[ CAS No. 1073354-91-2 ] {[proInfo.proName]}

Name: 1073354-91-2|5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]thiazole|97%
Brand: Ambeed
SKU: A150133
Price: 12.0 USD
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Quality Control of [ 1073354-91-2 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 1073354-91-2 ]

Product Details of [ 1073354-91-2 ]

CAS No. :	1073354-91-2	MDL No. :	MFCD09260439
Formula :	C₁₃H₁₆BNO₂S	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	MGOKEBHEDJCRQN-UHFFFAOYSA-N
M.W :	261.15	Pubchem ID :	46739030
Synonyms :

Calculated chemistry of [ 1073354-91-2 ]

Physicochemical Properties

Num. heavy atoms :	18
Num. arom. heavy atoms :	9
Fraction Csp3 :	0.46
Num. rotatable bonds :	1
Num. H-bond acceptors :	3.0
Num. H-bond donors :	0.0
Molar Refractivity :	76.1
TPSA :	59.59 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	Yes
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	Yes
CYP3A4 inhibitor :	Yes
Log Kp (skin permeation) :	-5.5 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	3.37
Log Po/w (WLOGP) :	2.6
Log Po/w (MLOGP) :	1.5
Log Po/w (SILICOS-IT) :	3.0
Consensus Log Po/w :	2.09

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.89
Solubility :	0.0339 mg/ml ; 0.00013 mol/l
Class :	Soluble
Log S (Ali) :	-4.3
Solubility :	0.0131 mg/ml ; 0.0000502 mol/l
Class :	Moderately soluble
Log S (SILICOS-IT) :	-4.57
Solubility :	0.007 mg/ml ; 0.0000268 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	0.0
Synthetic accessibility :	2.92

Safety of [ 1073354-91-2 ]

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

Application In Synthesis of [ 1073354-91-2 ]

* 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 [ 1073354-91-2 ]
Downstream synthetic route of [ 1073354-91-2 ]

[ 1073354-91-2 ] Synthesis Path-Upstream 1~1

1
[ 768-11-6 ]
[ 73183-34-3 ]
[ 1073354-91-2 ]

Yield	Reaction Conditions	Operation in experiment
38%	With potassium acetate In dimethyl sulfoxide at 85℃; for 3 h; Inert atmosphere	A mixture of 5-bromobenzo[c/\|thiazole (428 mg, 2.00 mmol), bis(pinacolato)diboron (558 mg, 2.20 mmol) and potassium acetate (588 mg, 6.00 mmol) in dimethyl sulfoxide (7 mL) was sparged with nitrogen while stirring for 5 min. Dichloro 1 ,1-bis(diphenylphosphino)ferrocene palladium(ll) dichloromethane (293 mg, 0.40 mmol) was then added and the reaction stirred at 85 ⁰C for 3 h. After this time, the mixture was filtered through a pad of Celite and the filter cake was washed with ethyl acetate (75 mL) then water (20 mL). The filtrate was diluted with ethyl acetate (100 mL) and washed with water (2 x 75 ml_), then brine (75 ml_). The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by chromatography (silica, gradient 0percent to 50percent ethyl acetate in methylene chloride) to afford 5-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2- yl)benzo[d]thiazole (3) (200 mg, 38percent) as a light brown solid: ¹H NMR (300 MHz, DMSO-cfe) δ 9.41 (s, 1 H), 8.32 (s, 1 H), 8.18 (d, 1 H, J = 8.0 Hz), 7.72 (d, 1 H, J = 8.0 Hz), 1.33 (s, 12H); ESI MS m/z 262.1 [M + H]⁺.

Reference： [1] Patent: WO2010/68257, 2010, A1, . Location in patent: Page/Page column 92-93
[2] Patent: WO2009/14637, 2009, A2, . Location in patent: Page/Page column 173-174
[3] Patent: WO2011/66211, 2011, A1, . Location in patent: Page/Page column 86-87
[4] Patent: CN108707139, 2018, A, . Location in patent: Paragraph 0612; 0614; 0655; 0656; 0657; 0658

[ 1073354-91-2 ] Synthesis Path-Downstream 1~30

1
[ 768-11-6 ]
[ 73183-34-3 ]
[ 1073354-91-2 ]

Yield	Reaction Conditions	Operation in experiment
38%	With potassium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In dimethyl sulfoxide; at 85℃; for 3h;Inert atmosphere;	A mixture of 5-bromobenzo[c/\|thiazole (428 mg, 2.00 mmol), bis(pinacolato)diboron (558 mg, 2.20 mmol) and potassium acetate (588 mg, 6.00 mmol) in dimethyl sulfoxide (7 mL) was sparged with nitrogen while stirring for 5 min. Dichloro 1 ,1-bis(diphenylphosphino)ferrocene palladium(ll) dichloromethane (293 mg, 0.40 mmol) was then added and the reaction stirred at 85 0C for 3 h. After this time, the mixture was filtered through a pad of Celite and the filter cake was washed with ethyl acetate (75 mL) then water (20 mL). The filtrate was diluted with ethyl acetate (100 mL) and washed with water (2 x 75 ml_), then brine (75 ml_). The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by chromatography (silica, gradient 0% to 50% ethyl acetate in methylene chloride) to afford 5-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2- yl)benzo[d]thiazole (3) (200 mg, 38%) as a light brown solid: 1H NMR (300 MHz, DMSO-cfe) delta 9.41 (s, 1 H), 8.32 (s, 1 H), 8.18 (d, 1 H, J = 8.0 Hz), 7.72 (d, 1 H, J = 8.0 Hz), 1.33 (s, 12H); ESI MS m/z 262.1 [M + H]+.
	With potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In dimethyl sulfoxide; at 100℃; for 0.5h;Microwave irradiation;	Compound 418:Scheme-28: <n="175"/>Compound 418:A 10 ml_ microwave vial was charged with 5-bromobenzothiazole (214 mg, 1 mmol), bis(pinacolato)diboron (381 mg, 1.5 mmol), Pd(ddpf)Cl2 (40 mg, 0.05 mmol), potassium acetate (490 mg, 5 mmol) and DMSO (5 ml_). The reaction was irradiated with stirring for 30 minutes at 100 C. The reaction was partitioned between water and EtOAc. The organic phase was separated and concentrated, then purified by silica gel chromatography (1 :9 EtOAc/Hexane) to yield compound 418 as a waxy solid. HPLC-MS tR = 2.01 min (ELSD); Mass calculated for C13H16BNO2S: 261.1 ; Observed m/z: 262.1 (M+H).
	With potassium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; at 100℃; for 1h;Inert atmosphere;	A solution of 5-bromo-l,3-benzothiazole (0.148 mmol) in anhydrous dioxane (1 mL) was treated with bis(pinocolato)diboron (0.141 mmol), dichloro[l ,l '- bis(diphenylphosphino)ferrocene]palladium(II)-dichloromethane adduct (5.7 mg), and potassium acetate (0.423 mmol). The reaction mixture was purged with nitrogen gas, sealed, and stirred at 100 C for 1 h. The black reaction mixture was then cooled to room temperature, and analysis by LC/MS confirmed the conversion of the starting material to its boronate ester. The solution was then treated with 2-(4-bromophenyl)-l-[(3S)-l- (cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-lH-imidazo[4,5-c]pyridine (0.141 mmol), dichloro[l,l '-bis(diphenylphosphino)ferrocene]palladium(II)-dichloromethane adduct (5.7 mg), and 2M aq potassium carbonate (0.42 mmol). The reaction mixture was purged with nitrogen, sealed, and stirred at 100 C overnight. The reaction mixture was cooled to room temperature and was diluted with water (50 mL). The aqueous layer was acidified to pH ~7 using IN aq HC1 and was extracted with dichloromethane. The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. The brown residue was purified by reverse phase HPLC (LUNA C-18: 30x50 mm column; 0- 30% acetonitrile w/ 0.1% TFA/water w/ 0.1% TFA). The product fractions were neutralized with the addition of saturated aq sodium bicarbonate, concentrated under reduced pressure, and extracted with dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo to afford the title compound as a beige solid (20 mg, 28%). MS(ES)+ m/e 480.1 [M+H]+.

With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In N,N-dimethyl-formamide; at 100℃; for 7h;Inert atmosphere;

General procedure: Under argon protection,Add to the 100mL single-mouth bottle5-bromo-1-methyl-6-(trifluoromethyl)-1H-indazole(500mg, 1.79mmol),Bis(pinacolato)diboron(685.2mg, 2.69mmol),Potassium acetate (352.5 mg, 3.58 mmol),Pd(dppf)Cl2 (131.6 mg, 0.179 mmol)And dioxane (15mL), plus,The temperature was raised to 100 C for 7 h.The reaction system was cooled to room temperature, and 20 mL of water was added to the reaction solution.The aqueous phase was extracted three times with ethyl acetate (50 mL×3).The crude product was purified by column chromatography.The product was eluted with PE/EA = 10/1, and the product was collected and concentrated to give 300 mg of pale yellow oil, yield: 51.1%.

Reference： [1]Patent: WO2010/68257,2010,A1 .Location in patent: Page/Page column 92-93
[2]Patent: WO2009/14637,2009,A2 .Location in patent: Page/Page column 173-174
[3]Patent: WO2011/66211,2011,A1 .Location in patent: Page/Page column 86-87
[4]Patent: CN108707139,2018,A .Location in patent: Paragraph 0612; 0614; 0655; 0656; 0657; 0658

2
[ 1073354-91-2 ]
[ 1186604-81-8 ]
[ 1186605-08-2 ]

Yield	Reaction Conditions	Operation in experiment
54.4%	With potassium phosphate;palladium diacetate; triphenylphosphine; In 1,4-dioxane; water; at 20 - 100℃;Inert atmosphere;	Step 1: Preparation of 4-[3-[6-(3-benzothiazol-5-yl-5-methanesulfonyl-phenoxy)-hexyl]-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric Acid Ethyl Ester To a mixture of benzothiazole-5-ylboronic acid pinacol ester (151.5 mg, 0.58 mmol), palladium acetate(II) (6.6 mg, 0.029 mmol), and triphenylphosphine (15.4 mg, 0.058 mmol) in dioxane (5 mL) were added 4-{2-(2-ethoxycarbonyl-ethyl)-3-[6-(3-iodo-5-methanesulfonyl-phenoxy)-hexyl]-phenoxy}-butyric acid ethyl ester (200 mg, 0.29 mmol), potassium phosphate (126.9 mg, 0.58 mmol), and water (10 mg) at room temperature under nitrogen atmosphere. Then, the brown reaction mixture was heated to 100 C. and stirred for 2 h at which time the TLC of the reaction mixture indicated the absence of starting material. Then, the reaction mixture was cooled to room temperature and diluted with water (50 mL) and ethyl acetate (50 mL). The two layers were separated and the aqueous layer was extracted with ethyl acetate (50 mL) and the combined organic extracts were washed with water (100 mL) and brine solution (100 mL). The organic layer was dried over anhydrous magnesium sulfate and filtration of the drying agent and removal of the solvent under reduced pressure gave the colored residue which was purified by using an ISCO 40 g column, eluding with 2-25% ethyl acetate in hexanes to afford 4-[3-[6-(3-benzothiazol-5-yl-5-methanesulfonyl-phenoxy)-hexyl]-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl ester (110 mg, 54.4%) as a light brown solid: ES(+)-HRMS m/e calcd for C37H45NO8S2 (M+H)+ 696.2660, found 696.2658.

Reference： [1]Patent: US2009/227603,2009,A1 .Location in patent: Page/Page column 51

3
[ 870188-37-7 ]
[ 1073354-91-2 ]
[ 1210047-48-5 ]

Yield	Reaction Conditions	Operation in experiment
16%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 110℃; for 0.25h;Inert atmosphere;	Under an argon atmosphere, 340 mg (0.790 mmol) of methyl-2-[4-bromo-3 -methyl- 1 -(2- methylphenyl)-lH-pyrazol-5-yl]amino}-5-methoxybenzoate (described in WO 2005/112923, p. 18) and 620 mg (2.374 mmol) of 5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-l,3-benzothiazole dissolved in 8.4 ml dimethylformamide and 1.975 ml of 2N aqueous sodium carbonate solution and 55 mg (0.047 mmol) of tetrakis(triphenylphosphine)palladium(0) were added. The mixture was stirred for 15 min at 1100C. After cooling, water was added and it was extracted with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated in a rotary evaporator at reduced pressure. The residue was purified by preparative HPLC (eluent: acetonitrile/water, gradient 10:90 ? 90: 10). We obtained 60 mg (16% of theor.) of the target compound.LC-MS (method 4): R, = 1.39 min; MS (EIpos): m/z = 485 [M+H]+.1H-NMR (400 MHz, DMSO-D6): delta [ppm] = 2.16 (s, 3H), 2.41 (s, 3H), 3.57 (s, 3H), 3.78 (s, 3H), 6.43 (d, IH), 6.84 (dd, IH), 7.13 (d, IH), 7.20-7.25 (m, IH), 7.28-7.32 (m, 2H), 7.38 (d, IH), 7.56 (dd, IH), 8.10-8.12 (m, 2H), 8.84 (s, IH), 9.36 (s, IH).

Reference： [1]Patent: WO2010/20363,2010,A1 .Location in patent: Page/Page column 70-71

4
[ 1073354-91-2 ]
[ 1210043-68-7 ]
[ 1210043-92-7 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; ethanol; at 110℃; for 0.5h;Inert atmosphere; Microwave irradiation;	To a solution of 7 (49 mg, 0.1 mmol) in 1,2-dimethoxyethane (DME, 2 mL) and EtOH (1 mL) was added 37 (31 mg, 0.12 mmol), 0.5 M NaHCO3 (1 mL). The suspension was bubbled with argon for 5 min before adding Pd(PPh3) (38, 12 mg, 0.01 mmol). The reaction mixture was heated at 110 C for 30 min using microwave initiator. The solid was filtered off and the filtrate was extracted with EtOAc (10ml x 2). The combined organic layers were dried (Na2SO4) and concentrated in vacuo. The compound 39 was purified by HPLC. The 39 was dissolved in CH2Cl2 (2 ml) and TFA (0.5 ml) was added. The mixture was stirred for 2 h at r.t. The solvent was removed in vacuo. The residue was treated with MeOH (2 mL) and the solid was collected by centrifuge and washed with MeOH. Compound 40 (20 mg, 48 %) was obtained as yellow solid. LC-MS: calcd. for C2iH12N2O4S2: 419 (M -I).

Reference： [1]Patent: WO2010/25295,2010,A2 .Location in patent: Page/Page column 129-130

5
[ 1073354-91-2 ]
[ 1181329-13-4 ]
[ 1229205-59-7 ]

Yield	Reaction Conditions	Operation in experiment
70%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 135℃; for 0.5h;Inert atmosphere; Microwave irradiation;	A mixture of 6-bromo-Lambda/-(3,4- dimethoxyphenyl)imidazo[1 ,2-a]pyrazin-8-amine (2) (209 mg, 0.601 mmol), and 5- (4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)benzo[d]thiazole (3) (180 mg, 0.689 mmol) in 1 M aqueous sodium carbonate (0.76 ml_) and 1 ,4-dioxane (2.4 mL) was sparged with nitrogen while stirring for 5 min. Tetrakis(triphenyl-phosphine) palladium(O) (69 mg, 0.06 mmol) was then added and the resulting mixture reacted under microwave irradiation at 135 0C for 30 min. After this time, the reaction was cooled to ambient temperature, diluted with 1 :9 methanol/ethyl acetate (75 mL), and washed with water (50 mL) then brine (50 mL). The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by chromatography (silica, gradient 0% to 10% methanol in methylene chloride) to afford 6-(benzo[alphaf\|thiazol-5-yl)-Lambda/-(3,4-dimethoxyphenyl)imidazo[1 ,2-a]pyrazin-8-amine (4) (169 mg, 70%) as an off-white solid: mp 179-181 0C; 1H NMR (300 MHz, DMSO- cfe) delta 9.56 (s, 1 H), 9.45 (s, 1 H), 8.78 (s, 1 H), 8.76 (d, 1 H, J = 1.2 Hz), 8.26 (d, 1 H1 J = 8.7 Hz), 8.14 (m, 2H), 8.00 (s, 1H), 7.66 (s, 1 H), 7.58 (dd, 1 H, J = 8.7, 2.4 Hz), 6.99 (d, 1 H, J= 8.7 Hz), 3.87 (s, 3H), 3.76 (s, 3H); MS m/z 404.6 [M + H]+; HPLC, 6.475 min, 98.6% (AUC).

Reference： [1]Patent: WO2010/68257,2010,A1 .Location in patent: Page/Page column 93

6
[ 1073354-91-2 ]
[ 1246206-41-6 ]
[ 1246206-55-2 ]

Yield	Reaction Conditions	Operation in experiment
99%	With potassium phosphate;palladium diacetate; In 1,4-dioxane; water; at 20 - 100℃;	Step 1: 4-[3-{6-(3-Benzothiazol-5-yl-5-ethoxy-phenoxy)-hexyl}-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl ester To a suspension of palladium(II) acetate (11.32 mg, 0.05 mmol), triphenyphosphine (26.2 mg, 0.1 mmol), and benzothiazol-5-yl pinacolboronate (258 mg, 0.99 mmol) in dioxane (7.5 mL) were added 4-[3-[6-(3-bromo-5-ethoxy-phenoxy)-hexyl]-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl ester (300 mg, 0.49 mmol), potassium phosphate (216 mg, 0.99 mmol), and pure water (15 mg, 0.99 mmol) at room temperature. Then, the resulting mixture was heated to 100 C. for 2 h. Then, the reaction mixture was cooled to room temperature and diluted with water (50 mL) and ethyl acetate (50 mL). The two layers were separated and the aqueous layer was extracted with ethyl acetate (50 mL) and the combined organic extracts were washed with water (50 mL) and brine solution (50 mL). The organic layer was dried over anhydrous magnesium sulfate and filtration of the drying agent and removal of the solvent under vacuum gave the colored residue which was purified by using an ISCO 40 g column, eluding with 2-25% ethyl acetate in hexanes to obtain 4-[3-{6-(3-benzothiazol-5-yl-5-ethoxy-phenoxy)-hexyl}-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl ester (61 mg, 99%) as a off-white solid: ES(+)-LRMS m/e calcd for C38H47NO7S (M+H)+ 662.3146, found 662.3144.

Reference： [1]Patent: US2010/240678,2010,A1 .Location in patent: Page/Page column 64-65

7
[ 1073354-91-2 ]
[ 1396750-35-8 ]
[ 1396752-42-3 ]

Yield	Reaction Conditions	Operation in experiment
69%	With potassium phosphate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 90℃; for 1h;Inert atmosphere;	Step 1. Methyl 2-(l,3-benzothiazol-5-yl)-3-[(25')-2-methylpyrrolidin-l-yl]quinoxaline-6-To a solution of methyl 3-[(25')-2-methylpyrrolidin-l-yl]-2-[(trifluoromethane)sulfonyloxy]quinoxaline-6-carboxylate (150 mg, 0.36 mmol) in dioxane (6 mL) was added 5-(tetramethyl-l ,3,2-dioxaborolan-2-yl)-l ,3-benzothiazole (280 mg, 1.07 mmol), Pd(PPh3)4 (21 mg, 0.02 mmol), K3P04 (228 mg, 1.07 mmol) and water (5 drops). The resulting solution was stirred for 1 h at 90C maintained with an inert atmosphere of nitrogen in an oil bath. The reaction mixture was concentrated in vacuo to give the residue, which was applied onto silica gel column chromatography eluting with 1% to 5% ethyl acetate in petroleum to afford methyl 2-(l ,3-benzothiazol-5-yl)-3-[(25')-2-methylpyrrolidin-l- yl]quinoxaline-6-carboxylate as a yellow solid (100 mg, 69%).LC/MS (ES, m/z): [M+H]+ 405.0'H-NMR (300 MHz, CDC13) delta 9.12 (s, 1Eta), 8.73 (s, 1Eta), 8.52 (s, 1Eta), 7.92 - 8.14 (m, 4Eta),4.50 - 4.60 (m, 1Eta), 4.01 (s, 3Eta), 3.17 - 3.24 (m, 1Eta), 2.95 - 3.05 (m, 1Eta), 2.15 - 2.25 (m,1Eta), 1.81 - 1.91 (m, 1Eta), 1.60 - 1.75 (m, 2Eta), 1.45 (d, / = 5.7 Hz, 3H)

Reference： [1]Patent: WO2012/119046,2012,A2 .Location in patent: Page/Page column 126-127

8
[ 1073354-91-2 ]
[ 1394973-22-8 ]
[ 1396752-39-8 ]

Reference： [1]Patent: WO2012/119046,2012,A2

9
[ 1073354-91-2 ]
[ 1394973-22-8 ]
[ 1396752-40-1 ]

Yield	Reaction Conditions	Operation in experiment
83%	With potassium phosphate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 90℃; for 1h;	Step 1. Methyl 2-(benzo[if\|thiazol-5-yl)-3-(isopropyl(methyl)amino)quinoxaline-6-To a solution of methyl 3-(isopropyl(methyl)amino)-2-(trifluoromethylsulfonyloxy)quinoxaline-6-carboxylate (150 mg, 0.37 mmol) in dioxane (5 mL) was added 5-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)benzo[if\|thiazole (288 mg, 1.1 mmol), K3P04 (234 mg, 1.1 mmol), Pd(PPh3)4 (21 mg, 0.018 mmol) and water (3 drops). The resulting solution was stirred for 1 h at 90C and then concentrated in vacuo to give a residue, which was purified by silica gel column chromatography eluting with 2% - 5% ethyl acetate in petroleum ether to afford methyl 2-(benzo[<i]thiazol-5-yl)-3- (isopropyl(methyl)amino)quinoxaline-6-carboxylate as a yellow solid (120 mg, 83%). LC/MS (ES, m/z):[M+H]+ 393.0'H-NMR (300 MHz, CDC13): delta 9.10 (s, 1H), 8.70 (d, / = 0.9 Hz, 1H), 8.63 (d, / = 1.5 Hz, 1H), 8.00 - 8.13 (m, 4H), 4.29 - 4.38 (m, 1H), 4.01 (s, 3H), 2.81 (s, 3H), 1.10 (d, / = 6.6 Hz, 6H

Reference： [1]Patent: WO2012/119046,2012,A2 .Location in patent: Page/Page column 125-126

10
[ 1073354-91-2 ]
2-(4-bromophenyl)-1-[1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-1H-imidazo[4,5-c]pyridine [ No CAS ]
2-[4-(1,3-benzothiazol-5-yl)phenyl]-1-[1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-1H-imidazo[4,5-c]pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; water; at 100℃;Inert atmosphere;	A solution of 5-bromo-l,3-benzothiazole (0.148 mmol) in anhydrous dioxane (1 mL) was treated with bis(pinocolato)diboron (0.141 mmol), dichloro[l ,l '- bis(diphenylphosphino)ferrocene]palladium(II)-dichloromethane adduct (5.7 mg), and potassium acetate (0.423 mmol). The reaction mixture was purged with nitrogen gas, sealed, and stirred at 100 C for 1 h. The black reaction mixture was then cooled to room temperature, and analysis by LC/MS confirmed the conversion of the starting material to its boronate ester. The solution was then treated with 2-(4-bromophenyl)-l-[(3S)-l- (cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-lH-imidazo[4,5-c]pyridine (0.141 mmol), dichloro[l,l '-bis(diphenylphosphino)ferrocene]palladium(II)-dichloromethane adduct (5.7 mg), and 2M aq potassium carbonate (0.42 mmol). The reaction mixture was purged with nitrogen, sealed, and stirred at 100 C overnight. The reaction mixture was cooled to room temperature and was diluted with water (50 mL). The aqueous layer was acidified to pH ~7 using IN aq HC1 and was extracted with dichloromethane. The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. The brown residue was purified by reverse phase HPLC (LUNA C-18: 30x50 mm column; 0- 30% acetonitrile w/ 0.1% TFA/water w/ 0.1% TFA). The product fractions were neutralized with the addition of saturated aq sodium bicarbonate, concentrated under reduced pressure, and extracted with dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo to afford the title compound as a beige solid (20 mg, 28%). MS(ES)+ m/e 480.1 [M+H]+.

Reference： [1]Patent: WO2011/66211,2011,A1 .Location in patent: Page/Page column 86-87

11
[ 1073354-91-2 ]
[ 1549775-51-0 ]
[ 1549771-13-2 ]

Yield	Reaction Conditions	Operation in experiment
0.118 g	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In water; N,N-dimethyl-formamide; at 90℃; for 16h;Inert atmosphere;	General procedure: 10347] To a sealed tube under argon atmosphere was added6-bromo-2-(thran-2-yl)-N-(pyridin-3-yl)quinoline-4-car- boxamide (0.250 g) in DMF (5 ml), and the vessel was purged with argon under stirring for 5 minutes. Afier 5 minutes, 2N solution of sodium carbonate in water (3.3 ml) was added and the tube was purged with argon under stirring for 5 minutes. Phenylboronic acid (0.115 g) was then added and the tube was purged with argon under stirring for 15 minutes. Finally, palladium(0)tetrakis triphenylphosphine (0.034 g) was added under argon and the tube was sealed and heated to 90 C. for 16 hours. The completion of the reaction was monitored by TLC using ethyl acetate:hexanes (5:5) as a mobile phase. Afier completion of the reaction, the reaction mixture was diluted with ethyl acetate (100 ml) and then washed with water (5 * 100 ml). The ethyl acetate layer was dried over anhydrous sodium sulphate, and the solvent was removed by distillation and the crude product was subjected to purification by silica gel column chromatography, eluting with 1-2% methanol in methylene chloride to provide 0.154 g of 2-(fu- ran-2-yl)-6-phenyl-N-(pyridin-3-yl)quinoline-4-carboxamide (1). The title compound was prepared using the methods shown in Scheme 1 with the appropriate amine (3-pyridylamine) and boronic ester (<strong>[1073354-91-2]5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]thiazole</strong>) reagents to provide the target compound (0.118 g). 1H NMR (400 MHz, DMSO-d6) delta ppm 11.16 (s, 1H), 9.49 (s, 1H), 8.99 (s, 1H), 8.50 (m, 2H), 8.40 (m, 1H), 8.33 (m, 3H), 8.27 (s, 1H), 8.22 (m, 1H), 8.05 (m, 1H), 7.94 (m, 1H), 7.56 (m, 1H), 7.47 (m, 1H), 6.60 (m, 1H); m/z 449.1 (MH+).

Reference： [1]Patent: US2014/221387,2014,A1 .Location in patent: Paragraph 0347; 0364

12
[ 1073354-91-2 ]
[ 1620098-61-4 ]
C₂₉H₂₈F₆N₆O₅S₂ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 5949 - 5964

13
[ 1073354-91-2 ]
(4-(4-bromobenzoyl)piperazin-1-yl)(1-hydroxycyclopropyl)methanone [ No CAS ]
(4-(4-(benzo[d]thiazol-5-yl)benzoyl)piperazin-1-yl)(1-hydroxycyclopropyl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
35%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 50℃; for 1h;Microwave irradiation;	Tetrakis(triphenylphosphine)palladium(0) (0.016 g, 0.014 mmol) was added to a mixture of (4-(4-bromobenzoyl)piperazin-l-yl)(l-hydroxycyclopropyl)methanone (0.050 g, 0.142 mmol), 5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)benzo[d]thiazole (0.055 g, 0.212 mmol), and sodium carbonate (0.060 g, 0.566 mmol) in dioxane (1.5 mL) and water (0.30 mL). The mixture stirred in the microwave at 50 C for 1 h. The reaction mixture was filtered through Celite and concentrated to afford a yellow oil. This material was purified via column chromatography on silica gel (Biotage 25 g column, gradient elution with 0- 5% methanol-ethyl acetate) to afford (4-(4-(benzo[d]thiazol-5-yl)benzoyl)piperazin-l- yl)(l-hydroxycyclopropyl)methanone (0.020 g, 0.049 mmol, 35 % yield) as an off-white solid. MS (ESI, pos. ion) m/z: 408 (M + 1).

Reference： [1]Patent: WO2014/164749,2014,A1 .Location in patent: Page/Page column 239

14
[ 1073354-91-2 ]
3-bromo-5-(methylamino)-1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-carbonitrile [ No CAS ]
3-(1,3-benzothiazol-5-yl)-5-(methylamino)-1-(2,2,2-trifluoroethyl)-1H-pyrazole-4-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate; In 1,4-dioxane; water; at 120℃; for 20h;Inert atmosphere; Sealed tube; Microwave irradiation;	Intermediate 7: 3-(l,3-benzothiazol-5-yn-5-(methylamino)-l-(2,2,2-trifluoroethyn-lH- pyrazole-4-carbonitrile A 20 ml. microwave vial was charged with 3-bromo-5-(methylamino)-l-(2,2,2- trifluoroethyl)-lH-pyrazole-4-carbonitrile (Intermediate 6; 230 mg, 0.813 mmol), 5- (4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-l,3-benzothiazole (318 mg, 1.219 mmol) purchased from ASDI, 1,4-Dioxane (130 ml.) and an aqueous solution of sodium carbonate 2M (1.219 ml_, 2.438 mmol). The reaction was purged with argon for 5 min, then PdCI2(dppf)-CH2Cl2 adduct (133 mg, 0.163 mmol) purchased from Aldrich (catalog number 379670) was added. The vessel was sealed and heated in an 120C heating block. After 20 hours the reaction was cooled to room temperature, dried with MgS04, filtered and concentrated. The crude material was purified on Biotage (50g SNAP column, 10-100% EtOAc/Hexanes). Desired product elutes at 100% EtOAc to yield 225 mg of a pinkish solid (0.534 mmol, 80% purity, 65 %yield), used as such in the next step. 1H NMR (400 MHz, DMSO-d6): delta 9.08 (s, 1H), 8.70 (bs, 1H), 8.00 (m, 2H), 4.60 (dd, 2H), 3.36 (s, 3H). LCMS: M/Z = 338.2 (M+l)

Reference： [1]Patent: WO2016/55607,2016,A1 .Location in patent: Page/Page column 25; 26

15
[ 1073354-91-2 ]
tert-butyl (2S)-2-[(1S)-1-cyano-2-(4-iodophenyl)ethyl]carbamoyl}-1,4-oxazepane-4-carboxylate [ No CAS ]
C₂₇H₃₀N₄O₄S [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 9457 - 9472

16
[ 1073354-91-2 ]
8-chloro-N-(4-methanesulfonylpyridin-3-yl)quinoxalin-6-amine [ No CAS ]
8-(1,3-benzothiazol-5-yl)-N-(4-methanesulfonylpyridin-3-yl)quinoxalin-6-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
9%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,2-dimethoxyethane; water; at 110℃;Inert atmosphere; Sealed tube;	A pressure vessel is loaded with 8-chloro-A/-(4-methanesulfonylpyridin-3- yl)quinoxalin-6-amine (Intermediate 3B, 70 mg; 0.21 mmol; 1 eq.), 5-(4,4,5,5- tetramethyl-[1 ,3,2]dioxaborolan-2-yl)benzothiazole (109 mg; 0.42 mmol; 2 eq.), sodium carbonate (66 mg; 0.63 mmol; 3 eq.), DME (2 ml_) and water (1 mL). The mixture is degassed by argon bubbling and sonication before Pd(dppf)CI2 (15 mg; 0.02 mmol; 0.10 eq.) is added. The tube is sealed and heated at 110 C overnight. After cooling to room temperature the reaction mixture is filtered through a pad of celite and the filtrate is partitioned between EtOAc and water. The combined organic phases are washed with brine, dried over Na2S04, filtered and concentrated. The residue is purified by FCC (0-5% MeOH gradient in DCM) and followed by reversed-phase preparative HPLC (column: Gemini NX C18 5u 1 10A (100x30 mm), ACN gradient in water) to give 8-(1 ,3-benzothiazol-5-yl)-A/-(4- methanesulfonylpyridin-3-yl)quinoxalin-6-amine as its TFA salt (10 mg; 0.02 mmol; yield: 9%; orange powder; HPLC purity: >99%) .

Reference： [1]Patent: WO2016/180537,2016,A1 .Location in patent: Page/Page column 111; 112

17
[ 1073354-91-2 ]
8-chloro-N-(4-methanesulfonylpyridin-3-yl)quinoxalin-6-amine [ No CAS ]
[ 76-05-1 ]
8-(1,3-benzothiazol-5-yl)-N-(4-methanesulfonylpyridin-3-yl)quinoxalin-6-amine trifluoroacetate [ No CAS ]

Reference： [1]ChemMedChem,2019,vol. 14,p. 169 - 181

18
[ 1073354-91-2 ]
7-bromo-6-vinyl-1H-imidazo[4,5-c]pyridine [ No CAS ]
[ 141776-91-2 ]
1-(7-(benzo[d]thiazol-5-yl)-1H-imidazo[4,5-c]pyridin-6-yl)-2-(3,5-difluorophenyl)ethanamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.08 g		N-((7-bromo-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazo[4,5-c]pyridin-6- yl)methylene)-2- amide (Int 13h) (0425) To a stirred solution of 7-bromo-l-((2-(trimethylsilyl)ethoxy)methyl)-lH- imidazo[4,5-c]pyridine-6-carbaldehyde (4.00 g, 11.23 mmol) in DCM (60 mL) was added 2-methylpropane-2-sulfinamide (1.50 g, 12.35 mmol), copper(II) sulfate (3.58 g, 22.45 mmol) and the reaction mixture was stirred at RT for 16 h. The reaction mixture was diluted with DCM (100 mL), filtered through Celite and the filtrate concentrated. The crude product was purified by Combiflash chromatography (40 g Redisep SiC column, eluting with 6% methanol in chloroform) to afford the title compound (3.5 g) as an off white gummy solid. LC/MS retention time = 1.36 min, m/z = 459.4 [M+H]+. ACQUITY BEH C18 (3 X 50) mm, 1.7 muetaiota; Flow rate: 0.7 mL/min; Mobile Phase A: 5 mmol NH4OAc in 95% Water/ 5% ACN; Mobile Phase B: 5 mmol NH4OAc in 5% Water/ 95% ACN; 20% B to 100% B over 1 mm, then hold for 0.6 min at 90% B; Detection: UV at 220 nm. [Note: although a single peak was observed in LC/MS analysis, it was not apparent if the sample contained one SEM-regioisomer or not. Also, the SEM disposition for the dominant isomer, although ultimately inconsequential, was not established]. (0426) N-((7-(benzo[d]thiazol-5-yl)-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazo[4,5- c]pyridin-6-yl)methyl -2-sulfmamide (Int 13i) (0427) (0428) To a stirred solution of N-((7-bromo-l-((2-(trimethylsilyl)ethoxy)methyl)-lH- imidazo[4,5-c]pyridin-6-yl)methylene)-2-methylpropane-2-sulfmamide (0.65 g, 1.42 mmol) in DMF (2 mL) was added 5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2- yl)benzo[d]thiazole (0.48 g, 1.84 mmol) and K2CO3 (0.59 g, 4.24 mmol) and the reaction mixture was purged with N2 for 15 min. Pd(PPli3)4 (0.098 g, 0.085 mmol) was added and the reaction mixture was heated to 100 C and stirred for 2 h. The reaction mixture was concentrated to remove DMF, the residue was treated with water (50 mL) and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulphate, filtered, concentrated and the crude product was purified by Combiflash chromatography (40 g Redisep S1O2 column, eluting with 5 % methanol in chloroform) to afford the title compound (0.80 g) as brown solid. LC/MS retention time = 1.45 min, m z = 514.6 (0429) [M+H]+. ACQUITY BEH C18 (3 X 50) mm, 1.7 muiotaeta; Flow rate: 0.7 mL/min; Mobile (0430) Phase A: 5 mmol NH4OAc in 95% Water/ 5% ACN; Mobile Phase B: 5 mmol NH4OAc in 5% Water/ 95% ACN; 20% B to 100% B over 1 min, then hold for 0.6 min at 90% B; Detection: UV at 220 nm. [Note: although a single peak was observed in LC/MS analysis, it was not apparent if the sample contained one SEM-regioisomer or not. Also, the SEM disposition for the dominant isomer, although ultimately inconsequential, was not established] . (0431) N-(l-(7-(benzo[d]thiazol-5-yl)-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-irnidazo[4,5- c]pyridin-6-yl)-2-(3,5-difluoroph lpropane-2-sulfinamide (Int 13j) (0432) (0433) To a stirred mixture of magnesium turning (0.047 g. 1.95 mmol) in diethyl ether (5 mL) was added l-(bromomethyl)-3,5-difluorobenzene (0.252 mL, 1.946 mmol) and the reaction mixture was stirred at RT for 1 h to afford the Grignard reagent. To a stirred solution of N-((7-(benzo [d]thiazol-5 -yl)- 1 -((2-(trimethy lsily l)ethoxy )methy 1)- 1H- iimdazo[4,5-c]pyridin-6-yl)methylene)-2-methylpropane-2-sulfmamide (0.5 g, 0.97 mmol) in diethyl ether (20 mL) at -30 C was added drop wise the Grignard reagent prepared above and the reaction mixture was stirred at RT for 6 h. The reaction mixture was quenched with NH4CI solution and extracted with ethyl acetate (2 x 50 mL). The combined organic layer was dried over anhydrous sodium sulphate, filtered and concentrated to afford crude title compound (0.90 g) as brown gummy solid. The crude compound as such was taken for next step without further purification. LC/MS retention time = 1.69 min, m/z = 642.6 [M+H]+. ACQUITY BEH C 18 (3 X 50) mm, 1.7 muiotaeta; Flow rate: 0.7 mL/min; Mobile Phase A: 5 mmol NH4OAc in 95% Water/ 5% ACN; Mobile Phase B: 5 mmol NH4OAc in 5% Water/ 95% ACN; 20% B to 100% B over 1 min, then hold for 0.6 min at 90% B; Detection: UV at 220 nm. [Note: although a single peak was observed in LC/MS analysis, it was not apparent if the sample contained one SEM- regioisomer or not. Also, the SEM disposition for the dominant isomer, although ultimately inconsequential, was not established] l-(7-(benzo[d]thiazol-5-yl)-lH-imidazo[4,5-c]pyridin-6-yl)-2-(3,5- difluoro (Int 13k) (0434) (0435) To a solution of N-(l-(7-(benzo[d]thiazol-5-yl)-l-((2- (trimethylsilyl)ethoxy)methyl)-lH-imidazo[4,5-c]pyridin-6-yl)-2-(3,5- difluorophenyl)ethyl)-2-methylpropane-2-sulfinamide (0.80 g, 1.25 mmol) in 1,4-dioxane (10 mL) was added 4M HC1 in 1,4-dioxane (5.2 mL, 24 mmol) and the reaction mixture was stirred at RT for 6 h. The reaction mixture was concentrated and the crude compound was purified by preparati...

Reference： [1]Patent: WO2018/203235,2018,A1 .Location in patent: Page/Page column 80-84

19
[ 1073354-91-2 ]
tert-butyl (1-(6-bromothiazolo[4,5-b]pyridin-5-yl)-2-(3,5-difluorophenyl)ethyl)carbamate [ No CAS ]
tert-butyl (1-(6-(benzo[d]thiazol-5-yl)thiazolo[4,5-b]pyridin-5-yl)-2-(3,5-difluorophenyl)ethyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
27 mg	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium hydrogencarbonate; In 1,4-dioxane; at 140℃; for 1h;Microwave irradiation; Inert atmosphere;	To a microwave vial was added tert-butyl (l-(6-bromothiazolo[4,5-b]pyridin-5-yl)- 2-(3,5-difluorophenyl)ethyl)carbamate (50 mg, 0.106 mmol),5-(4,4,5,5-tetramethyl-l,3,2- dioxaborolan-2-yl)benzo[d]thiazole (33.3 mg, 0.128 mmol) followed by 1,4-Dioxane (3 mL) and IN sodium bicarbonate (0.638 mL, 0.638 mmol) and the mixture was degassed for 10 min. PdCb.(dppf)-CH2Cl2 adduct (8.7 mg, 10.6 muiotaetaomicron) was then added and the mixture was heated in microwave at 140 C for 1 h. Mixture was then diluted with ethyl acetate (25 mL) and washed with water (10 mL) and brine (10 mL), dried ( a2S04), filtered and concentrated. The residue was then purified by Biotage (5-80% (0120) EtOAc/hexanes) to afford the title product (27 mg) as off-white solid. (0121) NMR (400 MHz, CDCb) delta 9.45 - 9.37 (m, 1H), 9.11 (s, 1H), 8.20 (s, 1H), 8.06 (d, J=8.3 Hz, 1H), 7.84 - 7.75 (m, 1H), 7.32 (br d, J=4.5 Hz, 1H), 6.63 - 6.49 (m, 1H), 6.17 (br d, J=6.3 Hz, 2H), 6.09 - 5.97 (m, 1H), 5.50 - 5.32 (m, 1H), 3.01 (br d, J=7.0 Hz, 2H), 1.41(s, 9H). LC/MS (M+H)+ = 525.60

Reference： [1]Patent: WO2018/203235,2018,A1 .Location in patent: Page/Page column 17

20
[ 1073354-91-2 ]
N-(1-(6-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[4,3-b]pyridin-5-yl)-2-(3,5-difluorophenyl)ethyl)-2-methylpropane-2-sulfinamide [ No CAS ]
N-(1-(6-(benzo[d]thiazol-5-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[4,3-b]pyridin-5-yl)-2-(3,5-difluorophenyl)ethyl)-2-methylpropane-2-sulfinamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
150 mg	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In N,N-dimethyl-formamide; at 100℃; for 2h;Inert atmosphere;	A stirred solution of N-(l-(6-bromo-l-((2-(trimethylsilyl)ethoxy)methyl)- lH-pyrazolo[4,343]pyridin-5-yl)-2-(3,5-difluorophenyl)ethyl)-2-methylpropane-2- sulfinamide (mixture of diastereomers; 250 mg, 0.425 mmol) in DMF (5 mL) was degassed with nitrogen for 10 min. 5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2- yl)benzo[d]thiazole (133 mg, 0.511 mmol), 2CO3 (176 mg,1.276 mmol) were added followed by Pd(Pb.3P)4 (29.5 mg, 0.026 mmol) and the resulting solution was heated to 100 C and stirred for 2 h. The reaction mixture was cooled to RT, diluted with ethyl acetate (50 mL), washed with water (20 mL) and brine (20 mL), dried (Na2S04), filtered, and concentrated. The crude product was purified by Combiflash chromatography (12 g (0224) Redisep S1O2 column, eluting with 5% -20% EtOAc in hexanes) to afford title compound (150 mg). LC/MS: m/z = 642.4 [M+H]+. NMR (400 MHz, DMSO-c 6) delta ppm 9.64 (s, IH), 8.63 (d, J=1.00 Hz, IH), 8.43 (d, J=8.53 Hz, IH), 8.27 (d, J=1.00 Hz, IH), 8.0 (m, IH), 7.42 (m, IH), 7.08 (m, IH), 6.50 (d, J=6.0 Hz, 2H), 5.80 (s, 2H), 5.74 (d, J=8.53 Hz, IH), 4.92 (m, IH), 3.54 (t, J=8.03 Hz, 2H), 3.08 - 3.27 (m, 2H), 0.90 - 0.98 (m, 9H), 0.72 - 0.82 (m, 2H), -0.12 (m, 9H).

Reference： [1]Patent: WO2018/203235,2018,A1 .Location in patent: Page/Page column 36-37

21
[ 1073354-91-2 ]
tert-butyl (1-(6-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[4,3-b]pyridin-5-yl)-2-(3,5-difluorophenyl)ethyl)carbamate [ No CAS ]
tert-butyl (1-(6-(benzo[d]thiazol-5-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[4,3-b]pyridin-5-yl)-2-(3,5-difluorophenyl)ethyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
120 mg	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In N,N-dimethyl-formamide; at 100℃; for 2h;Inert atmosphere;	(0211) To a stirred solution of compound tert-butyl (l-(6-bromo-l-((2- (trimethylsilyl)ethoxy)methyl)-lH-pyrazolo[4,3-b]pyridin-5-yl)-2-(3,5- difluorophenyl)ethyl)carbamate(Int 4j, 150 mg, 0.257 mmol) in DMF (1 mL) was degassed with nitrogen for 10 min and then added 5-(4,4,5,5-tetramethyl-l,3,2- dioxaborolan-2-yl)benzo[d]thiazole (81 mg, 0.308 mmol), K2CO3 (107 mg, 0.77 mmol) followed by Pd(PhsP)4 (17.8 mg, 0.015 mmol) and the reaction mixture was heated to 100 C and stirred for 2 h. The reaction mixture was cooled to RT, diluted with ethyl acetate (50 mL), washed with water (20 mL) and brine (20 mL), dried (Na2S04), filtered, and concentrated. The crude product was purified by Combiflash chromatography (12 g Redisep S1O2 column, eluting with 5-20% EtOAc in hexanes) to afford the title product (120 mg). LC/MS: m/z = 638.2 [M+H]+. NMR (300 MHz, DMSO-cfc) delta ppm 9.51 (s, 1H), 8.46 (s, 1H), 8.32 (d, J=7.93 Hz, 1H), 8.12 (s, 1H), 8.07 (s, 1H), 7.53 (d, J=9.07 Hz, 1H), 7.32 (d, J=9.07 Hz, 1H), 6.85 - 6.97 (m, 1H), 6.37 (d, J=6.80 Hz, 2H), 5.81 (s, 2H), 4.99 - 5.10 (m, 1H), 3.55 (t, J=8.12 Hz, 2H), 2.94 (d, J=7.18 Hz, 2H), 1.23 (s, 9H), 0.77 - 0.86 (m, 2H), -0.12 (s, 9H).

Reference： [1]Patent: WO2018/203235,2018,A1 .Location in patent: Page/Page column 34

22
[ 64169-39-7 ]
[ 1073354-91-2 ]
3-[1-(4-fluorophenyl)-5-(1,3-benzothiazol-5-yl)-1,3-dihydro-2-benzofuran-1-yl]-N,N-dimethylpropan-1-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40%		In the same manner as Example 1, 250 mg (0.66 mmol, MW=378) of IV in 4.0 mL dioxane was treated with 38 mg (0.033 mmol, MW=1156) of (PPh3)4Pd(0) at room temp for 30 min, followed by the addition of 345 mg (1.32 mmol, MW=261.1; Combi-Blocks, INC., San Diego, Calif., USA) of <strong>[1073354-91-2]benzothiazole-5-boronic acid pinacol ester</strong> and 350 mg (3.3 mmol, MW=106) of Na2CO3 with 1.0 mL H2O. After heating at 80-85 C. under N2 for 4 hr, the dark red solution was extracted with EtOAc in a separatory funnel. The organic layer was washed with H2O and saturated NaCl, dried over MgSO4 and treated with Darco (activated charcoal). After filtration through a pad of d.e., the solvent was removed in vacuo to produce a crude oil. The oil was chromatographed on a silica gel plate (2000 micron, Analtech) and eluted with 90 EtOAc: 10 AcCN: 0.5 mL TEA. The silica gel band containing the product was scraped from the plate, stirred and extracted with EtOAc. The EtOAc was filtered and concentrated in vacuo to a crude oil. Yield of 70 mg (40%) as a viscous oil. Mass spectrum (m/z, %): Calcd. for C26H25FN2OS: M+=432.5. Found: 433 (M+1). NMR (400 MHz, CDCl3) delta 1.25 (s, 1H), 1.45 (bd, 2H), 2.00-2.35 (m, 9H), 5.25 (t, 2H), 7.0 (t, 2H), 7.25-7.55 (m, 7H), 8.0 (s, 1H), 8.35 (s, 1H), 9.0 (s, 1H).

Reference： [1]Patent: US2019/177304,2019,A1 .Location in patent: Paragraph 0186-0191

23
[ 1073354-91-2 ]
2-bromo-5,8-dihydro-4H-pyrazolo[1,5-a][1,3]diazepine-3-carboxamide [ No CAS ]
2-(benzo[d]thiazol-5-yl)-5,8-dihydro-4H-pyrazolo[1,5-a][1,3]diazepine-3-carboxamide [ No CAS ]