[ CAS No. 1266322-58-0 ] {[proInfo.proName]}

Name: 1266322-58-0|7-Bromoquinolin-3-amine|98%
Brand: Ambeed
SKU: A545857
Price: 39.0 USD
Availability: InStock
Rating: 98 (35 reviews)

,{[proInfo.pro_purity]}

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

2D 3D

Structure of 1266322-58-0 * 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 [ 1266322-58-0 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 1266322-58-0 ]

SDS Specification

Alternatived Products of [ 1266322-58-0 ]

Product Details of [ 1266322-58-0 ]

CAS No. :	1266322-58-0	MDL No. :	MFCD20258866
Formula :	C₉H₇BrN₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	CCHYPYCCQBLGLJ-UHFFFAOYSA-N
M.W :	223.07	Pubchem ID :	52554379
Synonyms :

Calculated chemistry of [ 1266322-58-0 ]

Physicochemical Properties

Num. heavy atoms :	12
Num. arom. heavy atoms :	10
Fraction Csp3 :	0.0
Num. rotatable bonds :	0
Num. H-bond acceptors :	1.0
Num. H-bond donors :	1.0
Molar Refractivity :	53.85
TPSA :	38.91 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.01 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.72
Log Po/w (XLOGP3) :	2.32
Log Po/w (WLOGP) :	2.59
Log Po/w (MLOGP) :	1.9
Log Po/w (SILICOS-IT) :	2.4
Consensus Log Po/w :	2.19

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.3
Solubility :	0.111 mg/ml ; 0.0005 mol/l
Class :	Soluble
Log S (Ali) :	-2.78
Solubility :	0.374 mg/ml ; 0.00168 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-4.2
Solubility :	0.014 mg/ml ; 0.000063 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.65

Safety of [ 1266322-58-0 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P280	UN#:	N/A
Hazard Statements:	H315	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 1266322-58-0 ]

* 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 [ 1266322-58-0 ]
Downstream synthetic route of [ 1266322-58-0 ]

[ 1266322-58-0 ] Synthesis Path-Upstream 1~2

1
[ 1375108-38-5 ]
[ 1266322-58-0 ]

Yield	Reaction Conditions	Operation in experiment
97%	With hydrazine hydrate In ethanol for 1 h; Reflux	A suspension of intermediate 396 ( 14 g, 38.5 mmol) in ethanol ( 1 50 mL) was treated with NH₂ H₂.H₂O (4.5 g, 76.9 mmol ) and was re fluxed for l hour. The mixture was al lowed to cool and filtered. The filtrate was col lected and evaporated to obtain intermediate 397 (8.6 g, 94percent yield).
56%	With hydrazine In ethanol for 1 h; Reflux	A suspension of 2-(7-bromoquinolin-3-yl)isoindoline-l,3-dione (10 g, 28.3 mmol) in ethanol (200 mL) was treated with hydrazine (1.777 mL, 56.6 mmol) then heated under reflux for 1 h. The mixture was allowed to cool, the precipitate was collected and washed with a little ethanol, and the filtrate was evaporated to a grey solid. The isolated solid was dissolved in warm ethanol and adsorbed onto silica gel. Purification of the solid by silica gel chromatography (50-100percent) ethyl acetate/hexanes) afforded the title compound (3.5 g, 56percent). 1H NMR (400 MHz, DMSO-d6) δ ppm 5.83 (s, 2 H) 7.14 (d, J=2.53 Hz, 1 H) 7.49 (dd, J=8.84, 2.02 Hz, 1 H) 7.54 - 7.65 (m, 1 H) 7.94 (d, J=1.77 Hz, 1 H) 8.46 (d, J=2.78 Hz, 1 H).
56%	With hydrazine In ethanol for 1 h; Reflux	A suspension of 2-(7-bromoquinolin-3-yl)isoindoline-1 ,3-dione (10 g, 28.3 mmol) in ethanol (200 mL) was treated with hydrazine (1.777 mL, 56.6 mmol) then heated under reflux for 1 h. The mixture was allowed to cool, the precipitate was collected and washed with a little ethanol, and the filtrate was evaporated to a grey solid. The isolated solid was dissolved in warm ethanol and adsorbed onto silica gel. Purification of thesolid by silica gel chromatography (50-100percent ethyl acetate/hexanes) afforded the title compound (3.5 g, 56percent). 1H NMR (400 MHz, DMSO-d6) δ ppm 5.83 (s, 2H) 7.14 (d, J=2.53 Hz, 1H) 7.49 (dd, J=8.84, 2.02 Hz, 1H) 7.54 - 7.65 (m, 1H) 7.94 (d, J=1 .77 Hz, 1H) 8.46 (d, J=2.78 Hz, 1H).

56%	With hydrazine In ethanol for 1 h; Reflux	b) 7-bromoquinolin-3-amineA suspension of 2-(7-bromoquinolin-3 -yl)isoindoline- 1,3 -dione (10 g, 28.3 mmol) in ethanol (200 mL) was treated with hydrazine (1.777 mL, 56.6 mmol) then heated under reflux for 1 h. The mixture was allowed to cool, the precipitate was collected and washed with a little ethanol, and the filtrate was evaporated to a grey solid. The isolated solid wasdissolved in warm ethanol and adsorbed onto silica gel. Purification by silica gel chromatography (50-100percent ethyl acetate/hexanes) afforded the title compound (3.5 g, 5 6percent). ‘H NMR (400 MHz, DMSO-d6) 0 ppm 5.83 (s, 2 H) 7.14 (d, J=2.53 Hz, 1 H) 7.49 (dd, J8.84, 2.02 Hz, 1 H) 7.54 - 7.65 (m, 1 H) 7.94 (d, J1.77 Hz, 1 H) 8.46 (d, J=2.78 Hz, 1 H).
56%	With hydrazine In ethanol for 1 h; Reflux	A suspension of 2-(7-bromoquinolin-3-yl)isoindoline-l,3-dione (10 g, 28.3 mmol) in ethanol (200 mL) was treated with hydrazine (1.777 mL, 56.6 mmol) then heated under reflux for 1 h. The mixture was allowed to cool, the precipitate was collected and washed with a little ethanol, and the filtrate was evaporated to a grey solid. The isolated solid was dissolved in warm ethanol and adsorbed onto silica gel. Purification by silica gel chromatography (50-100percent ethyl acetate/hexanes) afforded the title compound (3.5 g, 56percent>). 1H NMR (400 MHz, DMSO-d₆) δ ppm 5.83 (s, 2 H) 7.14 (d, J=2.53 Hz, 1 H) 7.49 (dd, J=8.84, 2.02 Hz, 1 H) 7.54 - 7.65 (m, 1 H) 7.94 (d, J=1.77 Hz, 1 H) 8.46 (d, J=2.78 Hz, 1 H).
56%	With hydrazine In ethanol for 1 h; Reflux	A suspension of 2-(7-bromoquinolin-3-yl)isoindoline-1 ,3-dione (10 g, 28.3 mmol) in ethanol (200 mL) was treated with hydrazine (1.777 mL, 56.6 mmol) then heated under reflux for 1 h. The mixture was allowed to cool, the precipitate was collected and washed with a little ethanol, and the filtrate was evaporated to a grey solid. The isolated solid was dissolved in warm ethanol and adsorbed onto silica gel. Purification of the solid by silica gel chromatography (50-100percent ethyl acetate/hexanes) afforded the title compound (3.5 g, 56percent). ¹H NMR (400MHz, DMSO-d6) δ ppm 5.83 (s, 2 H) 7.14 (d, J=2.53 Hz, 1 H) 7.49 (dd, J=8.84, 2.02 Hz, 1 H) 7.54 - 7.65 (m, 1 H) 7.94 (d, J=1.77 Hz, 1 H) 8.46 (d, J=2.78 Hz, 1 H).

Reference： [1] Patent: WO2017/32840, 2017, A1, . Location in patent: Page/Page column 265; 266
[2] Patent: WO2013/28447, 2013, A1, . Location in patent: Page/Page column 117
[3] Patent: WO2013/52716, 2013, A1, . Location in patent: Page/Page column 63
[4] Patent: WO2013/177253, 2013, A2, . Location in patent: Page/Page column 64
[5] Patent: WO2014/8223, 2014, A2, . Location in patent: Page/Page column 71-72
[6] Patent: WO2014/108858, 2014, A1, . Location in patent: Page/Page column 39

2
[ 59278-65-8 ]
[ 1266322-58-0 ]

Reference： [1] Patent: WO2013/177253, 2013, A2,
[2] Patent: WO2014/8223, 2014, A2,
[3] Patent: WO2014/108858, 2014, A1,
[4] Patent: WO2013/28447, 2013, A1,
[5] Patent: WO2013/52716, 2013, A1,

[ 1266322-58-0 ] Synthesis Path-Downstream 1~28

1
[ 1375108-38-5 ]
[ 1266322-58-0 ]

Yield	Reaction Conditions	Operation in experiment
97%	With hydrazine hydrate; In ethanol; for 1h;Reflux;	A suspension of intermediate 396 ( 14 g, 38.5 mmol) in ethanol ( 1 50 mL) was treated with NH2 H2.H2O (4.5 g, 76.9 mmol ) and was re fluxed for l hour. The mixture was al lowed to cool and filtered. The filtrate was col lected and evaporated to obtain intermediate 397 (8.6 g, 94% yield).
56%	With hydrazine; In ethanol; for 1h;Reflux;	A suspension of 2-(7-bromoquinolin-3-yl)isoindoline-l,3-dione (10 g, 28.3 mmol) in ethanol (200 mL) was treated with hydrazine (1.777 mL, 56.6 mmol) then heated under reflux for 1 h. The mixture was allowed to cool, the precipitate was collected and washed with a little ethanol, and the filtrate was evaporated to a grey solid. The isolated solid was dissolved in warm ethanol and adsorbed onto silica gel. Purification of the solid by silica gel chromatography (50-100%) ethyl acetate/hexanes) afforded the title compound (3.5 g, 56%). 1H NMR (400 MHz, DMSO-d6) delta ppm 5.83 (s, 2 H) 7.14 (d, J=2.53 Hz, 1 H) 7.49 (dd, J=8.84, 2.02 Hz, 1 H) 7.54 - 7.65 (m, 1 H) 7.94 (d, J=1.77 Hz, 1 H) 8.46 (d, J=2.78 Hz, 1 H).
56%	With hydrazine; In ethanol; for 1h;Reflux;	A suspension of 2-(7-bromoquinolin-3-yl)isoindoline-1 ,3-dione (10 g, 28.3 mmol) in ethanol (200 mL) was treated with hydrazine (1.777 mL, 56.6 mmol) then heated under reflux for 1 h. The mixture was allowed to cool, the precipitate was collected and washed with a little ethanol, and the filtrate was evaporated to a grey solid. The isolated solid was dissolved in warm ethanol and adsorbed onto silica gel. Purification of thesolid by silica gel chromatography (50-100% ethyl acetate/hexanes) afforded the title compound (3.5 g, 56%). 1H NMR (400 MHz, DMSO-d6) delta ppm 5.83 (s, 2H) 7.14 (d, J=2.53 Hz, 1H) 7.49 (dd, J=8.84, 2.02 Hz, 1H) 7.54 - 7.65 (m, 1H) 7.94 (d, J=1 .77 Hz, 1H) 8.46 (d, J=2.78 Hz, 1H).

56%	With hydrazine; In ethanol; for 1h;Reflux;	b) 7-bromoquinolin-3-amineA suspension of 2-(7-bromoquinolin-3 -yl)isoindoline- 1,3 -dione (10 g, 28.3 mmol) in ethanol (200 mL) was treated with hydrazine (1.777 mL, 56.6 mmol) then heated under reflux for 1 h. The mixture was allowed to cool, the precipitate was collected and washed with a little ethanol, and the filtrate was evaporated to a grey solid. The isolated solid wasdissolved in warm ethanol and adsorbed onto silica gel. Purification by silica gel chromatography (50-100% ethyl acetate/hexanes) afforded the title compound (3.5 g, 5 6%). ?H NMR (400 MHz, DMSO-d6) 0 ppm 5.83 (s, 2 H) 7.14 (d, J=2.53 Hz, 1 H) 7.49 (dd, J8.84, 2.02 Hz, 1 H) 7.54 - 7.65 (m, 1 H) 7.94 (d, J1.77 Hz, 1 H) 8.46 (d, J=2.78 Hz, 1 H).
56%	With hydrazine; In ethanol; for 1h;Reflux;	A suspension of 2-(7-bromoquinolin-3-yl)isoindoline-l,3-dione (10 g, 28.3 mmol) in ethanol (200 mL) was treated with hydrazine (1.777 mL, 56.6 mmol) then heated under reflux for 1 h. The mixture was allowed to cool, the precipitate was collected and washed with a little ethanol, and the filtrate was evaporated to a grey solid. The isolated solid was dissolved in warm ethanol and adsorbed onto silica gel. Purification by silica gel chromatography (50-100% ethyl acetate/hexanes) afforded the title compound (3.5 g, 56%>). 1H NMR (400 MHz, DMSO-d6) delta ppm 5.83 (s, 2 H) 7.14 (d, J=2.53 Hz, 1 H) 7.49 (dd, J=8.84, 2.02 Hz, 1 H) 7.54 - 7.65 (m, 1 H) 7.94 (d, J=1.77 Hz, 1 H) 8.46 (d, J=2.78 Hz, 1 H).
56%	With hydrazine; In ethanol; for 1h;Reflux;	A suspension of 2-(7-bromoquinolin-3-yl)isoindoline-1 ,3-dione (10 g, 28.3 mmol) in ethanol (200 mL) was treated with hydrazine (1.777 mL, 56.6 mmol) then heated under reflux for 1 h. The mixture was allowed to cool, the precipitate was collected and washed with a little ethanol, and the filtrate was evaporated to a grey solid. The isolated solid was dissolved in warm ethanol and adsorbed onto silica gel. Purification of the solid by silica gel chromatography (50-100% ethyl acetate/hexanes) afforded the title compound (3.5 g, 56%). 1H NMR (400MHz, DMSO-d6) delta ppm 5.83 (s, 2 H) 7.14 (d, J=2.53 Hz, 1 H) 7.49 (dd, J=8.84, 2.02 Hz, 1 H) 7.54 - 7.65 (m, 1 H) 7.94 (d, J=1.77 Hz, 1 H) 8.46 (d, J=2.78 Hz, 1 H).
	With hydrazine; In ethanol; at 100℃; for 16h;	To a mixture of 2- (7-bromoquinolin-3-yl) isoindoline-1, 3-dione (100 mg, 0.283 mmol) and hydrazine (1.0 mL, 31.9 mmol) was charged ethanol (15 mL) , and the reaction mixture was stirred at 100 for 16 hours. The reaction mixture was cooled to room temperature and concentrated in vacuo. Purification by column chromatography over silica gel, eluting with petroleum ether /ethyl acetate, afforded the title compound. LC/MS = 223 [M+1] .1H-NMR (CDCl3, 400 MHz) delta 8.48 (d, J = 2.4 Hz, 1H) , 8.11 (s, 1H) , 7.49 (dd, J = 1.6, 8.8 Hz, 1H) , 7.45 (d, J = 8.8 Hz, 1H) , 7.19 (d, J = 2.4 Hz, 1H) , 3.93 (br s, 2H) .

Reference： [1]Patent: WO2017/32840,2017,A1 .Location in patent: Page/Page column 265; 266
[2]Patent: WO2013/28447,2013,A1 .Location in patent: Page/Page column 117
[3]Patent: WO2013/52716,2013,A1 .Location in patent: Page/Page column 63
[4]Patent: WO2013/177253,2013,A2 .Location in patent: Page/Page column 64
[5]Patent: WO2014/8223,2014,A2 .Location in patent: Page/Page column 71-72
[6]Patent: WO2014/108858,2014,A1 .Location in patent: Page/Page column 39
[7]Patent: WO2020/87202,2020,A1 .Location in patent: Page/Page column 48

2
[ 1266322-58-0 ]
(+)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(3-fluoroquinolin-7-yl)phenyl)acetamide [ No CAS ]
(-)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(3-fluoroquinolin-7-yl)phenyl)acetamide [ No CAS ]

Reference： [1]Patent: WO2013/28447,2013,A1

3
[ 1266322-58-0 ]
[ 1375108-29-4 ]

Yield	Reaction Conditions	Operation in experiment
36%	With tert.-butylnitrite; boron trifluoride dihydrate; In chlorobenzene; at 50 - 100℃; for 2h;Inert atmosphere;	To a 100 mL round bottom flask containing a solution of <strong>[1266322-58-0]7-bromoquinolin-3-amine</strong> (2.00 g, 8.97 mmol) in chlorobenzene (20 mL) was added borontrifluoride dihydrate (0.900 mL, 13.6 mmol) dropwise via a syringe. The solution was stirred under nitrogen as the flask temperature was raised to 50 C. Terf-butyl nitrite (1.185 mL, 8.97 mmol) was added slowly dropwise (over 15 min) to the reaction mixture via an addition funnel. The flask temperature was raised to 100 C and the reaction mixture was stirred under nitrogen for 2 h. The reaction mixture was cooled to room temperature and then poured into a flask containing ice and saturated aq sodium bicarbonate (-100 mL). The reaction flask was washed with chloroform and dichloromethane and the organic washes (-100 mL) were transferred to a separatory funnel along with the aqueous layer. The organic layer was removed and the aqueous layer was washed with chloroform (3x). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. Purification of the residue by silica gel chromatography (20-50% dichloromethane: hexanes) afforded the title compound (731 mg, 36%). MS(ES)+ m/e 227.9 [M+H]+.
35%		A solution of <strong>[1266322-58-0]7-bromoquinolin-3-amine</strong> (1.0 g, 4.48 mmol) in chlorobenzene (10 mL) was added dropwise over 10 min onto boron trif uoride dihydrate (0.429 mL, 6.72 mmol). The mixture was heated to 50 C and t-butyl nitrite (0.773 mL, 4.48 mmol) was added at this temperature over 20 min. The temperature was then raised to 100 C and the mixture was stirred for 30 min. The reaction mixture was cooled and poured onto ice/aqueous sodium bicarbonate solution. The resulting solid was suspended in ethanol, diluted with additional aqueous sodium bicarbonate solution, and extracted with chloroform (x3). The combined extracts were washed with dilute brine, dried (sodium sulfate) and evaporated under reduced pressure. Purification of the residue by silica gel chromatography (100% dichloromethane) afforded the title compound (350 mg, 35%). 1H NMR (400 MHz, DMSO- 6) 5ppm 7.84 (dd, J=8.72, 1.39 Hz, 1 H) 8.00 (d, J=8.84 Hz, 1 H) 8.31 (d, J=2.02 Hz, 1 H) 8.34 (dd, J=9.47, 2.91 Hz, H) 9.00 (d, 1 H).
35%	With tert.-butylnitrite; boron trifluoride dihydrate; In chlorobenzene; at 50 - 100℃; for 0.833333h;	A solution of <strong>[1266322-58-0]7-bromoquinolin-3-amine</strong> (1.0 g, 4.48 mmol) in chlorobenzene (10 mL) was added dropwise over 10 mm onto boron trifluoride dihydrate (0.429 mL, 6.72 mmol). The mixture was heated to 50 C and t-butyl nitrite (0.773 mL, 4.48 mmol) was added at this temperature over 20 min. The temperature was then raised to 100 C and the mixture was stirred for 30 min. The reaction mixture was cooled and poured onto ice/aqueous sodium bicarbonate solution. The resulting solid was suspended in ethanol, diluted with additional aqueous sodium bicarbonate solution, and extracted with chloroform (x3). The combined extracts were washed with dilute brine, dried (sodiumsulfate) and evaporated under reduced pressure. Purification of the residue by silica gelchromatography (100% dichloromethane) afforded the title compound (350 mg, 35%). 1H NMR (400 MHz, DMSO-d6) delta ppm 7.84 (dd, J=8.72, 1.39 Hz, 1H) 8.00 (d, J=8.84 Hz,1H) 8.31 (d, J=2.02 Hz, 1H) 8.34 (dd, J=9.47, 2.91 Hz, H) 9.00 (d, 1H).

35%	With tert.-butylnitrite; boron trifluoride dihydrate; In chlorobenzene; at 50 - 100℃; for 0.833333h;	A solution of <strong>[1266322-58-0]7-bromoquinolin-3-amine</strong> (1.0 g, 4.48 mmol) in chlorobenzene (10 mL) was added dropwise over 10 minutes onto boron trifluoride dihydrate (0.429 mL, 6.72 mmol). The mixture was heated to 50 C and t-butyl nitrite (0.773 mL, 4.48 mmol) was added at this temperature over 20 minutes. The temperature was then raised to 100 C and the mixture was stirred for 30 minutes. The reaction mixture was cooled and poured onto ice/aqueous sodium bicarbonate solution. The resulting solid was suspended in ethanol, diluted with additional aqueous sodium bicarbonate solution, and extracted with chloroform (x3). The combined extracts were washed with dilute brine, dried (anhyd. sodium sulfate) and evaporated under reduced pressure. Purification by silica gel chromatography (100% dichloromethane) afforded the title compound (350 mg, 35%). 1H NMR (400 MHz, DMSO- d6) 5ppm 7.84 (dd, J=8.72, 1.39 Hz, 1 H) 8.00 (d, J=8.84 Hz, 1 H) 8.31 (d, J=2.02 Hz, 1 H) 8.34 (dd, J=9.47, 2.91 Hz, H) 9.00 (d, 1 H).
19%	With tert.-butylnitrite; boron trifluoride diethyl etherate; In chlorobenzene; at 60 - 100℃; for 1h;	Intermediate 397 (8 g, 35.86 mmol ) was dissolved in PhCl (80 mL ). Boron tri fluoride diethyl etherate (4.45 mL ) was added drop-wise over 10 mins. The mixture was heated to 60 C. Tert-butyl nitrite (6. 1 mL) was added drop-wise over 20 mins at this temperature. The reaction solution was heated to 100 C and stirred for 1 hour. The mixture was cooled and poured into an ice/aqueous sodium bicarbonate solut ion. The mixture was extracted with CH2CI2 (500 mL x 2 ). The combined organic layers were washed with brine, dried ( a2S04) and concentrated by vacuum to give the crude product. The crude product was purified by column chromatography (gradient eluent: petroleum ether/ ethyl acetate from 1 / 0 to 20/ 1 ) to obtain intermediate 398 ( 1 .57 g, 19% yield).
	With boron trifluoride dihydrate; sodium nitrite; at 100℃; for 16h;	To <strong>[1266322-58-0]7-bromoquinolin-3-amine</strong> (50 mg, 0.224 mmol) was charged boron trifluoride dihydrate (0.5 mL, 7.88 mmol) , followed by sodium nitrite (17.0 mg, 0.247 mmol) . The reaction mixture was stirred at 100 for 16 hours. It was cooled to room temperature, and saturated aqueous sodium carbonate was added until pH reached 10. The aqueous layer was extracted with ethyl acetate (20 mL) , and the combined organic extracts were dried (magnesium sulfate) , filtered, and concentrated in vacuo to afford the crude product. Purification by column chromatography over silica gel, eluting with petroleum ether /tetrahydrofuran, gave the purified fractions. LC/MS = 226 [M+1] .1H-NMR (CDCl3, 400 MHz) delta 8.96 (d, J = 2.4 Hz, 1H) , 8.30 (dd, J = 2.4, 9.2 Hz, 1H) , 8.27 (s, 1H) , 7.95 (d, J = 8.4 Hz, 1H) , 7.80 (d, J = 8.4 Hz, 1H

Reference： [1]Patent: WO2014/108858,2014,A1 .Location in patent: Page/Page column 39
[2]Patent: WO2013/28447,2013,A1 .Location in patent: Paragraph 117-118
[3]Patent: WO2013/52716,2013,A1 .Location in patent: Page/Page column 64
[4]Patent: WO2014/8223,2014,A2 .Location in patent: Page/Page column 78-79
[5]Patent: WO2017/32840,2017,A1 .Location in patent: Page/Page column 266
[6]Patent: WO2020/87202,2020,A1 .Location in patent: Page/Page column 49

4
[ 1266322-58-0 ]
[ 1429790-68-0 ]

Reference： [1]Patent: WO2013/52716,2013,A1

5
[ 59278-65-8 ]
[ 1266322-58-0 ]

Reference： [1]Patent: WO2013/177253,2013,A2
[2]Patent: WO2014/8223,2014,A2
[3]Patent: WO2014/108858,2014,A1
[4]Patent: WO2013/28447,2013,A1
[5]Patent: WO2013/52716,2013,A1

6
[ 1266322-58-0 ]
[ 75-36-5 ]
N-(7-bromoquinolin-3-yl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 2h;Cooling with ice;	c) N-(7-bromoquinolin-3 -yl)acetamideA solution of <strong>[1266322-58-0]7-bromoquinolin-3-amine</strong> (300 mg, 1.345 mmol) and N-ethyl-N-isopropylpropan-2-amine (0.35 1 mL, 2.0 17 mmol) in dichloromethane (10 mL) was cooled in an ice bath and treated with acetyl chloride (0.105 mL, 1.479 mmol). The reaction was stirred at ambient temperature for 2 h. Some starting amine remained, though the reactionhad stopped progressing. The mixture was washed with aq. sodium bicarbonate solution andapplied to a silica gel header column (20 g). Purification by silica gel chromatography (100%dichloromethane then 5% methanol/dichloromethane) afforded the title compound (215 mg,60%) as a white solid. ?H NMR (400 MHz, DMSO-d6) 0 ppm 2.15 (s, 3 H) 7.70 (dd, J=8.59,2.02 Hz, 1 H) 7.93 (d, J=8.84 Hz, 1 H) 8.15 (d, J=2.02 Hz, 1 H) 8.74 (d, J2.27 Hz, 1 H)8.90 (d, J=2.53 Hz, 1 H) 10.50 (s, 1 H).
60%	With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 2h;	A solution of 7-bromoquinolin-3 -amine (300 mg, 1.345 mmol) and N-ethyl-N- isopropylpropan-2-amine (0.351 mL, 2.017 mmol) in dichloromethane (10 mL) was cooled in an ice bath and treated with acetyl chloride (0.105 mL, 1.479 mmol). The reaction was stirred at ambient temperature for 2 h. Some starting amine remained, though the reaction had stopped progressing. The mixture was washed with aq. sodium bicarbonate solution and applied to a silica gel header column (20 g). Purification by silica gel chromatography (100% dichloromethane then 5% methanol/dichloromethane) afforded the title compound (215 mg, 60%) as a white solid. 1H NMR (400 MHz, DMSO-d6) delta ppm 2.15 (s, 3 H) 7.70 (dd, J=8.59, 2.02 Hz, 1 H) 7.93 (d, J=8.84 Hz, 1 H) 8.15 (d, J=2.02 Hz, 1 H) 8.74 (d, J=2.27 Hz, 1 H) 8.90 (d, J=2.53 Hz, 1 H) 10.50 (s, 1 H). d

Reference： [1]Patent: WO2013/177253,2013,A2 .Location in patent: Page/Page column 64
[2]Patent: WO2014/8223,2014,A2 .Location in patent: Page/Page column 72

7
[ 1266322-58-0 ]
[ 1534371-32-8 ]

Reference： [1]Patent: WO2014/8223,2014,A2

8
[ 1266322-58-0 ]
[ 124-63-0 ]
[ 1375108-45-4 ]

Yield	Reaction Conditions	Operation in experiment
46%	With pyridine; In acetonitrile; at 20 - 50℃; for 45h;	A solution of 7-bromoquinolin-3 -amine (300 mg, 1.345 mmol) and pyridine (0.109 mL, 1.345 mmol) in acetonitrile (20 mL) was treated with methanesulfonyl chloride (0.104 mL, 1.345 mmol) and stirred at ambient temperature for 1 h. The reaction was proceeding slowly, therefore, it was heated to 40 C and stirred for 20 h. LCMS showed 50-60% conversion so the temperature was raised to 50 C and the mixture was stirred for a further 24 h. The reaction was evaporated under reduced pressure. Purification by flash chromatography (0- 5% methanol in dichloromethane) afforded the title compound (186 mg, 46%). 1H NMR (400 MHz, DMSO- 6) 5ppm 3.16 (s, 3 H) 7.74 (dd, J=8.84, 2.02 Hz, 1 H) 7.96 (d, J=8.84 Hz, 1 H) 8.13 (d, J=2.78 Hz, 1 H) 8.19 (d, J=2.02 Hz, 1 H) 8.76 (d, J=2.78 Hz, 1 H) 10.40 (s, 1 H)

Reference： [1]Patent: WO2014/8223,2014,A2 .Location in patent: Page/Page column 76

9
[ 1266322-58-0 ]
[ 1619968-86-3 ]

Reference： [1]Patent: WO2014/108858,2014,A1

10
[ 1266322-58-0 ]
5-(2-(benzylthio)-6-bromophenyl)-1H-tetrazole [ No CAS ]
[ 824-94-2 ]
C₄₀H₃₇N₇O₅S [ No CAS ]
C₄₀H₃₇N₇O₅S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		An isomeric mixture of 3-(5,5-dimethyl-l,3,2-dioxaborinan-2-yl)-N,N-bis(4- methoxybenzyl)-2-(l-(4-methoxybenzyl)-lH-tetrazol-5-yl)benzenesulfonamide and 3-(5,5- dimethyl- 1 ,3 ,2-dioxaborinan-2-yl)-N,N-bis(4-methoxybenzyl)-2-(2-(4-methoxybenzyl)-2H- tetrazol-5-yl)benzenesulfonamide, Reference Example 9, (80 mg, 0.12 mmol), were combined with commercially available or known aryl or heteroaryl bromides (0.138 mmol), cesium carbonate (1 12 mg, 0.344 mmol) and 2nd Generation Xphos Precatalyst (13.5 mg, 17 muiotaetaomicron) in a 1 dram vial and taken into the glove box. Dioxane (0.8 mL) and water (0.2 mL) were added and the mixture stirred at 85C for 18 hours. Then 2 mL DCM and 1 mL saturated ammonium chloride was added and the mixtures were stirred for 5 minutes. The aqeuous layer was removed by pipette and the remaning organics concentrated under reduced pressure in the genevac.
		General procedure: Step C: 5-(2-(Benzylthio)-6-bromophenyl)-1-(4-methoxybenzyl)-1H-tetrazole and 5-(2-(benzylthio)-6-bromophenyl)-2-(4-methoxybenzyl)-1H-tetrazole (0291) To a solution of 5-(2-(benzylthio)-6-bromophenyl)-1H-tetrazole in a mixture of chloroform and water (6 mL and 8 mL, respectively) were added potassium carbonate (1.544 g, 11.17 mmol), tetrabutylammonium chloride (0.311 g, 1.12 mmol) followed by a solution of 1-(chloromethyl)-4-methoxybenzene (1.14 mL, 8.38 mmol) in 2 mL of CHCl3 at 15 C. The resulting mixture was slowly warm to rt, and heated at 50 C. for 3 hr. The reaction mixture was cooled to rt, and transferred to a sep. funnel. The organic layer was separated, dried over MgSO4, filtered and purified using 5 to 80% ethyl acetate in hexanes to provide a mixture of 5-(2-(benzylthio)-6-bromophenyl)-1-(4-methoxybenzyl)-1H-tetrazole and 5-(2-(benzylthio)-6-bromophenyl)-2-(4-methoxybenzyl)-1H-tetrazole. Step D: 3-Bromo-2-(1-(4-methoxybenzyl)-1H-tetrazol-5-yl)benzenesulfonamide and 3-bromo-2-(2-(4-methoxybenzyl)-1H-tetrazol-5-yl)benzenesulfonamide (0292) To a solution of the mixture of 5-(2-(benzylthio)-6-bromophenyl)-1-(4-methoxybenzyl)-1H-tetrazole and 5-(2-(benzylthio)-6-bromophenyl)-2-(4-methoxybenzyl)-1H-tetrazole in DCM (40 mL) was added water (0.251 mL, 13.9 mmol) followed by acetic acid (0.796 ml, 13.91 mmol). The resulting mixture was cooled to 0 C., then a solution of sulfuryl chloride (1.131 mL, 13.91 mmol) in DCM (2 mL) was slowly added. The reaction mixture was slowly warmed to rt, and stirred for 4 hr, and then evaporated to dryness. To this residue was added THF (5 mL) and then a mixture of aqueous ammonium hydroxide and THF (20 mL each) at 0 C. The reaction mixture was slowly warmed to rt and stirred for 1.5 hr. The resulting solution was diluted with ethyl acetate (100 mL), washed with water (50 mL) and brine (50 mL). The organic layer was dried over MgSO4, filtered and purified by column chromatography on silica gel eluted with 10 to 90% ethyl acetate in hexanes to provide mixture of 3-bromo-2-(1-(4-methoxybenzyl)-1H-tetrazol-5-yl)benzenesulfonamide and 3-bromo-2-(2-(4-methoxybenzyl)-1H-tetrazol-5-yl)benzenesulfonamide. Reference Example 8 3-bromo-N,N-bis(4-methoxybenzyl)-2-(1-(4-methoxybenzyl)-1H-tetrazol-5-yl)benzenesulfonamide and 3-bromo-N,N-bis(4-methoxybenzyl)-2-(2-(4-methoxybenzyl)-2H-tetrazol-5-yl)benzenesulfonamide (0308) (0309) To a mixture of 3-Bromo-2-(1-(4-methoxybenzyl)(1H-tetrazol-5-yl))benzenesulfonamide and 3-bromo-2-(2-(4-methoxybenzyl)(1H-tetrazol-5-yl))benzenesulfonamide isomers (3.00 g, 7.07 mmol), 1-(chloromethyl)-4-methoxybenzene (2.436 g, 15.56 mmol), in butanone at room temperature, was added potassium carbonate (3.91 g, 28.3 mmol) and sodium iodide (2.332 g, 15.56 mmol). The reaction mixture was stirred overnight under N2 at 80 C. LC-MS showed completion of the reaction. The reaction was filtered and the cake was washed with EtOAc. The filtrates were evaporated, and the crude product was purified by column chromatography (EtOAc/hexanes 0-100%) to afford the title compounds. LC/MS [M+H]+: 664, 666. Reference Example 9 3-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-N,N-bis(4-methoxybenzyl)-2-(1-(4-methoxybenzyl)-1H-tetrazol-5-yl)benzenesulfonamide and 3-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-N,N-bis(4-methoxybenzyl)-2-(2-(4-methoxybenzyl)-2H-tetrazol-5-yl)benzenesulfonamide (0310) (0311) To a reaction vessel was added an isomeric mixture of 3-bromo-N,N-bis(4-methoxybenzyl)-2-(1-(4-methoxybenzyl)-1H-tetrazol-5-yl)benzenesulfonamide and 3-bromo-N,N-bis(4-methoxybenzyl)-2-(2-(4-methoxybenzyl)-2H-tetrazol-5-yl)benzenesulfonamide (3.23 g, 4.86 mmol), 5,5,5?,5?-tetramethyl-2,2?-bi(1,3,2-dioxaborinane) (3.29 g, 14.6 mmol), PCy3 Pd G2 (0.287 g, 0.486 mmol), and potassium acetate (1.431 g, 14.58 mmol). Then anhydrous acetonitrile (new bottle, 25 mL) was added to this flask. Nitrogen was bubbled through this mixture for 10 min, then the mixture was heated at 85 C. for 24 hr. The mixture was cooled to room temperature. 1 M NaOH was added to the reaction mixture. The mixture was extracted with EtOAc. The organic phase was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with 0-80% hexane/EtOAc to give the product, which was contaminated by about of de-Br side product.Step A: Palladium Catalyzed C-C Coupling of Arylboronic Ester with Bromides (0866) An isomeric mixture of 3-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-N,N-bis(4-methoxybenzyl)-2-(1-(4-methoxybenzyl)-1H-tetrazol-5-yl)benzenesulfonamide and 3-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-N,N-bis(4-methoxybenzyl)-2-(2-(4-methoxybenzyl)-2H-tetrazol-5-yl)benzenesulfonamide, Reference Example 9, (80 mg, 0.12 mmol), were combined with commercially available or known aryl or heteroaryl bromides (0.138 mmol), cesium carbonate (112 mg, 0.344 mmol) and 2nd Generation Xphos Precatalyst (13.5 mg, 17 mumol) in a 1 dram vial and taken into the glove box. Dioxane (0.8 mL) a...

Reference： [1]Patent: WO2015/112441,2015,A1 .Location in patent: Page/Page column 261; 262
[2]Patent: US2016/333021,2016,A1 .Location in patent: Paragraph 0291; 0292; 0309; 0311; 0866

11
[ 1266322-58-0 ]
5-(2-(benzylthio)-6-bromophenyl)-1H-tetrazole [ No CAS ]
3-(3-amino-7-quinolyl)-2-(1H-tetrazol-5-yl)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		To each vial from Step A was added Anisole (0.125 ml, 1.15 mmol) and TFA (1 mL) and the mixture stirred at 60C for 4 hours. The mixture was allowed to cool and the volatile organics removed in the genevac. DMSO (1 mL) was added and the mixtures were filtered through a 96 well 0.4 micron filter plate. These crude materials and others made in the same way were purified by mass directed reverse phase HPLC to afford Examples 416-419.
		General procedure: Step C: 5-(2-(Benzylthio)-6-bromophenyl)-1-(4-methoxybenzyl)-1H-tetrazole and 5-(2-(benzylthio)-6-bromophenyl)-2-(4-methoxybenzyl)-1H-tetrazole (0291) To a solution of 5-(2-(benzylthio)-6-bromophenyl)-1H-tetrazole in a mixture of chloroform and water (6 mL and 8 mL, respectively) were added potassium carbonate (1.544 g, 11.17 mmol), tetrabutylammonium chloride (0.311 g, 1.12 mmol) followed by a solution of 1-(chloromethyl)-4-methoxybenzene (1.14 mL, 8.38 mmol) in 2 mL of CHCl3 at 15 C. The resulting mixture was slowly warm to rt, and heated at 50 C. for 3 hr. The reaction mixture was cooled to rt, and transferred to a sep. funnel. The organic layer was separated, dried over MgSO4, filtered and purified using 5 to 80% ethyl acetate in hexanes to provide a mixture of 5-(2-(benzylthio)-6-bromophenyl)-1-(4-methoxybenzyl)-1H-tetrazole and 5-(2-(benzylthio)-6-bromophenyl)-2-(4-methoxybenzyl)-1H-tetrazole. Step D: 3-Bromo-2-(1-(4-methoxybenzyl)-1H-tetrazol-5-yl)benzenesulfonamide and 3-bromo-2-(2-(4-methoxybenzyl)-1H-tetrazol-5-yl)benzenesulfonamide (0292) To a solution of the mixture of 5-(2-(benzylthio)-6-bromophenyl)-1-(4-methoxybenzyl)-1H-tetrazole and 5-(2-(benzylthio)-6-bromophenyl)-2-(4-methoxybenzyl)-1H-tetrazole in DCM (40 mL) was added water (0.251 mL, 13.9 mmol) followed by acetic acid (0.796 ml, 13.91 mmol). The resulting mixture was cooled to 0 C., then a solution of sulfuryl chloride (1.131 mL, 13.91 mmol) in DCM (2 mL) was slowly added. The reaction mixture was slowly warmed to rt, and stirred for 4 hr, and then evaporated to dryness. To this residue was added THF (5 mL) and then a mixture of aqueous ammonium hydroxide and THF (20 mL each) at 0 C. The reaction mixture was slowly warmed to rt and stirred for 1.5 hr. The resulting solution was diluted with ethyl acetate (100 mL), washed with water (50 mL) and brine (50 mL). The organic layer was dried over MgSO4, filtered and purified by column chromatography on silica gel eluted with 10 to 90% ethyl acetate in hexanes to provide mixture of 3-bromo-2-(1-(4-methoxybenzyl)-1H-tetrazol-5-yl)benzenesulfonamide and 3-bromo-2-(2-(4-methoxybenzyl)-1H-tetrazol-5-yl)benzenesulfonamide. Reference Example 8 3-bromo-N,N-bis(4-methoxybenzyl)-2-(1-(4-methoxybenzyl)-1H-tetrazol-5-yl)benzenesulfonamide and 3-bromo-N,N-bis(4-methoxybenzyl)-2-(2-(4-methoxybenzyl)-2H-tetrazol-5-yl)benzenesulfonamide (0308) (0309) To a mixture of 3-Bromo-2-(1-(4-methoxybenzyl)(1H-tetrazol-5-yl))benzenesulfonamide and 3-bromo-2-(2-(4-methoxybenzyl)(1H-tetrazol-5-yl))benzenesulfonamide isomers (3.00 g, 7.07 mmol), 1-(chloromethyl)-4-methoxybenzene (2.436 g, 15.56 mmol), in butanone at room temperature, was added potassium carbonate (3.91 g, 28.3 mmol) and sodium iodide (2.332 g, 15.56 mmol). The reaction mixture was stirred overnight under N2 at 80 C. LC-MS showed completion of the reaction. The reaction was filtered and the cake was washed with EtOAc. The filtrates were evaporated, and the crude product was purified by column chromatography (EtOAc/hexanes 0-100%) to afford the title compounds. LC/MS [M+H]+: 664, 666. Reference Example 9 3-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-N,N-bis(4-methoxybenzyl)-2-(1-(4-methoxybenzyl)-1H-tetrazol-5-yl)benzenesulfonamide and 3-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-N,N-bis(4-methoxybenzyl)-2-(2-(4-methoxybenzyl)-2H-tetrazol-5-yl)benzenesulfonamide (0310) (0311) To a reaction vessel was added an isomeric mixture of 3-bromo-N,N-bis(4-methoxybenzyl)-2-(1-(4-methoxybenzyl)-1H-tetrazol-5-yl)benzenesulfonamide and 3-bromo-N,N-bis(4-methoxybenzyl)-2-(2-(4-methoxybenzyl)-2H-tetrazol-5-yl)benzenesulfonamide (3.23 g, 4.86 mmol), 5,5,5?,5?-tetramethyl-2,2?-bi(1,3,2-dioxaborinane) (3.29 g, 14.6 mmol), PCy3 Pd G2 (0.287 g, 0.486 mmol), and potassium acetate (1.431 g, 14.58 mmol). Then anhydrous acetonitrile (new bottle, 25 mL) was added to this flask. Nitrogen was bubbled through this mixture for 10 min, then the mixture was heated at 85 C. for 24 hr. The mixture was cooled to room temperature. 1 M NaOH was added to the reaction mixture. The mixture was extracted with EtOAc. The organic phase was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with 0-80% hexane/EtOAc to give the product, which was contaminated by about of de-Br side product.Step A: Palladium Catalyzed C-C Coupling of Arylboronic Ester with Bromides (0866) An isomeric mixture of 3-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-N,N-bis(4-methoxybenzyl)-2-(1-(4-methoxybenzyl)-1H-tetrazol-5-yl)benzenesulfonamide and 3-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-N,N-bis(4-methoxybenzyl)-2-(2-(4-methoxybenzyl)-2H-tetrazol-5-yl)benzenesulfonamide, Reference Example 9, (80 mg, 0.12 mmol), were combined with commercially available or known aryl or heteroaryl bromides (0.138 mmol), cesium carbonate (112 mg, 0.344 mmol) and 2nd Generation Xphos Precatalyst (13.5 mg, 17 mumol) in a 1 dram vial and taken into the glove box. Dioxane (0.8 mL) a...

Reference： [1]Patent: WO2015/112441,2015,A1 .Location in patent: Page/Page column 262
[2]Patent: US2016/333021,2016,A1 .Location in patent: Paragraph 0291; 0292; 0309; 0311; 0866; 0867

12
[ 1266322-58-0 ]
N-(7-phenylquinolin-3-yl)-4-methyl-benzenesulfonamide [ No CAS ]

Reference： [1]New Journal of Chemistry,2016,vol. 40,p. 9034 - 9037

13
[ 1266322-58-0 ]
(R)-N-(7-bromo-1,2,3,4-tetrahydroquinolin-3-yl)-4-methylbenzenesulfonamide [ No CAS ]
(S)-N-(7-bromo-1,2,3,4-tetrahydroquinolin-3-yl)-4-methylbenzenesulfonamide [ No CAS ]

Reference： [1]New Journal of Chemistry,2016,vol. 40,p. 9034 - 9037

14
[ 1266322-58-0 ]
[ 98-59-9 ]
N-(7-bromoquinolin-3-yl)-4-methylbenzenesulfonamide [ No CAS ]

Reference： [1]New Journal of Chemistry,2016,vol. 40,p. 9034 - 9037

15
[ 1266322-58-0 ]
C₉H₅BrFNO [ No CAS ]