[ CAS No. 796967-16-3 ] {[proInfo.proName]}

Name: 796967-16-3|1-(4-(3-Amino-1H-indazol-4-yl)phenyl)-3-(2-fluoro-5-methylphenyl)urea|98+%
Brand: Ambeed
SKU: A147574
Price: 19.0 USD
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Quality Control of [ 796967-16-3 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 796967-16-3 ]

SDS Specification

Alternatived Products of [ 796967-16-3 ]

Product Details of [ 796967-16-3 ]

CAS No. :	796967-16-3	MDL No. :	MFCD11840918
Formula :	C₂₁H₁₈FN₅O	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	MPVGZUGXCQEXTM-UHFFFAOYSA-N
M.W :	375.40	Pubchem ID :	11485656
Synonyms :	ABT-869;AL-39324	Chemical Name :	1-(4-(3-Amino-1H-indazol-4-yl)phenyl)-3-(2-fluoro-5-methylphenyl)urea

Calculated chemistry of [ 796967-16-3 ]

Physicochemical Properties

Num. heavy atoms :	28
Num. arom. heavy atoms :	21
Fraction Csp3 :	0.05
Num. rotatable bonds :	5
Num. H-bond acceptors :	3.0
Num. H-bond donors :	4.0
Molar Refractivity :	109.58
TPSA :	95.83 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	Yes
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	Yes
Log Kp (skin permeation) :	-5.85 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.0
Log Po/w (XLOGP3) :	3.86
Log Po/w (WLOGP) :	4.95
Log Po/w (MLOGP) :	3.75
Log Po/w (SILICOS-IT) :	3.58
Consensus Log Po/w :	3.63

Druglikeness

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

Water Solubility

Log S (ESOL) :	-4.82
Solubility :	0.00563 mg/ml ; 0.000015 mol/l
Class :	Moderately soluble
Log S (Ali) :	-5.57
Solubility :	0.00101 mg/ml ; 0.0000027 mol/l
Class :	Moderately soluble
Log S (SILICOS-IT) :	-8.25
Solubility :	0.00000213 mg/ml ; 0.0000000057 mol/l
Class :	Poorly soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	2.0
Synthetic accessibility :	2.81

Safety of [ 796967-16-3 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 796967-16-3 ]

* 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 [ 796967-16-3 ]
Downstream synthetic route of [ 796967-16-3 ]

[ 796967-16-3 ] Synthesis Path-Upstream 1~7

1
[ 599191-73-8 ]
[ 796967-18-5 ]
[ 796967-16-3 ]

Yield	Reaction Conditions	Operation in experiment
74.8%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; sodium carbonate In ethanol for 8 h; Reflux	The compound of Formula VI (10.6 g, 28.6 mmol) obtained in Example 3 was added sequentially to the reaction flask.3-amino-4-iodocarbazole(8.1 g, 31.3 mmol), sodium carbonate (7.6 g, 71.7 mmol), 100 mL of ethanol, 100 mL of water. PdCl2 (dppf) (0.4 g, 0.6 mmol) was added with stirring at room temperature and the temperature was increased to reflux. After refluxing for 8 hours, the ethanol was distilled off under reduced pressure. Ethyl acetate (150 mL) and a 20percent aqueous solution of ammonium chloride (50 mL) were added to the residue, followed by stirring for 30 minutes. The organic layer was separated, washed with water 3 times and dried over anhydrous sodium sulfate. The organic layer was evaporated to dryness under reduced pressure and the resulting crude product was recrystallized from dichloromethane-ethanol (10:1) to give 8.0 g of a white solid with a yield of 74.8percent. The purity by HPLC was 99.0percent. MS (ESI) m / z: (M + H) = 376.4.

Reference： [1] Patent: CN103570754, 2018, B, . Location in patent: Paragraph 0176-0179
[2] Organic Process Research and Development, 2009, vol. 13, # 6, p. 1419 - 1425
[3] Journal of Medicinal Chemistry, 2007, vol. 50, # 7, p. 1584 - 1597
[4] Chemical Communications, 2015, vol. 51, # 29, p. 6384 - 6387

2
[ 452-84-6 ]
[ 796967-16-3 ]

Reference： [1] Journal of Medicinal Chemistry, 2007, vol. 50, # 7, p. 1584 - 1597
[2] Patent: CN103570754, 2018, B,

3
[ 796967-18-5 ]
[ 20925-60-4 ]
[ 796967-16-3 ]

Reference： [1] Organic Process Research and Development, 2009, vol. 13, # 6, p. 1419 - 1425

4
[ 79544-29-9 ]
[ 796967-16-3 ]

Reference： [1] Journal of Medicinal Chemistry, 2007, vol. 50, # 7, p. 1584 - 1597

5
[ 214360-73-3 ]
[ 796967-16-3 ]

Reference： [1] Journal of Medicinal Chemistry, 2007, vol. 50, # 7, p. 1584 - 1597

6
[ 1145835-80-8 ]
[ 796967-16-3 ]

Reference： [1] Patent: WO2009/52231, 2009, A1, . Location in patent: Page/Page column 13-14

7
[ 214360-73-3 ]
[ 796967-16-3 ]

Reference： [1] Chemical Communications, 2015, vol. 51, # 29, p. 6384 - 6387

[ 796967-16-3 ] Synthesis Path-Downstream 1~41

1
[ 599191-73-8 ]
[ 796967-18-5 ]
[ 796967-16-3 ]

Yield	Reaction Conditions	Operation in experiment
74.8%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In ethanol; for 8h;Reflux;	The compound of Formula VI (10.6 g, 28.6 mmol) obtained in Example 3 was added sequentially to the reaction flask.3-amino-4-iodocarbazole(8.1 g, 31.3 mmol), sodium carbonate (7.6 g, 71.7 mmol), 100 mL of ethanol, 100 mL of water. PdCl2 (dppf) (0.4 g, 0.6 mmol) was added with stirring at room temperature and the temperature was increased to reflux. After refluxing for 8 hours, the ethanol was distilled off under reduced pressure. Ethyl acetate (150 mL) and a 20percent aqueous solution of ammonium chloride (50 mL) were added to the residue, followed by stirring for 30 minutes. The organic layer was separated, washed with water 3 times and dried over anhydrous sodium sulfate. The organic layer was evaporated to dryness under reduced pressure and the resulting crude product was recrystallized from dichloromethane-ethanol (10:1) to give 8.0 g of a white solid with a yield of 74.8percent. The purity by HPLC was 99.0percent. MS (ESI) m / z: (M + H) = 376.4.

Reference： [1]Patent: CN103570754,2018,B .Location in patent: Paragraph 0176-0179
[2]Organic Process Research and Development,2009,vol. 13,p. 1419 - 1425
[3]Journal of Medicinal Chemistry,2007,vol. 50,p. 1584 - 1597
[4]Chemical Communications,2015,vol. 51,p. 6384 - 6387

2
2-(4-isocyanatophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane [ No CAS ]
[ 796967-16-3 ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 1584 - 1597

3
[ 452-84-6 ]
[ 796967-16-3 ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 1584 - 1597
[2]Patent: CN103570754,2018,B

4
2-fluoro-5-methyl-phenylisocyanate [ No CAS ]
[ 796967-16-3 ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 1584 - 1597
[2]Patent: CN103570754,2018,B

5
[ 79544-29-9 ]
[ 796967-16-3 ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 1584 - 1597

6
[ 214360-73-3 ]
[ 796967-16-3 ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 1584 - 1597

7
[ 796967-16-3 ]
[ 108-88-3 ]
N-[4-(3-amino-1H-indazol-4-yl)phenyl]-N'-(2-fluoro-5-methylphenyl)urea toluenate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	at 110℃;	EXAMPLE 1; Preparation of <strong>[796967-16-3]ABT-869</strong> Tolueneate Crystalline FormThis example was prepared by recrystallizing <strong>[796967-16-3]ABT-869</strong> from toluene at about HO0C and filtering.

Reference： [1]Patent: WO2009/52230,2009,A1 .Location in patent: Page/Page column 13

8
N-[4-(3-amino-1H-indazol-4-yl)phenyl]-N'-(2-fluoro-5-methylphenyl)urea toluenate [ No CAS ]
[ 796967-16-3 ]

Yield	Reaction Conditions	Operation in experiment
	In acetonitrile;Heating / reflux;	EXAMPLE 2; Preparation of ABT-869 Crystalline Form 1A mixture of EXAMPLE 1 and acetonitrile was stirred at reflux until ABT-869 Crystalline Form 1 formed, and was then cooled and filtered.

Reference： [1]Patent: WO2009/52230,2009,A1 .Location in patent: Page/Page column 13

9
[ 1145835-80-8 ]
[ 796967-16-3 ]

Yield	Reaction Conditions	Operation in experiment
	Humidity 0 percent;	EXAMPLE 3; Preparation of ABT-869 Crystalline Form 2 <n="15"/>Filed electronically October 16, 2008A mixture of EXAMPLE 2 was stored under nitrogen at 0percent humidity.

Reference： [1]Patent: WO2009/52231,2009,A1 .Location in patent: Page/Page column 13-14

10
[ 796967-16-3 ]
[ 1145835-80-8 ]

Yield	Reaction Conditions	Operation in experiment
> 94%		This process was modified from the current process by adding a cosolvent to reduce the volume of the crystallization process.Currently, the process uses a solution of <strong>[796967-16-3]ABT-869</strong> dissolved in ethanol. This solution is slowly added to water. The current process requires a final volume of 220 ml solvent/g <strong>[796967-16-3]ABT-869</strong>.By adding acetic acid to the ethanol/<strong>[796967-16-3]ABT-869</strong> solution, a more concentrated solution of <strong>[796967-16-3]ABT-869</strong> can be made, reducing the final solvent volume to 60-80 ml solvent/g <strong>[796967-16-3]ABT-869</strong>. Because of equipment constraints, the more concentrated solution of <strong>[796967-16-3]ABT-869</strong> allows for better mixing as well which helps to ensure the desired crystal formation.100 g of <strong>[796967-16-3]ABT-869</strong> was dissolved in a mixture of 590 g ethanol (200 proof) and 771 g of glacial acetic acid. 575 mg of ascorbic acid was added to avoid degradation of the product. The solution was stirred until all the solids dissolve. (If necessary, slight heating (not more than 30° C. for 30 min) can be used to assist dissolution.) The solution was cooled to 25° C.4430 g of water was added to a glass lined jacketed reactor fitted with a retreat curve impeller. (Additional baffling can be used to help mixing efficiency.) The reactor was fitted with an addition tube with an outlet located above the surface of the liquid. The addition tube was situated so liquid will freely fall to the surface of the water (and not drip down the sides of the reactor or the shaft of the impeller). The tip of the addition tube should not be subsurface at any point during the addition. Reactor temperature was maintained at 25° C.+/-5° C.A diaphragm pump or syringe pump was used to slowly add the solution of <strong>[796967-16-3]ABT-869</strong> to the reactor. The solution was added through an inline filter to prevent addition of undissolved solids. The addition was completed at a constant addition rate over the course of not less than two hours. (It is critical that the agitation in the reactor be high (>500 rpm in a 250 ml to be safe) reactor. If the agitation is too low or the rate of addition is too high it is possible to nucleate a different crystal form.)White solid appeared as soon as the <strong>[796967-16-3]ABT-869</strong> solution contacts the water. Through the course of addition, the slurry thickens During the addition, samples can be taken to check the crystal form by x-ray.To ensure desupersaturation, the mixture was stirred for not less than 1 hr. Samples can be taken to ensure the concentration in the liquors is correct.The mixture was filtered through a pot filter fitted with a <10 mum pore size filter cloth (or filter paper). Some breakthrough of the solid occurred initially. After approximately one third of the sample is filtered, the liquors were recirculated to recover any solid that passed through the filter.After filtration, the wetcake was washed with water (three times w/75 ml).Typical yield at the lab scale in this process is >94percent.The solid was dried at 50° C. for NLT 12 hrs.Final water content was <5.0 wt percent. Final acetic acid content was <0.05 wt percent. Crystal form was confirmed by x-ray and DSC.
76%	With water; In ethanol; at 25℃;Product distribution / selectivity;	Following the neutralization with dibasic sodium phosphate, decolorizing carbon treatment and the removal of ethyl acetate as described in EXAMPLE 1, the mixture of <strong>[796967-16-3]ABT-869</strong> in ethanol was gradually mixed with water at 25° C., with vigorous agitation. <strong>[796967-16-3]ABT-869</strong>.H2O Crystalline Form 1 was isolated, washed with water, and dried under reduced pressure while monitoring residual ethyl acetate and ethanol (by GC) and water (by KF). The dried material may be delumped/milled to control particle size. A yield of 76percent is typical.

Reference： [1]Patent: US2009/118344,2009,A1 .Location in patent: Page/Page column 5-6
[2]Patent: US2009/118344,2009,A1 .Location in patent: Page/Page column 5

11
[ 796967-18-5 ]
[ 20925-60-4 ]
[ 796967-16-3 ]

Reference： [1]Organic Process Research and Development,2009,vol. 13,p. 1419 - 1425

12
2-fluoro-5-methyl-phenylisocyanate [ No CAS ]
[ 214360-73-3 ]
[ 796967-16-3 ]

Reference： [1]Chemical Communications,2015,vol. 51,p. 6384 - 6387

13
[ 796967-16-3 ]
[ 111-16-0 ]
7-[3-amino-4-(4-[(2-fluoro-5-methylphenyl)ureido]phenyl)-1H-indazol-1-yl]-7-oxoheptanoic acid [ No CAS ]