[ CAS No. 194804-91-6 ] {[proInfo.proName]}

Name: 194804-91-6|4-Bromo-2,3-difluorobenzoic acid|96%
Brand: Ambeed
SKU: A613318
Price: 7.0 USD
Availability: InStock
Rating: 91 (27 reviews)

,{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]}

DV 2D 3D

3d Animation Molecule Structure of 194804-91-6

Structure of 194804-91-6 * Storage: {[proInfo.prStorage]}

Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

For Research Only 110K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 194804-91-6 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 194804-91-6 ]

SDS Specification

Alternatived Products of [ 194804-91-6 ]

Product Details of [ 194804-91-6 ]

CAS No. :	194804-91-6	MDL No. :	MFCD07368121
Formula :	C₇H₃BrF₂O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	IRUDFVTZXQTEFN-UHFFFAOYSA-N
M.W :	237.00	Pubchem ID :	19358360
Synonyms :

Calculated chemistry of [ 194804-91-6 ]

Physicochemical Properties

Num. heavy atoms :	12
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	4.0
Num. H-bond donors :	1.0
Molar Refractivity :	41.02
TPSA :	37.3 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) :	-6.08 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.48
Log Po/w (XLOGP3) :	2.34
Log Po/w (WLOGP) :	3.27
Log Po/w (MLOGP) :	3.21
Log Po/w (SILICOS-IT) :	2.75
Consensus Log Po/w :	2.61

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	0.0
Bioavailability Score :	0.56

Water Solubility

Log S (ESOL) :	-3.09
Solubility :	0.194 mg/ml ; 0.000817 mol/l
Class :	Soluble
Log S (Ali) :	-2.76
Solubility :	0.409 mg/ml ; 0.00173 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.19
Solubility :	0.153 mg/ml ; 0.000647 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.48

Safety of [ 194804-91-6 ]

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 [ 194804-91-6 ]

* 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.

Downstream synthetic route of [ 194804-91-6 ]

[ 194804-91-6 ] Synthesis Path-Downstream 1~88

1
[ 194804-91-6 ]
[ 162744-55-0 ]

Yield	Reaction Conditions	Operation in experiment
100%		Step 1: (4-bromo-2,3-difluorophenyl)methanolA solution of <strong>[194804-91-6]4-bromo-2,3-difluorobenzoic acid</strong> (2.0 g, 8.4 mmol, Alfa) in dry THF (25 mL) added BH3 (29.2mL, 1 mol/L in THF) at rt under nitrogen atmosphere. The reaction mixture was stirred at rt overnight. The reaction mixture was cooled down to 0 C and quenched whit aq. HCI (2N, 20 mL) and extracted with EtOAc (50 mL x 3). The combined organic layers were washed with 10% NaHC03 (100 mL), water (100 mL) and brine (100 mL) and then, dried over anhydrous Na2S04. After the removal of solvent to afford (4-bromo-2,3- difluorophenyl)methanol (.1.91 g, quantitative) as a yellow solid. 1H NMR (300MHz, CDCI3) 5= 7.34 - 7.29 (m, 1 H), 7.15 - 7.09 (m, 1 H), 4.75 (s, 2H), 1.90 (brs, 1 H).
63.8%		To a solution of <strong>[194804-91-6]4-bromo-2,3-difluorobenzoic acid</strong> (650 mg, 2.74 mmol) in THF (5 mL) stirred under N2 at 0 C. was added BH3.DMS (1.371 mL, 13.71 mmol) in one charge. The reaction mixture was stirred at 67 C. for 2 h. To the solution was added MeOH (5 mL) at rt. Then the solution was stirred at rt for 30 min. The solution was concentrated in vacuo to give the crude product. The resulting (4-bromo-2,3-difluorophenyl)methanol (600 mg, 1.749 mmol, 63.8% yield) was used in the next step without further purification. TLC (PE/EA=2:1, Rf 0.6): 1H NMR (400 mHz, CDCl3) delta 7.37-7.28 (m, 1H), 7.12 (t, J=7.4 Hz, 1H), 4.76 (d, J=5.2 Hz, 2H), 3.70 (s, 1H).
	With dimethylsulfide borane complex; In tetrahydrofuran; at 0 - 67℃; for 2h;Inert atmosphere;	To a solution of <strong>[194804-91-6]4-bromo-2,3-difluorobenzoic acid</strong> (650 mg, 2.74 mmol) in THF (5 mL) stirred under N2 at 0 C was added BH3 DMS (1.371 mL, 13.71 mmol) in one charge. The reaction mixture was stirred at 67 C for 2 h. To the solution was added MeOH (5 mL) at rt. Then the solution was stirred at rt for 30 min. The solution was concentrated in vacuo to give the crude product. The resulting (4-bromo-2,3-difluorophenyl)methanol (600 mg, 1.749 mmol, 63.8% yield) was used in the next step without further purification. TLC (PE/EA = 2: 1, Rf 0.6): NMR (400 mHz, CDC13) delta 7.37-7.28 (m, 1H), 7.12 (t, J= 7.4 Hz, 1H), 4.76 (d, J = 5.2 Hz, 2H), 3.70 (s, 1H).

Reference： [1]Patent: WO2012/67664,2012,A1 .Location in patent: Page/Page column 47
[2]Patent: US2014/275111,2014,A1 .Location in patent: Paragraph 0319; 0320
[3]Patent: WO2014/141187,2014,A1 .Location in patent: Page/Page column 69

2
[ 194804-91-6 ]
[ 162744-56-1 ]

Reference： [1]Patent: WO2012/67664,2012,A1
[2]Patent: US2014/275111,2014,A1
[3]Patent: WO2014/141187,2014,A1

3
[ 194804-91-6 ]
[ 1378869-11-4 ]

Reference： [1]Patent: WO2012/67664,2012,A1

4
[ 194804-91-6 ]
[ 1378868-42-8 ]

Reference： [1]Patent: WO2012/67664,2012,A1

5
[ 194804-91-6 ]
[ 1378869-12-5 ]

Reference： [1]Patent: WO2012/67664,2012,A1

6
[ 194804-91-6 ]
[ 1378868-43-9 ]

Reference： [1]Patent: WO2012/67664,2012,A1

7
[ 194804-91-6 ]
[ 1378869-19-2 ]

Reference： [1]Patent: WO2012/67664,2012,A1

8
[ 194804-91-6 ]
[ 1378868-45-1 ]

Reference： [1]Patent: WO2012/67664,2012,A1

9
[ 194804-91-6 ]
[ 1447017-99-3 ]

Reference： [1]Chinese Chemical Letters,2013,vol. 24,p. 673 - 676

10
[ 194804-91-6 ]
[ 1349717-52-7 ]

Yield	Reaction Conditions	Operation in experiment
100%	With thionyl chloride; for 2h;Reflux;	General procedure: A mixture of various carboxylic acids (1.0mmol), an excess of thionyl chrolide (5mL) was refluxed for 2h and concentrated in vacuo to give corresponding acyl chloride (quant).
1.08 g	With oxalyl dichloride; N,N-dimethyl-formamide; In dichloromethane; at 20℃; for 2h;	To <strong>[194804-91-6]4-bromo-2,3-difluoro-benzoic acid</strong> (1.0 g, 4.22 mmol) in DCM (50 mL) was added oxalyl chloride (0.54 mL, 6.33 mmol) followed by catalytic DMF (1 drop). The mixture was stirred 2 h at room temperature and then evaporated to dryness to afford the acid chloride (1.08 g, 4.22 mmol) which was then redissolved in THF (10 mL). Separately, ethyl isocyanoacetate (0.51 mL, 4.64 mmol) in THF (10 mL) was cooled to 0C and Et3N (1.75 mL, 12.65 mmol) was added dropwise followed by the addition of 4-bromo-2,3-difluoro-benzoyl chloride (1.08 g, 4.22 mmol) in THF (10 mL) over 5 min. The reaction mixture was allowed to warm to room temperature and stirred overnight. The mixture was then evaporated to near dryness and diluted with DCM (10 mL). This was followed by consecutive washes of saturated aq. NaHCC (3 x 20 mL) and brine (20 mL). The DCM layer was then dried over Na2SC>4 and concentrated in vacuo to give a dark red oil. The crude oil was then purified by column chromatography using an eluent system of 0-40% petroleum ether (40-60) in EtOAc to give 5-(4-bromo-2,3-difluoro-phenyl)oxazole-4-carboxylate (1.2 g, 86 %) as a yellow oil. LC-MS (Method A) 332.3/334.3 [M+H]+; RT 3.04 min

Reference： [1]Chinese Chemical Letters,2013,vol. 24,p. 673 - 676
[2]ACS Medicinal Chemistry Letters,2016,vol. 7,p. 198 - 203
[3]Patent: WO2017/46605,2017,A1 .Location in patent: Page/Page column 68-69

11
[ 194804-91-6 ]
2-(4-bromo-2,3-difluorophenyl)acetonitrile [ No CAS ]

Reference： [1]Patent: US2014/275111,2014,A1
[2]Patent: WO2014/141187,2014,A1

12
[ 194804-91-6 ]
2-(4-bromo-2,3-difluorophenyl)acetic acid [ No CAS ]

Reference： [1]Patent: US2014/275111,2014,A1
[2]Patent: WO2014/141187,2014,A1

13
[ 194804-91-6 ]
N-(4-(2-(benzyloxy)ethoxy)-3-(trifluoromethyl)phenyl)-2-(4-bromo-2,3-difluorophenyl)acetamide [ No CAS ]

Reference： [1]Patent: US2014/275111,2014,A1
[2]Patent: WO2014/141187,2014,A1

14
[ 194804-91-6 ]
N-(4-(2-(benzyloxy)ethoxy)-3-(trifluoromethyl)phenyl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2,3-difluorophenyl)acetamide [ No CAS ]

Reference： [1]Patent: US2014/275111,2014,A1
[2]Patent: WO2014/141187,2014,A1

15
[ 194804-91-6 ]
2-(4-(5-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2,3-difluorophenyl)-N-(4-(2-hydroxyethoxy)-3-(trifluoromethyl)phenyl)acetamide [ No CAS ]

Reference： [1]Patent: US2014/275111,2014,A1
[2]Patent: WO2014/141187,2014,A1

16
[ 194804-91-6 ]
C₁₁H₁₀F₂O₂ [ No CAS ]

Reference： [1]Patent: WO2015/144799,2015,A1
[2]Patent: WO2015/144801,2015,A1

17
[ 194804-91-6 ]
C₁₁H₁₂F₂O₂ [ No CAS ]

Reference： [1]Patent: WO2015/144799,2015,A1

18
[ 194804-91-6 ]
C₂₂H₂₇BF₂O₃ [ No CAS ]

Reference： [1]Patent: WO2015/144799,2015,A1
[2]Patent: WO2015/144801,2015,A1
[3]Patent: WO2015/144801,2015,A1

19
[ 194804-91-6 ]
C₃₅H₄₂F₂N₄O₃Si [ No CAS ]

Reference： [1]Patent: WO2015/144799,2015,A1

20
[ 194804-91-6 ]
C₂₉H₂₈F₂N₄O₃ [ No CAS ]

Reference： [1]Patent: WO2015/144799,2015,A1

21
[ 194804-91-6 ]
C₃₃H₃₄F₂N₄O₄ [ No CAS ]

Reference： [1]Patent: WO2015/144799,2015,A1

22
[ 194804-91-6 ]
C₃₀H₃₀F₂N₄O₄ [ No CAS ]

Reference： [1]Patent: WO2015/144799,2015,A1

23
[ 194804-91-6 ]
C₃₃H₃₄F₂N₄O₄ [ No CAS ]

Reference： [1]Patent: WO2015/144799,2015,A1

24
[ 194804-91-6 ]
C₃₀H₃₀F₂N₄O₄ [ No CAS ]

Reference： [1]Patent: WO2015/144799,2015,A1

25
[ 67-56-1 ]
[ 194804-91-6 ]
methyl 4-bromo-2,3-difluorobenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%	With sulfuric acid; at 50℃; for 72h;	a- Synthesis of Int. 220: H2S04 (1.1 mL, 21 mmol) was slowly added to a sol. of <strong>[194804-91-6]4-bromo-2,3-difluorobenzoic acid</strong> (2.5 g, 10.5 mmol) in MeOH (40 mL). The mixture was heated at 50C for 3 days. The mixture was concentrated in vacuo and the residue was partitioned between EtOAc and water and basified with K2C03. The combined organic layers were washed with brine, dried (MgS04), filtered and concentrated in vacuo to give 2.6 g of Int. 220, colorless oil which crystallized in white solid 98%).
98%	With sulfuric acid; at 50℃; for 72h;	a- Synthesis of intermediate 23:H2504 (1.1 mL, 21 mmol) was slowly added to a solution of <strong>[194804-91-6]4-bromo-2,3-difluorobenzoic acid</strong> (2.5 g, 10.5 mmol) in MeOH (40 mL). The mixture was heated at50C for 3 days. The mixture was concentrated in vacuo and the residue waspartitioned between EtOAc and water and basified with K2C03. The combined organic layers were washed with brine, dried over Mg504, filtered and concentrated in vacuo to give 2.6 g of intermediate 23, colorless oil which crystallized in a white solid (98%).
98%	With sulfuric acid; at 0℃;Inert atmosphere; Reflux;	Cone. H2SO4 (1 10 mL) was added drop wise using addition funnel to a solution of 4-bromo- 2,3-difluoro benzoic acid (1 10 g) in (550 mL) of methanol at 0 C under nitrogen. The reaction mixture was stirred at reflux temperature for overnight. The reaction mixture was quenched with cold water and extracted with EtOAc. The organic layer was washed with saturated NaHC03 solution, dried over sodium sulfate and concentrated to afford white solid as the desired product (1 15 g, 98 % yield). The product was used in the next step without further purification. 1H NMR (400 MHz, DMSO) delta 7.74 - 7.63 (m, 2H), 3.89 (s, 3H).

Reference： [1]Patent: WO2015/144799,2015,A1 .Location in patent: Page/Page column 202
[2]Patent: WO2015/144801,2015,A1 .Location in patent: Page/Page column 84
[3]Patent: WO2016/20836,2016,A1 .Location in patent: Page/Page column 170; 171
[4]Bioconjugate Chemistry,2019

26
[ 194804-91-6 ]
C₁₀H₁₀F₂O [ No CAS ]

Reference： [1]Patent: WO2015/144801,2015,A1

27
[ 194804-91-6 ]
C₁₀H₁₂F₂O [ No CAS ]

Reference： [1]Patent: WO2015/144801,2015,A1
[2]Patent: WO2015/144801,2015,A1

28
[ 194804-91-6 ]
C₂₆H₂₄F₂N₄O [ No CAS ]

Reference： [1]Patent: WO2015/144801,2015,A1
[2]Patent: WO2015/144801,2015,A1

29
[ 194804-91-6 ]
C₂₄H₂₀F₅N₇O [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2016,vol. 7,p. 198 - 203

30
[ 194804-91-6 ]
C₃₂H₂₆F₅N₇O₃ [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2016,vol. 7,p. 198 - 203

31
[ 194804-91-6 ]
C₁₉H₁₈BF₅N₂O₃ [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2016,vol. 7,p. 198 - 203

32
[ 194804-91-6 ]
C₁₃H₆BrF₅N₂O [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2016,vol. 7,p. 198 - 203

33
[ 194804-91-6 ]
(R)-4-(8-amino-3-(1-(3-methyloxetane-3-carbonyl)piperidin-3-yl)imidazo[1,5-a]pyrazin-1-yl)-2,3-difluoro-N-(4-(trifluoromethyl)pyridin-2-yl)benzamide [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2016,vol. 7,p. 198 - 203

34
[ 194804-91-6 ]
(S)-4-(aminomethyl)-7-(3-aminopyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-8-methylquinolin-2(1H)-one trifluoroacetate [ No CAS ]