1060808-92-5|6-Bromo-4-chloronicotinic acid| Ambeed

Size	Price	VIP Price	US Stock	Global Stock	In Stock
{[ item.pr_size ]}		Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}

US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days

{[ item.pr_size ]}

In Stock

- +

Please Login or Create an Account to: See VIP prices and availability

US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks

Quality Control of [ 1060808-92-5 ] Purity: 97% SDS Specification

COA

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

NMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

CNMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

HPLC

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

LC-MS

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

1-2 Day Shipping
High Quality
Technical Support

Product Details of [ 1060808-92-5 ]

CAS No. :	1060808-92-5
Formula :	C₆H₃BrClNO₂
M.W :	236.45
SMILES Code :	O=C(O)C1=CN=C(Br)C=C1Cl
MDL No. :	MFCD13189219
InChI Key :	XWVFYJPQFMTKCQ-UHFFFAOYSA-N
Pubchem ID :	72212216

Safety of [ 1060808-92-5 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Computational Chemistry of [ 1060808-92-5 ] Show Less

Physicochemical Properties

Num. heavy atoms	11
Num. arom. heavy atoms	6
Fraction Csp3	0.0
Num. rotatable bonds	1
Num. H-bond acceptors	3.0
Num. H-bond donors	1.0
Molar Refractivity	43.91
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	50.19 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.36
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	2.03
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.2
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	0.25
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	2.08
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.58

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.92
Solubility	0.283 mg/ml ; 0.0012 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-2.71
Solubility	0.459 mg/ml ; 0.00194 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-2.87
Solubility	0.316 mg/ml ; 0.00134 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	Yes
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	No
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-6.3 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	0.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.56

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	1.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	1.7

Application In Synthesis of [ 1060808-92-5 ]

* 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.

Downstream synthetic route of [ 1060808-92-5 ]

[ 1060808-92-5 ] Synthesis Path-Downstream 1~35

1
[ 1544241-64-6 ]
[ 1060808-92-5 ]
[ 1609545-93-8 ]

Yield	Reaction Conditions	Operation in experiment
37.6%	With triethylamine; In dichloromethane; at 0 - 20℃; for 1h;	[00251j Step 4: (R)-4-Amino-3-fluoro-2-methylbutan-2-ol (2.82 g, 23.26 mmol) inDCM (25 mL) was added TEA (8.84 mL, 63.4 mmol) at 0 C. The acid chloride prepared above was dissolved in DCM (75 mL) and added dropwise at 0 C to the amine solution. The reaction mixture was stirred for 30 mm and allowed to warm to room temperature for 30 mm. The reaction mixture was diluted with DCM (150 mL) and washed with water and brine. The organic layer was dried over Na2504, filtered and concentrated to give(R)-6-bromo-4-chloro-N-(2-fluoro-3 -hydroxy-3 -methylbutyl)nicotinamide (2.7 g, 7.95mmol, 37.6% yield) as a brown oil. The residue was purified via columnchromatography (pet ether:EA, 15-20%). ?H NMR (400 MHz, DMSO-d6) oe 8.90 (t, J=5.6 Hz, 1H), 8.47 (s, 1H), 7.91 (s, 1H), 4.84 (s, 1H), 4.31 (ddd, J= 49.6, 8.4, 2.0 Hz, 1H),3.77 (ddd, J= 38.4, 14.8, 6.0 Hz, 1H), 3.69 (m, 1H), 1.17 (s, sH), 1.15 (s, 3H).

References: [1]Patent: WO2014/74675,2014,A1 .Location in patent: Paragraph 00251.

2
6-chloro-4-bromo-5-(trimethylsilyl)nicotinic acid [ No CAS ]
[ 1060808-92-5 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In methanol; at 20℃; for 2h;	[00194j Step 2: To solution of 6-chloro-4-bromo-5-(trimethylsilyl)nicotinic acid (4 g,13 mmol) in MeOH (100 mL) and was added K2C03 (4 g, 29 mmol). The reactionmixture was stirred at rt for 2 h. The reaction mixture was slowly added to ice thenacidified with 10% H2504. The aqueous layer was extracted twice with EtOAc (50 mL).The separated organic layer was dried (Na2504) and concentrated to afford the crude0product 6-chloro-4-bromonicotinic acid (2.3 g, 75/0 yield). LCMS m/z 233.9 (M) ; HNMR (400 MHz, DMSO-d6) oe 14.05 (br s, 1H), 8.77 (s, 1H), 8.06 (s, 1H).

References: [1]Patent: WO2014/74657,2014,A1 .Location in patent: Paragraph 00194.

3
[ 1060808-92-5 ]
[ 1610017-91-8 ]

References: [1]Patent: WO2014/74657,2014,A1 .

4
[ 1060808-92-5 ]
[ 1609546-60-2 ]

Yield	Reaction Conditions	Operation in experiment
	With oxalyl dichloride; In dichloromethane; at 0 - 50℃; for 1h;	Br[00195j Step 3: A suspension of <strong>[1060808-92-5]6-bromo-4-chloronicotinic acid</strong> (5 g, 21.15 mmol) inDCM (75 mL) was cooled to 0 C. Oxalyl chloride (3.70 ml, 42.3 mmol) was added and 20 the reaction mixture was heated at 50 C for 1 h. The reaction mixture was cooled to rtand the excess oxalyl chloride and DCM was removed by distillation to obtain the acid chloride as a brown oil which was used directly in the next step.
	With oxalyl dichloride; In dichloromethane; at 0 - 50℃; for 1h;Heating;	[00250j Step 3: A suspension of <strong>[1060808-92-5]6-bromo-4-chloronicotinic acid</strong> (5 g, 21.15 mmol) in DCM (75 mL) was cooled to 0 C. Oxalyl chloride (3.70 ml, 42.3 mmol) was added and the reaction mixture was heated at 50 C for 1 h. The reaction mixture was cooled toroom temperature and the excess oxalyl chloride and DCM was removed by distillation to obtain the acid chloride as a brown oil which was used directly in the next step.

References: [1]Patent: WO2014/74657,2014,A1 .Location in patent: Paragraph 00195.
[2]Patent: WO2014/74675,2014,A1 .Location in patent: Paragraph 00250.

5
[ 1060808-92-5 ]
[ 1609545-93-8 ]

References: [1]Patent: WO2014/74657,2014,A1 .

6
[ 1060808-92-5 ]
[ 1610021-14-1 ]

References: [1]Patent: WO2014/74657,2014,A1 .

7
[ 1060808-92-5 ]
4-chloro-6-(3-fluoro-5-isobutoxy-phenyl)-N-[(6-nitro-2-pyridyl)sulfonyl]pyridine-3-carboxamide [ No CAS ]

References: [1]Patent: US2016/95858,2016,A1 .

8
[ 1060808-92-5 ]
N-[(6-amino-2-pyridyl)sulfonyl]-4-chloro-6-(3-fluoro-5-isobutoxy-phenyl)pyridine-3-carboxamide [ No CAS ]

References: [1]Patent: US2016/95858,2016,A1 .

9
[ 1060808-92-5 ]
N-[(6-amino-2-pyridyl)sulfonyl]-6-(3-fluoro-5-isobutoxy-phenyl)-4-[(4S)-2,2,4-trimethylpyrrolidin-1-yl]pyridine-3-carboxamide [ No CAS ]

References: [1]Patent: US2016/95858,2016,A1 .

10
[ 1060808-92-5 ]
(3-fluoro-5-isobutoxy-phenyl)boronic acid [ No CAS ]
4-chloro-6-(3-fluoro-5-isobutoxy-phenyl)pyridine-3-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; at 80℃; for 10h;Inert atmosphere;	To 6-bromo-4-chloro-pyridine-3-carboxylic acid (205 mg, 0.865 mmol), (3-fluoro-5-isobutoxy-phenyl)boronic acid (184 mg, 0.865 mmol), and palladium;triphenylphosphane (30.0 mg, 0.0260 mmol) in dioxane (4 mL) was added solution of potassium carbonate (1.73 mL of 2 M, 3.46 mmol) under an atmosphere of nitrogen and the reaction mixture was stirred at 80 C. for 10 h. The reaction mixture was concentrated under reduced pressure, partitioned between water (15 mL) and EtOAc (15 mL). The aqueous layer was acidified with HCl and washed with EtOAc (3×15 mL). The combined organic layers was washed with brine (1×25 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The solid obtained was washed with hexanes to give 4-chloro-6-(3-fluoro-5-isobutoxy-phenyl)pyridine-3-carboxylic acid (232 mg, 83%) as a tan solid. ESI-MS m/z calc. 323.07245. found 324.1 (M+1)+. Retention time: 0.74 minutes.

References: [1]Patent: US2016/95858,2016,A1 .Location in patent: Paragraph 5609; 5610.

11
methyl 6-bromo-4-chloropyridine-3-carboxylate [ No CAS ]
[ 1060808-92-5 ]

Yield	Reaction Conditions	Operation in experiment
	With lithium hydroxide; In methanol; water; at 43℃;	To a solution of methyl 6-bromo-4-chloronicotinate (15 g, 59.89 mmol) in methanol (240 mL) was added lithium hydroxide (2.93 g, 119.77 mmol) in water (68 mL). The solution was heated to 43 C. overnight and subsequently cooled to room temperature. Aqueous hydrochloric acid (1M, 120 mL) was added and volatiles were removed in vacuo. The resulting slurry was filtered and washed with H2O to provide 6-bromo-4-chloronicotinic acid. ES/MS: 237.967 (M+H+). 1H NMR (400 MHz, DMSO-d6) delta 8.75 (s, 1H), 8.03 (s, 1H).
	With water; lithium hydroxide; In methanol; at 43℃;	To a solution of methyl 6-bromo-4-chloronicotinate (15 g, 59.89 mmol) in methanol (240 mL) was added lithium hydroxide (2.93 g, 119.77 mmol) in water (68 mL). The solution was heated to 43 C. overnight and subsequently cooled to room temperature. Aqueous hydrochloric acid (1M, 120 mL) was added and volatiles were removed in vacuo. The resulting slurry was filtered and washed with H2O to provide 6-bromo-4-chloronicotinic acid. ES/MS: 238.0 (M+H+). 1H NMR (400 MHz, DMSO-d6) delta 8.75 (s, 1H), 8.03 (s, 1H).

References: [1]Patent: US2018/230157,2018,A1 .Location in patent: Paragraph 0283-0286.
[2]Patent: US2020/17510,2020,A1 .Location in patent: Paragraph 0096; 0105-0107.

12
[ 1060808-92-5 ]
(R)-4-chloro-6-(3-cyanopyrrolo[1,2-b]pyridazin-7-yl)-N-(2-fluoro-3-hydroxy-3-methylbutyl)nicotinamide [ No CAS ]

References: [1]Patent: US2018/230157,2018,A1 .
[2]Patent: US2020/17510,2020,A1 .

13
[ 1060808-92-5 ]
(R)-6-bromo-4-((6-chloropyridin-3-yl)amino)-N-(2-fluoro-3-hydroxy-3-methylbutyl)nicotinamide [ No CAS ]

References: [1]Patent: US2018/230157,2018,A1 .

14
[ 1060808-92-5 ]
(R)-4-((6-chloropyridin-3-yl)amino)-6-(3-cyanopyrrolo[1,2-b]pyridazin-7-yl)-N-(2-fluoro-3-hydroxy-3-methylbutyl)nicotinamide trifluoroacetate [ No CAS ]

References: [1]Patent: US2018/230157,2018,A1 .

15
[ 1060808-92-5 ]
(R)-4-amino-3-fluoro-2-methylbutan-2-ol hydrochloride [ No CAS ]
[ 1609545-93-8 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20℃;	To a solution of <strong>[1060808-92-5]6-bromo-4-chloronicotinic acid</strong> (3 g, 12.69 mmol) in DMF (42 mL) was added HATU (6.27 g, 16.49 mmol), (R)-4-amino-3-fluoro-2-methylbutan-2-ol hydrochloride (2.4 g, 15.23 mmol), and N,N-Diisopropylethylamine (5.62 ml, 32.26 mmol). The resulting solution was stirred at room temperature overnight and subsequently diluted with ethyl acetate. The organic solution was washed with saturated aqueous lithium chloride (3 times), then dried over Na2SO4, and the concentrated. The residue was purified by silica gel chromatography (eluent: EtOAc/hexanes) to provide (R)-6-bromo-4-chloro-N-(2-fluoro-3-hydroxy-3-methylbutyl)nicotinamide. ES/MS: 341.089 (M+H+). 1H NMR (400 MHz, DMSO-d6) delta 8.88 (t, J=5.5 Hz, 1H), 8.41 (s, 1H), 8.01 (s, 1H), 4.82 (s, 1H), 4.28 (ddd, J=49.3, 9.4, 2.0 Hz, 1H), 3.84-3.63 (m, 1H), 3.40-3.22 (m, 1H), 1.13 (d, J=7.0 Hz, 6H).
	With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20℃;	To a solution of <strong>[1060808-92-5]6-bromo-4-chloronicotinic acid</strong> (3 g, 12.69 mmol) in DMF (42 mL) was added HATU (6.27 g, 16.49 mmol), (R)-4-amino-3-fluoro-2-methylbutan-2-ol hydrochloride (2.4 g, 15.23 mmol), and N,N-Diisopropylethylamine (5.62 ml, 32.26 mmol). The resulting solution was stirred at room temperature overnight and subsequently diluted with ethyl acetate. The organic solution was washed with saturated aqueous lithium chloride (3 times), then dried over Na2SO4, and then concentrated. The residue was purified by silica gel chromatography (eluent: EtOAc/hexanes) to provide (R)-6-bromo-4-chloro-N-(2-fluoro-3-hydroxy-3-methylbutyl)nicotinamide. ES/MS: 341.1 (M+H+). 1H NMR (400 MHz, DMSO-d6) delta 8.88 (t, J=5.5 Hz, 1H), 8.41 (s, 1H), 8.01 (s, 1H), 4.82 (s, 1H), 4.28 (ddd, J=49.3, 9.4, 2.0 Hz, 1H), 3.84-3.63 (m, 1H), 3.40-3.22 (m, 1H), 1.13 (d, J=7.0 Hz, 6H).

References: [1]Patent: US2018/230157,2018,A1 .Location in patent: Paragraph 0283; 0287-0289.
[2]Patent: US2020/17510,2020,A1 .Location in patent: Paragraph 0096; 0108-0110.

16
[ 1060808-92-5 ]
methyl 6-bromo-4-[2-methoxy-4-(trifluoromethoxy)phenoxy]pyridine-3-carboxylate [ No CAS ]