[ CAS No. 1227210-37-8 ] {[proInfo.proName]}

Name: 1227210-37-8|6-Fluoro-2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline|97%
Brand: Ambeed
SKU: A389016
Price: 54.0 USD
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Quality Control of [ 1227210-37-8 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 1227210-37-8 ]

SDS Specification

Alternatived Products of [ 1227210-37-8 ]

Product Details of [ 1227210-37-8 ]

CAS No. :	1227210-37-8	MDL No. :	MFCD24040111
Formula :	C₁₃H₁₉BFNO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	RCRQHOCOLMHIIJ-UHFFFAOYSA-N
M.W :	251.10	Pubchem ID :	58540232
Synonyms :

Calculated chemistry of [ 1227210-37-8 ]

Physicochemical Properties

Num. heavy atoms :	18
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.54
Num. rotatable bonds :	1
Num. H-bond acceptors :	3.0
Num. H-bond donors :	1.0
Molar Refractivity :	72.25
TPSA :	44.48 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	Yes
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	Yes
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.92 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	2.69
Log Po/w (WLOGP) :	2.44
Log Po/w (MLOGP) :	1.8
Log Po/w (SILICOS-IT) :	2.02
Consensus Log Po/w :	1.79

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.27
Solubility :	0.134 mg/ml ; 0.000534 mol/l
Class :	Soluble
Log S (Ali) :	-3.28
Solubility :	0.133 mg/ml ; 0.000529 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-4.31
Solubility :	0.0123 mg/ml ; 0.0000491 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	0.0
Synthetic accessibility :	2.92

Safety of [ 1227210-37-8 ]

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 [ 1227210-37-8 ]

* 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 [ 1227210-37-8 ]
Downstream synthetic route of [ 1227210-37-8 ]

[ 1227210-37-8 ] Synthesis Path-Upstream 1~4

1
[ 1227210-36-7 ]
[ 73183-34-3 ]
[ 1227210-37-8 ]

Yield	Reaction Conditions	Operation in experiment
76%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium acetate In 1,4-dioxane for 4.5 h; Inert atmosphere; Reflux	[00226] 3-Bromo-6-fluoro-2-methyl-aniline (500 mg, 2.45 mmol), bis(pinacolato)diboron (747.8 mg, 2.95 mmol) and potassium acetate (721.5 mg, 7.35 mmol) were mixed in 1,4- dioxane (5 mL) and nitrogen gas was bubbled through for 5 minutes. 1,1-bis(diphenyl- phosphino)ferrocene-palladium(ll)dichloride DCM adduct (130 mg, 0.160 mmol) was added andnitrogen bubbled through again. The mixture was heated under reflux conditions for 4.5 hours. TLC (3:2 isohexane/DCM) showed no starting material - LCMS (alyons746-1) showed one main peak R.T 1 .29 minutes, 86percent area, MWt. 252.5 M+H. The reaction was allowed to cool - excess dioxane was removed under vacuum and the residue was partitioned between DCM and Dl water. The mixture was passed through a hydrophobic frit. The DCM phase was reduced downin volume and purified by flash chromatography eluting with 0-100percent ethyl acetate/isohexane over 45 minutes. Concentration of product containing fractions gave 6-fluoro-2-methyl-3- (4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)aniline as an oil which solidified to a white solid overnight SO2mgs, 76percent. [00227] 1 H NMR (DMSO-d6): O 6.86 (m, 2H), 4.76 (bs, 2H), 2.29 (5, 3H), 1 .28 (5, 1 2H).
70%	With potassium acetate In 1,4-dioxane at 100℃; for 6 h; Inert atmosphere	6-fluoro-2-methyl-3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)aniline[00172] A 500-mL round-bottomed flask equipped with a magnetic stirrer, reflux condenser and nitrogen inlet was charged with 1,4-dioxane (140 mL), 3-bromo- 6-fluoro-2-methylaniline (4 g, 19 6 mmol), bis(pinacolato)diboron (6.0 g, 23.5 mmol) and potassium acetate (5.8 g, 58.8 mmol). After bubbling nitrogen through the resulting solution for 30 min, dichloro l,l'-bis(diphenylphosphino) ferrocene palladium (II) dichloromethane adduct (800 mg, 0.98 mmol) was added, and the reaction mixture was heated to 100 ⁰C for 6 h. After this time, the reaction was cooled to room temperature, and water (50 mL) was added. The aqueous layer was extracted with with ethyl acetate (2 x 25 mL). The combined organics were washed with brine (1 x 50 mL), dried with sodium sulfate, absorbed on silica gel and purified by flash chromatography to afford a 70percent yield (3.45 g) of 6-fluoro-2-methyl-3- (4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)aniline.
70%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium acetate In 1,4-dioxane at 100℃; for 6 h; Inert atmosphere	A 500-mL round-bottom flask equipped with a magnetic stirrer, reflux condenser and nitrogen inlet was charged with 1,4-dioxane (140 mL), 3-bromo-6-fluoro-2-methylaniline (S7, 4 g, 19.6 mmol), bis(pinacolato)diboron (6.0 g, 23.5 mmol) and potassium acetate (5.8 g, 58.8 mmol). After bubbling nitrogen through the resulting solution for 30 min, dichloro 1,1’-bis(diphenylphosphino) ferrocene palladium (II) dichloromethane adduct (800 mg, 0.98 mmol) was added, and the reaction mixture was heated to 100 °C for 6 h. Subsequently the reaction was cooled to room temperature before water (50 mL) was added. The aqueous layer was extracted with ethyl acetate (2 x 25 mL). Combined organic layers were washed with brine (1 x 50 mL), dried with sodium sulfate, filtered and concentrated in vacuo. The crude mixture was purified by silica gel flash chromatography using a gradient of 100percent hexanes to 9:1 hexanes:EtOAc to afford 6-fluoro-2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (3.45 g, 70percent yield).

Reference： [1] Patent: WO2015/79251, 2015, A1, . Location in patent: Paragraph 00226; 00227
[2] Patent: WO2010/56875, 2010, A1, . Location in patent: Page/Page column 103-104
[3] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 2, p. 575 - 579

2
[ 1227210-35-6 ]
[ 1227210-37-8 ]

Reference： [1] Patent: WO2015/79251, 2015, A1,

3
[ 3013-27-2 ]
[ 1227210-37-8 ]

Reference： [1] Patent: WO2015/79251, 2015, A1,

4
[ 364-73-8 ]
[ 1227210-37-8 ]

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 2, p. 575 - 579

[ 1227210-37-8 ] Synthesis Path-Downstream 1~21

1
[ 39827-11-7 ]
[ 1227210-37-8 ]
[ 1227210-38-9 ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; In dichloromethane; at 0 - 20℃;Inert atmosphere;	N-(6-fluoro-2-methyl-3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2- yl)phenyl)benzo[b]thiophene-2-carboxamide[00173] A 200-mL single-neck round-bottomed flask equipped with a magnetic stirrer was purged with nitrogen, charged with 6-fluoro-2-methyl-3-(4,4,5,5- tetramethyl-l,3,2-dioxaborolan-2-yl)aniline (3.45 g, 13.7 mmol), methylene chloride (85 mL), and pyridine (3 mL) and cooled to 0 0C. To the resulting solution, benzo[b]thiophene-2-carbonyl chloride (2.7 g, 13.7 mmol) was. The reaction was warmed to room temperature and stirred for 1 h. After this time, aqueous HCl (IM, 50 mL) was added to the reaction. The separated aqueous layer was extracted with dichloromethane (2x 25 mL). The combined organics were washed with aqueous HCl (IM, 2 x 5OmL), water (1 x 5OmL) and brine (50 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting crude white solid (5.6 g, 99% yield) was used in the next step without further purification.
	With pyridine; In dichloromethane; at 0 - 20℃; for 1.0h;Inert atmosphere;	A 200-mL single-neck round-bottom flask equipped with a magnetic stirrer was purged with nitrogen, charged with <strong>[1227210-37-8]6-fluoro-2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline</strong> (S8, 3.45 g, 13.7 mmol), methylene chloride (85 mL), and pyridine (3 mL). After cooling to 0 C, the resulting solution was added with benzo[b]thiophene-2-carbonyl chloride (2.7 g, 13.7 mmol). The reaction mixture was then warmed to room temperature and stirred for 1 h. Subsequently aqueous HCl (1M, 50 mL) was added to the reaction mixture. After separation, the aqueous layer was extracted with dichloromethane (2x 25 mL). Combined organic layers were washed with aqueous HCl (1M, 2 x 50 mL), water (1 x 50 mL) and brine (50 mL), dried with sodium sulfate, filtered and concentrated in vacuo. The resulting crude white solid (5.6 g, 99% yield) was used in the next step without further purification.

Reference： [1]Patent: WO2010/56875,2010,A1 .Location in patent: Page/Page column 104
[2]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 575 - 579

2
[ 1227210-36-7 ]
[ 73183-34-3 ]
[ 1227210-37-8 ]

Yield	Reaction Conditions	Operation in experiment
76%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; for 4.5h;Inert atmosphere; Reflux;	[00226] 3-Bromo-6-fluoro-2-methyl-aniline (500 mg, 2.45 mmol), bis(pinacolato)diboron (747.8 mg, 2.95 mmol) and potassium acetate (721.5 mg, 7.35 mmol) were mixed in 1,4- dioxane (5 mL) and nitrogen gas was bubbled through for 5 minutes. 1,1-bis(diphenyl- phosphino)ferrocene-palladium(ll)dichloride DCM adduct (130 mg, 0.160 mmol) was added andnitrogen bubbled through again. The mixture was heated under reflux conditions for 4.5 hours. TLC (3:2 isohexane/DCM) showed no starting material - LCMS (alyons746-1) showed one main peak R.T 1 .29 minutes, 86% area, MWt. 252.5 M+H. The reaction was allowed to cool - excess dioxane was removed under vacuum and the residue was partitioned between DCM and Dl water. The mixture was passed through a hydrophobic frit. The DCM phase was reduced downin volume and purified by flash chromatography eluting with 0-100% ethyl acetate/isohexane over 45 minutes. Concentration of product containing fractions gave 6-fluoro-2-methyl-3- (4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)aniline as an oil which solidified to a white solid overnight SO2mgs, 76%. [00227] 1 H NMR (DMSO-d6): O 6.86 (m, 2H), 4.76 (bs, 2H), 2.29 (5, 3H), 1 .28 (5, 1 2H).
70%	With potassium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; at 100℃; for 6.0h;Inert atmosphere;	6-fluoro-2-methyl-3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)aniline[00172] A 500-mL round-bottomed flask equipped with a magnetic stirrer, reflux condenser and nitrogen inlet was charged with 1,4-dioxane (140 mL), 3-bromo- 6-fluoro-2-methylaniline (4 g, 19 6 mmol), bis(pinacolato)diboron (6.0 g, 23.5 mmol) and potassium acetate (5.8 g, 58.8 mmol). After bubbling nitrogen through the resulting solution for 30 min, dichloro l,l'-bis(diphenylphosphino) ferrocene palladium (II) dichloromethane adduct (800 mg, 0.98 mmol) was added, and the reaction mixture was heated to 100 0C for 6 h. After this time, the reaction was cooled to room temperature, and water (50 mL) was added. The aqueous layer was extracted with with ethyl acetate (2 x 25 mL). The combined organics were washed with brine (1 x 50 mL), dried with sodium sulfate, absorbed on silica gel and purified by flash chromatography to afford a 70% yield (3.45 g) of 6-fluoro-2-methyl-3- (4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)aniline.
70%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 100℃; for 6.0h;Inert atmosphere;	A 500-mL round-bottom flask equipped with a magnetic stirrer, reflux condenser and nitrogen inlet was charged with 1,4-dioxane (140 mL), 3-bromo-6-fluoro-2-methylaniline (S7, 4 g, 19.6 mmol), bis(pinacolato)diboron (6.0 g, 23.5 mmol) and potassium acetate (5.8 g, 58.8 mmol). After bubbling nitrogen through the resulting solution for 30 min, dichloro 1,1?-bis(diphenylphosphino) ferrocene palladium (II) dichloromethane adduct (800 mg, 0.98 mmol) was added, and the reaction mixture was heated to 100 C for 6 h. Subsequently the reaction was cooled to room temperature before water (50 mL) was added. The aqueous layer was extracted with ethyl acetate (2 x 25 mL). Combined organic layers were washed with brine (1 x 50 mL), dried with sodium sulfate, filtered and concentrated in vacuo. The crude mixture was purified by silica gel flash chromatography using a gradient of 100% hexanes to 9:1 hexanes:EtOAc to afford 6-fluoro-2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (3.45 g, 70% yield).

Reference： [1]Patent: WO2015/79251,2015,A1 .Location in patent: Paragraph 00226; 00227
[2]Patent: WO2010/56875,2010,A1 .Location in patent: Page/Page column 103-104
[3]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 575 - 579

3
[ 1227210-35-6 ]
[ 1227210-37-8 ]