5 ]

Reference： [1] Organic Process Research and Development, 2012, vol. 16, # 1, p. 70 - 81
[2] Organic Process Research and Development, 2012, vol. 16, # 1, p. 70 - 81

4
[ 1229236-79-6 ]
[ 1229236-86-5 ]

Reference： [1] Organic Process Research and Development, 2012, vol. 16, # 1, p. 70 - 81
[2] Organic Process Research and Development, 2012, vol. 16, # 1, p. 70 - 81

5
[ 1229236-83-2 ]
[ 1229236-86-5 ]

Reference： [1] Organic Process Research and Development, 2012, vol. 16, # 1, p. 70 - 81
[2] Organic Process Research and Development, 2012, vol. 16, # 1, p. 70 - 81

6
[ 1229236-80-9 ]
[ 1229236-86-5 ]

Reference： [1] Organic Process Research and Development, 2012, vol. 16, # 1, p. 70 - 81
[2] Organic Process Research and Development, 2012, vol. 16, # 1, p. 70 - 81

7
[ 175711-83-8 ]
[ 1229236-86-5 ]

Reference： [1] Organic Process Research and Development, 2012, vol. 16, # 1, p. 70 - 81
[2] Organic Process Research and Development, 2012, vol. 16, # 1, p. 70 - 81

[ 1229236-86-5 ] Synthesis Path-Downstream 1~11

1
3-(4-chloro-2-fluorobenzyl)-N-(1-(4-methoxybenzyl)-5-methyl-1H-pyrazol-3-yl)-2-methyl-8-(morpholinomethyl)imidazo[1,2-b]pyridazin-6-amine [ No CAS ]
[ 1229236-86-5 ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 1 3-(4-Chloro-2-fluorobenzyl)-2-methyl-N-(5-methyl-1H-pyrazol-3-yl)-8-(morpholinomethyl)imidazo[1,2-b]pyridazin-6-amine Combine 3-(4-chloro-2-fluorobenzyl)-N-(1-(4-methoxybenzyl)-5-methyl-1H-pyrazol-3-yl)-2-methyl-8-(morpholinomethyl)imidazo[1,2-b]pyridazin-6-amine (0.447 g, 0.76 mmol) and trifluoroacetic acid (10 mL) in a 20 mL microwave reactor tube. Seal with a crimp cap then heat in a microwave reactor at 120 C. for 20 min. Partition between EA and water that is made basic with excess NaOH aqueous. Wash the organic phase three times with NaOH aqueous followed by aqueous saturated sodium chloride. Dry over anhydrous magnesium sulfate. Filter and concentrate in vacuo. Purify on silica gel (EA?10% methanol:EA) to give the title compound (0.246 g, 0.52 mmol) as a pale yellow solid. LCMS (8 min)=470.0, M+1.

Reference： [1]Patent: US2010/152181,2010,A1 .Location in patent: Page/Page column 3-4

2
4-((6-chloro-3-(4-chloro-2-fluorobenzyl)-2-methylimidazo[1,2-b]pyridazin-8-yl)methyl)morpholine hydrochloride [ No CAS ]
[ 31230-17-8 ]
[ 1229236-86-5 ]

Yield	Reaction Conditions	Operation in experiment
22%		Prepare active catalyst by combining palladium chloride (160 mg, 0.90 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (1.10 g, 1.84 mmol) in DMF (25 mL) and warming to form a solution. Add the preformed catalyst to a solution of 3-methyl-1H-pyrazol-5-amine (3.0 g, 29.65 mmol), 4-((6-chloro-3-(4-chloro-2-fluorobenzyl)-2-methylimidazo[1,2-b]pyridazin-8-yl)methyl)morpholine hydrochloride (9.0 g, 20.19 mmol), potassium bicarbonate (6.0 g, 59.93 mmol) in DMF (65 mL) and heat to 150 C. for 1 h. Cool the reaction to 60 C. and add mercaptopropyl functionalized silica (500 mg) and stir for 1 h then filter to remove the silica. Cool to ambient temperature, add 2-methyltetrahydrofuran (125 mL) and extract with water to remove DMF. Add HCl to the organic solution to form the 3-(4-chloro-2-fluorobenzyl)-2-methyl-N-(5-methyl-1H-pyrazol-3-yl)-8-(morpholinomethyl)imidazo[1,2-b]pyridazin-6-amine hydrochloride salt. Add the HCl salt (1.1 g) to sodium hydroxide (10 mL, 1N) in n-butanol (10 mL) and stir. Filter the resulting mixture to obtain 0.22 g of the free base, imidazo[1,2-b]pyridazin-6-amine, 3-[(4-chloro-2-fluorophenyl)methyl]-2-methyl-N-(5-methyl-1H-pyrazol-3-yl)-8-(4-morpholinylmethyl), (22% yield, M+1.=470).

Reference： [1]Patent: US2010/152181,2010,A1 .Location in patent: Page/Page column 5

3
[ 1229236-86-5 ]
[ 1229236-87-6 ]

Yield	Reaction Conditions	Operation in experiment
100%	With hydrogenchloride; In 1,4-dioxane; at 20℃; for 1.5h;Inert atmosphere;	EXAMPLE 2 3-(4-Chloro-2-fluorobenzyl)-2-methyl-N-(5-methyl-1H-pyrazol-3-yl)-8-(morpholinomethyl)imidazo[1,2-b]pyridazin-6-amine hydrochloride Combine <strong>[1229236-86-5]3-(4-chloro-2-fluorobenzyl)-2-methyl-N-(5-methyl-1H-pyrazol-3-yl)-8-(morpholinomethyl)imidazo[1,2-b]pyridazin-6-amine</strong> (0.1 g, 0.21 mmol) and 1,4-dioxane (10 mL) in a pear flask and place under nitrogen. Add hydrogen chloride (4 M in 1,4-dioxane, 0.053 mL, 1.0 equiv.) and let stir at RT under nitrogen for 1.5 h. Concentrate in vacuo then evaporate under vacuum from absolute ethanol two times. Dry overnight in a vacuum oven (60 C.) to give the title compound (0.11 g, 102%). LCMS (8 min)=470.0, M+1.

Reference： [1]Patent: US2010/152181,2010,A1 .Location in patent: Page/Page column 4

4
[ 1229236-85-4 ]
[ 1229236-86-5 ]