[ CAS No. 893441-86-6 ] {[proInfo.proName]}

Name: 893441-86-6|tert-Butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-1-carboxylate|95%
Brand: Ambeed
SKU: A196577
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Quality Control of [ 893441-86-6 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 893441-86-6 ]

Product Details of [ 893441-86-6 ]

CAS No. :	893441-86-6	MDL No. :	MFCD14155783
Formula :	C₁₉H₂₆BNO₄	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	FUXWYWGKVFEKQX-UHFFFAOYSA-N
M.W :	343.23	Pubchem ID :	60204498
Synonyms :

Calculated chemistry of [ 893441-86-6 ]

Physicochemical Properties

Num. heavy atoms :	25
Num. arom. heavy atoms :	9
Fraction Csp3 :	0.53
Num. rotatable bonds :	4
Num. H-bond acceptors :	4.0
Num. H-bond donors :	0.0
Molar Refractivity :	100.62
TPSA :	49.69 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	Yes
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	Yes
CYP3A4 inhibitor :	Yes
Log Kp (skin permeation) :	-5.37 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	4.26
Log Po/w (WLOGP) :	3.72
Log Po/w (MLOGP) :	2.43
Log Po/w (SILICOS-IT) :	2.16
Consensus Log Po/w :	2.52

Druglikeness

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

Water Solubility

Log S (ESOL) :	-4.65
Solubility :	0.00761 mg/ml ; 0.0000222 mol/l
Class :	Moderately soluble
Log S (Ali) :	-5.02
Solubility :	0.00331 mg/ml ; 0.00000965 mol/l
Class :	Moderately soluble
Log S (SILICOS-IT) :	-4.92
Solubility :	0.00411 mg/ml ; 0.000012 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	3.42

Safety of [ 893441-86-6 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 893441-86-6 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 893441-86-6 ]
Downstream synthetic route of [ 893441-86-6 ]

[ 893441-86-6 ] Synthesis Path-Upstream 1~3

1
[ 676448-17-2 ]
[ 73183-34-3 ]
[ 893441-86-6 ]

Yield	Reaction Conditions	Operation in experiment
75.8%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate In dimethyl sulfoxide at 80℃; for 12 h; Inert atmosphere	[0688] To a solution of fert-butyl 4-bromo-lH-indole-l -carboxylate (LXX) (9 g, 30 mmol) and bis(pinacolato)diboron (8.45 g, 33 mmol) in DMSO (180 mL) was added KOAc (9 g, 91 mmol). The suspension was purged with nitrogen (3x) before adding Pd(dppf)Cl2 (744 mg, 912 μιηο). The reaction was stirred at 80°C for 12 h. The suspension was poured into water (400 mL) and extracted with EtOAc (300 mL x 2). The combined organic layer was washed with brine (200 mL), dried over Na2S04 and concentrated under reduced pressure. Then the crude product was purified by silica gel (PE:EtOAc = 40: 1) to give fert-butyl 4-(4,4,5,5-tetramethyl-l,3,2- dioxaborolan-2-yl)-lH-indole-l-carboxylate (LXXXI) (7.8 g, 22.7 mmol, 75.8percent yield) as a white solid. NMR (CDCI₃, 400 MHz) δ ppm 1.38 (s, 12H), 1.68 (s, 9H), 7.09 (d, J=3.6Hz, IH), 7.30 (t, J=7.6Hz, IH), 7.61 (d, J=3.2Hz, IH), 7..70 (d, J=7.2Hz, IH), 8.24 (d, J=8Hz, IH); ESIMS found for C19H26BNO4 mlz 344.1 (M+H).
75.8%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate In dimethyl sulfoxide at 80℃; for 12 h; Inert atmosphere	To a solution of fert-butyl 4-bromo- lH-indole- 1 -carboxylate (LXXXVIII) (9 g, 30 mmol) and bis(pinacolato)diboron (8.45 g, 33 mmol) in DMSO (180 mL) was added KOAc (9 g, 91 mmol). The suspension was purged with nitrogen (3x) before adding Pd(dppf)Cl2 (744 mg, 912 μιηο). The reaction was stirred at 80°C for 12 h. The suspension was poured into water (400 mL) and extracted with EtOAc (300 mL x 2). The combined organic layer was washed with brine (200 mL), dried over Na2S04 and concentrated under reduced pressure . Then the crude product was purified by silica gel (PE:EtOAc = 40: 1) to give fert-butyl 4-(4,4,5,5-tetramethyl-l,3,2- dioxaborolan-2-yl)-lH-indole-l-carboxylate (XCVIII) (7.8 g, 22.7 mmol, 75.8percent yield) as a white solid. NMR (CDCI3, 400 MHz) δ ppm 1.38 (s, 12H), 1.68 (s, 9H), 7.09 (d, J=3.6Hz, IH), 7.30 (t, J=7.6Hz, IH), 7.61 (d, J=3.2Hz, IH), 7..70 (d, J=7.2Hz, IH), 8.24 (d, J=8Hz, IH); ESIMS found for C19H26BNO4 mlz 344.1 (M+H).
75.8%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate In dimethyl sulfoxide at 80℃; for 12 h; Inert atmosphere	To a solution of tert-butyl 4-bromo-1H-indole-1-carboxylate (LXX) (9 g, 30 mmol) and bis(pinacolato)diboron (8.45 g, 33 mmol) in DMSO (180 mL) was added KOAc (9 g, 91 mmol). The suspension was purged with nitrogen (3x) before adding Pd(dppf)Cl2 (744 mg, 912 μmol). The reaction was stirred at 80°C for 12 h. The suspension was poured into water (400 mL) and extracted with EtOAc (300 mL x 2). The combined organic layer was washed with brine (200 mL), dried over Na2SO4 and concentrated under reduced pressure. Then the crude product was purified by silica gel (PE:EtOAc = 40: 1) to give fert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-1-carboxylate (LXXXI) (7.8 g, 22.7 mmol, 75.8percent yield) as a white solid. 1H NMR (CDCl₃, 400 MHz) δ ppm 1.38 (s, 12H), 1.68 (s, 9H), 7.09 (d, J=3.6Hz, IH), 7.30 (t, J=7.6Hz, IH), 7.61 (d, J=3.2Hz, IH), 7..70 (d, J=7.2Hz, IH), 8.24 (d, J=8Hz, IH); ESIMS found for C19H26BNO4 m/z 344.1 (M+H).

75.8%

With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate In dimethyl sulfoxide at 80℃; for 12 h; Inert atmosphere

To a solution of tert-butyl 4-bromo-1H-indole-1-carboxylate (LXX) (9 g, 30 mmol) and bis(pinacolato)diboron (8.45 g, 33 mmol) in DMSO (180 mL) was added KOAc (9 g, 91 mmol). The suspension was purged with nitrogen (3x) before adding Pd(dppf)C12 (744 mg, 912 .imol). The reaction was stirred at 80°C for 12 h. The suspension was poured into water (400 mL) and extracted with EtOAc (300 mL x 2). The combined organic layer was washed with brine (200 mL), dried over Na2504 and concentrated under reduced pressure. Then the cmde product was purified by silica gel (PE:EtOAc = 40:1) to give tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)-1H-indole-1-carboxylate (LXXXI) (7.8 g, 22.7 mmol, 75.8percent yield) as a white solid. ‘HNMR(CDC13, 400 MHz) ppm 1.38 (s, 12H), 1.68 (s, 9H), 7.09 (d, J=3.6Hz, 1H), 7.30 (t,J=7.6Hz, 1H), 7.61 (d,J=3.2Hz, 1H), 7.70 (d,J=7.2Hz, 1H), 8.24 (d,J=8Hz, 1H); ESIMS found for C19H26BN04 mlz 344.1 (M+H).

Reference： [1] Patent: WO2017/23993, 2017, A1, . Location in patent: Paragraph 0687; 0688
[2] Patent: WO2017/23986, 2017, A1, . Location in patent: Paragraph 0705; 0706
[3] Patent: WO2017/23973, 2017, A1, . Location in patent: Paragraph 0704
[4] Patent: WO2017/24026, 2017, A1, . Location in patent: Paragraph 0686; 0687

2
[ 24424-99-5 ]
[ 893441-86-6 ]

Reference： [1] Patent: WO2017/23993, 2017, A1,
[2] Patent: WO2017/23986, 2017, A1,
[3] Patent: WO2017/23973, 2017, A1,
[4] Patent: WO2017/24026, 2017, A1,

3
[ 52488-36-5 ]
[ 893441-86-6 ]

Reference： [1] Patent: WO2017/23993, 2017, A1,
[2] Patent: WO2017/23986, 2017, A1,
[3] Patent: WO2017/23973, 2017, A1,
[4] Patent: WO2017/24026, 2017, A1,

[ 893441-86-6 ] Synthesis Path-Downstream 1~24

Yield	Reaction Conditions	Operation in experiment
77%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 85.0℃;Inert atmosphere;	General procedure: Step 34b: N-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetamide (Compound 0602-107)[0334]To a solution of compound 0601-107 (2.5 g, 11.6 mmol) and bis(pinacolato)diboron (4.4 g, 17.5 mmol) in dioxane (100 mL) was added potassium acetate (3.4 g, 35 mmol) and PdCl2(dppf)2 (0.95 g, 1.1 mmol). The mixture was degassed with nitrogen and heated at 85 C. for overnight. The reaction mixture was concentrated under reduced pressure to afford the crude product, which purified by column chromatography (ethyl acetate in petroleum ether, 15% v/v) to give the compound 0602-107 (1.55 g, 51%) as a pink solid. LCMS: 262 [M+1]+. 1H NMR (400 MHz, DMSO-d6) delta 1.29 (s, 12H), 2.03 (s, 3H), 7.30 (s, 1H), 7.31 (d, J=2.0 Hz 1H), 7.73 (d, J=2.0 Hz, 1H), 7.89 (d, J=1.6 Hz, 1H), 9.93 (s, 1H).
77%	With palladium bis[bis(diphenylphosphino)ferrocene] dichloride; potassium acetate; In 1,4-dioxane; at 85.0℃;Inert atmosphere;	General procedure: Compound in dioxane (100mL) 0601-107 (2.5g, 11.6mmol) and a solution of bis (pinacolato) diboron (4.4 g, 17.5 mmol), potassium acetate (3.4 g, 35 mmol) and and PdCl2 (dppf) 2 ( 0.95g, 1.1mmol) was added. The mixture was degassed with nitrogen and heated overnight at 85 C.. The reaction mixture was concentrated under reduced pressure to give the crude product, which was purified by column chromatography (petroleum ether in ethyl acetate, 15% v / v) to give the compound 0602-107 as a pink solid obtained (1.55 g, 51%).

2
[ 893441-86-6 ]
[ 1245464-68-9 ]
[ 1245465-28-4 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; water; for 2.0h;Inert atmosphere; Reflux;	To a round bottomed flask was charged 6-bromo-1-(phenylsulfonyl)-1 H-indazole-4- carbonitrile (10 g, 27.6 mmol), 1 ,1 -dimethylethyl 4-(4,4,5,5-tetramethyl-1 ,3,2- dioxaborolan-2-yl)-1 H-indole-1 -carboxylate (14.21 g, 41.4 mmol) and potassium phosphate tribasic (17.58 g, 83 mmol). The resulting mixture was treated with 1 ,4- dioxane (120 ml) and water (12 ml) that had previously been purged with nitrogen. The mixture was then treated with 1'-bis(diphenylphosphino)ferrocene palladium dichloride (1.547 g, 2.76 mmol) and heated to reflux, under nitrogen for 2 h. Additional 1'- bis(diphenylphosphino)ferrocene palladium dichloride (1.547 g, 2.76 mmol) was added and the mixture heated at reflux for a further 1 h. The hot reaction mixture was filtered through Celite, washed well with chloroform and the filtrate concentrated in vacuo. The residue was dissolved in DCM/cyclohexane (1 :1 , 50 ml) and purified by column chromatography on silica (75Og cartridge), eluting with 0-40% ethyl acetate/cyclohexane. The pure fractions were combined and concentrated to give the title compound as a yellow solid (6.16 g). LCMS (Method A): Rt 1.50 mins, MH+ 499.
6.16 g	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate; In 1,4-dioxane; water; for 3.0h;Inert atmosphere; Reflux;	The mixture was then treated with 1'-bis(diphenylphosphino)ferrocene palladium dichloride (1.547 g, 2.76 mmol) and heated to reflux, under nitrogen for 2 h. Additional 1'-bis(diphenylphosphino)ferrocene palladium dichloride (1.547 g, 2.76 mmol) was added and the mixture heated at reflux for a further 1 h. The hot reaction mixture was filtered through Celite, washed well with chloroform and the filtrate concentrated in vacuo. The residue was dissolved in DCM/cyclohexane (1:1, 50 ml) and purified by column chromatography on silica (750 g cartridge), eluting with 0-40% ethyl acetate/cyclohexane. The pure fractions were combined and concentrated to give the title compound as a yellow solid (6.16 g)._LCMS (Method A): Rt 1.50 mins, MH+ 499.

Reference： [1]Patent: WO2010/102958,2010,A1 .Location in patent: Page/Page column 108
[2]Patent: US9326987,2016,B2 .Location in patent: Page/Page column 104; 105

3
[ 893441-86-6 ]
[ 1245465-37-5 ]
[ 1245465-99-9 ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate; In 1,4-dioxane; water; at 100.0℃; for 0.333333h;Microwave irradiation;	6-l3romo-4-{5-[(2-methyl-4-morpholinyl)methyl]-1 ,3,4- oxadiazol-2-yl}- 1 -(phenylsulfonyl)- 1H-indazole (269 mg,0.519 mmol) was dissolved in 1 ,4-dioxane (5 ml) and half of this stock solution was charged to a reaction vessel. 4-(4,4,5, 5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-1 H-indole (82 mg,0.337 mmol), 1,1 ?-bis(diphenylphosphino)ferrocene palladium dichloride (38 mg, 0.052 mmol), potassium phosphatetribasic (165 mg, 0.779 mmol) and water (0.25 ml) were added. The reaction mixture was heated under microwave irradiation at 1000 C. for 20 mins. The mixture was passed through a 1 g silica SPE cartridge, washing with MeOR. The solvent was removed under a stream of nitrogen and theresidue was partitioned between DCM (10 ml) and water (10 ml), separated with a hydrophobic frit and the solvent again removed under a stream of nitrogen. The crude residue was purified using preparative HPLC as follows:The appropriate fractions were dried down. 1 ,4-Dioxane (1 ml) and 2M sodium hydroxide (1 ml, 2.000 mmol) was added and the mixture stirred at 20 C. for 2 h. The mixture was partitioned between ethyl acetate (5 ml) and saturated ammo5 nium chloride solution (2 ml), separating the layers with ahydrophilic frit. The organic layer was evaporated to dryness under a stream of nitrogen. The residue was taken up again in 1,4-dioxane (1 ml) and 2M sodium hydroxide (1 ml, 2.000 mmol) and stirred at room temperature for 3 h. The mixturewas evaporated under a stream of nitrogen. The residue was partitioned between ethyl acetate and saturated ammonium chloride solution, the organic layer was separated with a hydrophilic frit and the solvent removed under a stream ofnitrogen to give the title compound as a cream solid (18 mg).LCMS (Method A): Rt 0.75 mins, MH+ 415.

Reference： [1]Patent: US9326987,2016,B2 .Location in patent: Page/Page column 201; 202

4
[ 893441-86-6 ]
[ 1245465-37-5 ]
[ 1245464-40-7 ]

Reference： [1]Patent: US9326987,2016,B2

5
[ 893441-86-6 ]
[ 1235450-25-5 ]
[ 1235451-61-2 ]

Yield	Reaction Conditions	Operation in experiment
59%	With palladium bis[bis(diphenylphosphino)ferrocene] dichloride; caesium carbonate; In 1,4-dioxane; water; at 120.0℃; for 1.0h;Inert atmosphere; Microwave irradiation;	In toluene (4 mL), ethanol (2 mL) and water (1 mL), compound 0504-83 (300mg, 0.6mmol), 0107-3 (176mg, 0.72mmol), NaHCO3 (152mg, 1.8mmol) and bis (triphenyl sprayed with nitrogen to the mixture of phosphine) palladium (II) (22mg, 0.03mmol), was heated under microwave irradiation for 1 hour at 120. C.. The reaction mixture was partitioned between dichloromethane and water, the organic layer was washed with brine, dried over Na2SO4, filtered and evaporated in vacuo. The resulting residue was obtained and purified using column chromatography (dichloromethane with methanol, 2-5% v / v), the title compound 0505-83 (300mg, 85%) as a white solid. 1,4-dioxane (6mL) and in water (0.2mL) 0504-54 (448mg1.00mmol)0602-176 (343mg1.00mmol) Cs2CO3(652mg 2.00mmol) and Pd (dppf) 2Cl2 (82mg, 0.10mmol), , Using a procedure similar to that described for compound 0603-107 (Example 34), compound tert- butyl 4- (6 - (((5- (ethoxycarbonyl) pyrimidin-2-yl) (methyl ) amino) methyl) -4- morpholinothieno [3,2-d] pyrimidin-2-yl)-lH-indole-1-carboxylate whiteIt was prepared as a solid (368mg, 59%).

Reference： [1]Patent: JP2015/187145,2015,A .Location in patent: Paragraph 0259; 0477

6
[ 893441-86-6 ]
(1-(tert-butoxycarbonyl)-4-(pyridin-2-yl)-1H-indol-2-yl)boronic acid [ No CAS ]

Reference： [1]Patent: WO2017/23993,2017,A1
[2]Patent: WO2017/23986,2017,A1
[3]Patent: WO2017/23973,2017,A1
[4]Patent: WO2017/24026,2017,A1

7
[ 109-04-6 ]
[ 893441-86-6 ]
tert-butyl 4-(pyridin-2-yl)-1H-indole-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84.9%	With tetrakis(triphenylphosphine) palladium(0); sodium hydroxide; In tetrahydrofuran; water; at 70.0℃; for 6.0h;Inert atmosphere;	A solution of fert-butyl 4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH- indole- 1-carboxylate (LXXXI) (4.8 g, 14 mmol) and 2-bromopyridine (LXXXII) (2.6 g, 17 mmol) in THF (70 mL) was added aqueous NaOH (2.24 g, 56 mmol) in water (30 mL). The suspension was purged with nitrogen (3x) before adding Pd(PPli3)4 (485 mg, 420 mupiiotaomicron). The reaction was heated to 70C and stirred for 6 h. The suspension was poured into water (80 mL) and extracted with EtOAc (250 mL x 2). The combined organic layer was washed with brine ( 100 mL), dried over Na2SC>4 and concentrated under reduced pressure. The crude product was purified by silica gel (PE:EtOAc = 30: 1) to give fert-butyl 4-(pyridin-2-yl)-lH-indole-l-carboxylate (LXXXIII) (3.5 g, 11.9 mmol, 84.9% yield) as a yellow oil. NMR (CDC13, 400 MHz) delta ppm 1.69 (s, 9H), 7.29 (d, J=7.6Hz, 2H), 7.42 (t, J=7.6Hz, IH), 7.62 (d, J=7.2Hz, IH), 7.67 (d, J=3.6Hz, IH), 7.74 (d, J=8Hz, IH), 7.82 (t, J=8Hz, IH), 8.26 (d, J=8.4Hz, IH), 8.78 (d, J=4.8Hz, IH); ESIMS found for CigHigNzOz mlz 295.1 (M+H).
84.9%	With tetrakis(triphenylphosphine) palladium(0); sodium hydroxide; In tetrahydrofuran; water; at 70.0℃; for 6.0h;Inert atmosphere;	A solution of fert-butyl 4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH- indole-1 -carboxylate (XCVIII) (4.8 g, 14 mmol) and 2-bromopyridine (XCIX) (2.6 g, 17 mmol) in THF (70 mL) was added aqueous NaOH (2.24 g, 56 mmol) in water (30 mL). The suspension was purged with nitrogen (3x) before adding Pd(PPli3)4 (485 mg, 420 mupiiotaomicron). The reaction was heated to 70C and stirred for 6 h. The suspension was poured into water (80 mL) and extracted with EtOAc (250 mL x 2). The combined organic layer was washed with brine (100 mL), dried over Na2S04 and concentrated under reduced pressure. The crude product was purified by silica gel (PE:EtOAc = 30: 1) to give tert-butyl 4-(pyridin-2-yl)-lH-indole-l -carboxylate (C) (3.5 g, 11.9 mmol, 84.9% yield) as a yellow oil. NMR (CDC13, 400 MHz) delta ppm 1.69 (s, 9H), 7.29 (d, J=7.6Hz, 2H), 7.42 (t, J=7.6Hz, IH), 7.62 (d, J=7.2Hz, IH), 7.67 (d, J=3.6Hz, IH), 7.74 (d, J=8Hz, IH), 7.82 (t, J=8Hz, IH), 8.26 (d, J=8.4Hz, IH), 8.78 (d, J=4.8Hz, IH); ESIMS found for CigHigNzOz mlz 295.1 (M+H).
84.9%	With tetrakis(triphenylphosphine) palladium(0); sodium hydroxide; In tetrahydrofuran; water; at 70.0℃; for 6.0h;Inert atmosphere;	A solution of <strong>[893441-86-6]tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-1-carboxylate</strong> (LXXXI) (4.8 g, 14 mmol) and 2-bromopyridine (LXXXII) (2.6 g, 17 mmol) in THF (70 mL) was added aqueous NaOH (2.24 g, 56 mmol) in water (30 mL). The suspension was purged with nitrogen (3x) before adding Pd(PPh3)4 (485 mg, 420 mupiiotaomicron). The reaction was heated to 70C and stirred for 6 h. The suspension was poured into water (80 mL) and extracted with EtOAc (250 mL x 2). The combined organic layer was washed with brine (100 mL), dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel (PE:EtOAc = 30: 1) to give tert-butyl 4-(pyridin-2-yl)-1H-indole-1-carboxylate (LXXXIII) (3.5 g, 11.9 mmol, 84.9% yield) as a yellow oil. 1H NMR (CDCI3, 400 MHz) delta ppm 1.69 (s, 9H), 7.29 (d, J=7.6Hz, 2H), 7.42 (t, J=7.6Hz, IH), 7.62 (d, J=7.2Hz, IH), 7.67 (d, J=3.6Hz, IH), 7.74 (d, J=8Hz, IH), 7.82 (t, J=8Hz, IH), 8.26 (d, J=8.4Hz, IH), 8.78 (d, J=4.8Hz, IH); ESIMS found for C18H18N2O2 m/z 295.1 (M+H).

84.9%

With tetrakis(triphenylphosphine) palladium(0); sodium hydroxide; In tetrahydrofuran; water; at 70.0℃; for 6.0h;

A solution of tert-butyl 4-(4,4,5 ,5 -tetramethyl- 1,3 ,2-dioxaborolan-2-yl)- 1H- indole-1-carboxylate (LXXXI) (4.8 g, 14 mmol) and 2-bromopyridine (LXXXII) (2.6 g, 17 mmol) in THF (70 mL) was added aqueous NaOH (2.24 g, 56 mmol) in water (30 mL). The suspension was purged with nitrogen (3x) before adding Pd(PPh3)4 (485 mg, 420 .imol). The reaction was heated to 70C and stirred for 6 h. The suspension was poured into water (80 mL) and extracted with EtOAc (250 mL x 2). The combined organic layer was washed with brine (100 mL), dried over Na2504 and concentrated under reduced pressure. The cmde product was purified by silica gel (PE:EtOAc = 30:1) to give tert-butyl 4-(pyridin-2-yl)-1H-indole-1-carboxylate (LXXXIII) (3.5 g, 11.9 mmol, 84.9% yield) as a yellow oil. ?H NMR (CDC13, 400 MHz) ppm 1.69 (s, 9H), 7.29 (d, J7.6Hz, 2H), 7.42 (t, J7.6Hz, 1H), 7.62 (d, J7.2Hz, 1H), 7.67 (d, J3.6Hz, 1H), 7.74 (d, J=8Hz, 1H), 7.82 (t, J=8Hz, 1H), 8.26 (d, J8.4Hz, 1H), 8.78 (d, J4.8Hz, 1H); ESIMS found for C,8H,8N202 mlz 295.1 (M+H).

Reference： [1]Patent: WO2017/23993,2017,A1 .Location in patent: Paragraph 0687; 0689
[2]Patent: WO2017/23986,2017,A1 .Location in patent: Paragraph 0705; 0707
[3]Patent: WO2017/23973,2017,A1 .Location in patent: Paragraph 0705
[4]Patent: WO2017/24026,2017,A1 .Location in patent: Paragraph 0686; 0688

8
[ 24424-99-5 ]
[ 893441-86-6 ]

Reference： [1]Patent: WO2017/23993,2017,A1
[2]Patent: WO2017/23986,2017,A1
[3]Patent: WO2017/23973,2017,A1
[4]Patent: WO2017/24026,2017,A1

9
[ 676448-17-2 ]
[ 73183-34-3 ]
[ 893441-86-6 ]

Yield	Reaction Conditions	Operation in experiment
75.8%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In dimethyl sulfoxide; at 80℃; for 12h;Inert atmosphere;	[0688] To a solution of fert-butyl 4-bromo-lH-indole-l -carboxylate (LXX) (9 g, 30 mmol) and bis(pinacolato)diboron (8.45 g, 33 mmol) in DMSO (180 mL) was added KOAc (9 g, 91 mmol). The suspension was purged with nitrogen (3x) before adding Pd(dppf)Cl2 (744 mg, 912 muiotaetaomicron). The reaction was stirred at 80C for 12 h. The suspension was poured into water (400 mL) and extracted with EtOAc (300 mL x 2). The combined organic layer was washed with brine (200 mL), dried over Na2S04 and concentrated under reduced pressure. Then the crude product was purified by silica gel (PE:EtOAc = 40: 1) to give fert-butyl 4-(4,4,5,5-tetramethyl-l,3,2- dioxaborolan-2-yl)-lH-indole-l-carboxylate (LXXXI) (7.8 g, 22.7 mmol, 75.8% yield) as a white solid. NMR (CDCI3, 400 MHz) delta ppm 1.38 (s, 12H), 1.68 (s, 9H), 7.09 (d, J=3.6Hz, IH), 7.30 (t, J=7.6Hz, IH), 7.61 (d, J=3.2Hz, IH), 7..70 (d, J=7.2Hz, IH), 8.24 (d, J=8Hz, IH); ESIMS found for C19H26BNO4 mlz 344.1 (M+H).
75.8%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In dimethyl sulfoxide; at 80℃; for 12h;Inert atmosphere;	To a solution of fert-butyl 4-bromo- lH-indole- 1 -carboxylate (LXXXVIII) (9 g, 30 mmol) and bis(pinacolato)diboron (8.45 g, 33 mmol) in DMSO (180 mL) was added KOAc (9 g, 91 mmol). The suspension was purged with nitrogen (3x) before adding Pd(dppf)Cl2 (744 mg, 912 muiotaetaomicron). The reaction was stirred at 80C for 12 h. The suspension was poured into water (400 mL) and extracted with EtOAc (300 mL x 2). The combined organic layer was washed with brine (200 mL), dried over Na2S04 and concentrated under reduced pressure . Then the crude product was purified by silica gel (PE:EtOAc = 40: 1) to give fert-butyl 4-(4,4,5,5-tetramethyl-l,3,2- dioxaborolan-2-yl)-lH-indole-l-carboxylate (XCVIII) (7.8 g, 22.7 mmol, 75.8% yield) as a white solid. NMR (CDCI3, 400 MHz) delta ppm 1.38 (s, 12H), 1.68 (s, 9H), 7.09 (d, J=3.6Hz, IH), 7.30 (t, J=7.6Hz, IH), 7.61 (d, J=3.2Hz, IH), 7..70 (d, J=7.2Hz, IH), 8.24 (d, J=8Hz, IH); ESIMS found for C19H26BNO4 mlz 344.1 (M+H).
75.8%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In dimethyl sulfoxide; at 80℃; for 12h;Inert atmosphere;	To a solution of <strong>[676448-17-2]tert-butyl 4-bromo-1H-indole-1-carboxylate</strong> (LXX) (9 g, 30 mmol) and bis(pinacolato)diboron (8.45 g, 33 mmol) in DMSO (180 mL) was added KOAc (9 g, 91 mmol). The suspension was purged with nitrogen (3x) before adding Pd(dppf)Cl2 (744 mg, 912 mumol). The reaction was stirred at 80C for 12 h. The suspension was poured into water (400 mL) and extracted with EtOAc (300 mL x 2). The combined organic layer was washed with brine (200 mL), dried over Na2SO4 and concentrated under reduced pressure. Then the crude product was purified by silica gel (PE:EtOAc = 40: 1) to give fert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-1-carboxylate (LXXXI) (7.8 g, 22.7 mmol, 75.8% yield) as a white solid. 1H NMR (CDCl3, 400 MHz) delta ppm 1.38 (s, 12H), 1.68 (s, 9H), 7.09 (d, J=3.6Hz, IH), 7.30 (t, J=7.6Hz, IH), 7.61 (d, J=3.2Hz, IH), 7..70 (d, J=7.2Hz, IH), 8.24 (d, J=8Hz, IH); ESIMS found for C19H26BNO4 m/z 344.1 (M+H).

75.8%

With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In dimethyl sulfoxide; at 80℃; for 12h;Inert atmosphere;

To a solution of <strong>[676448-17-2]tert-butyl 4-bromo-1H-indole-1-carboxylate</strong> (LXX) (9 g, 30 mmol) and bis(pinacolato)diboron (8.45 g, 33 mmol) in DMSO (180 mL) was added KOAc (9 g, 91 mmol). The suspension was purged with nitrogen (3x) before adding Pd(dppf)C12 (744 mg, 912 .imol). The reaction was stirred at 80C for 12 h. The suspension was poured into water (400 mL) and extracted with EtOAc (300 mL x 2). The combined organic layer was washed with brine (200 mL), dried over Na2504 and concentrated under reduced pressure. Then the cmde product was purified by silica gel (PE:EtOAc = 40:1) to give tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)-1H-indole-1-carboxylate (LXXXI) (7.8 g, 22.7 mmol, 75.8% yield) as a white solid. ?HNMR(CDC13, 400 MHz) ppm 1.38 (s, 12H), 1.68 (s, 9H), 7.09 (d, J=3.6Hz, 1H), 7.30 (t,J=7.6Hz, 1H), 7.61 (d,J=3.2Hz, 1H), 7.70 (d,J=7.2Hz, 1H), 8.24 (d,J=8Hz, 1H); ESIMS found for C19H26BN04 mlz 344.1 (M+H).

Reference： [1]Patent: WO2017/23993,2017,A1 .Location in patent: Paragraph 0687; 0688
[2]Patent: WO2017/23986,2017,A1 .Location in patent: Paragraph 0705; 0706
[3]Patent: WO2017/23973,2017,A1 .Location in patent: Paragraph 0704
[4]Patent: WO2017/24026,2017,A1 .Location in patent: Paragraph 0686; 0687

10
[ 52488-36-5 ]
[ 893441-86-6 ]

Reference： [1]Patent: WO2017/23993,2017,A1
[2]Patent: WO2017/23986,2017,A1
[3]Patent: WO2017/23973,2017,A1
[4]Patent: WO2017/24026,2017,A1

11
[ 893441-86-6 ]
tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)octahydro-1H-indole-1-carboxylate [ No CAS ]
tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)octahydro-1H-indole-1-carboxylate [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2019,vol. 58,p. 6554 - 6558
Angew. Chem.,2019,vol. 131,p. 6626 - 6630,5

12
[ 76-09-5 ]
(1-(tert-butoxycarbonyl)-1H-indol-4-yl)boronic acid [ No CAS ]
[ 893441-86-6 ]

Reference： [1]Angewandte Chemie - International Edition,2019,vol. 58,p. 6554 - 6558
Angew. Chem.,2019,vol. 131,p. 6626 - 6630,5

13
[ 893441-86-6 ]
[ 5471-81-8 ]
[ 80-48-8 ]
tert-butyl 4-(4-(methoxycarbonyl)-2,6-dimethylphenyl)-1H-indole-1-carboxylate [ No CAS ]