[ CAS No. 642494-37-9 ]

Name: 642494-37-9|7-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole|97%
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SKU: A217937
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Quality Control of [ 642494-37-9 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 642494-37-9 ]

Product Details of [ 642494-37-9 ]

CAS No. :	642494-37-9	MDL No. :	MFCD08669591
Formula :	C₁₄H₁₈BNO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	QAXZRSICOHKXML-UHFFFAOYSA-N
M.W :	243.11	Pubchem ID :	11265016
Synonyms :

Calculated chemistry of [ 642494-37-9 ]

Physicochemical Properties

Num. heavy atoms :	18
Num. arom. heavy atoms :	9
Fraction Csp3 :	0.43
Num. rotatable bonds :	1
Num. H-bond acceptors :	2.0
Num. H-bond donors :	1.0
Molar Refractivity :	74.77
TPSA :	34.25 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) :	-5.62 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	3.04
Log Po/w (WLOGP) :	2.47
Log Po/w (MLOGP) :	1.49
Log Po/w (SILICOS-IT) :	2.42
Consensus Log Po/w :	1.88

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.57
Solubility :	0.066 mg/ml ; 0.000271 mol/l
Class :	Soluble
Log S (Ali) :	-3.43
Solubility :	0.0914 mg/ml ; 0.000376 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-4.89
Solubility :	0.00314 mg/ml ; 0.0000129 mol/l
Class :	Moderately soluble

Medicinal Chemistry

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

Safety of [ 642494-37-9 ]

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

Application In Synthesis of [ 642494-37-9 ]

* 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 [ 642494-37-9 ]
Downstream synthetic route of [ 642494-37-9 ]

[ 642494-37-9 ] Synthesis Path-Upstream 1~9

1
[ 51417-51-7 ]
[ 73183-34-3 ]
[ 642494-37-9 ]

Yield	Reaction Conditions	Operation in experiment
25 g	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate In dimethyl sulfoxide at 85℃; for 2 h;	7-bromoindole (20 g, 0.102mol) was dissolved in DMSO (100mL) in an 1 L single neck flask, and bis(pinacolato)diboron (39 g, 0.153 mol), [1,1’-bis(diphenylphosphino)ferrocene]dichloropalladium (Pd(dppf)Cl2, 4 g, 0.005 mol),and potassium acetate (15 g, 0.153 mol) were added. The system was heated to 85 °C to react for 2 h. Water was addedto quench the reaction. The mixture was extracted with ethyl acetate for 3 times, dried over sodium sulfate, concentrated,and subjected to column chromatography to obtain the product (25 g, 0.103 mol). 1H NMR (400 MHz, CDCl3): δ 9.29(s, 1H), 7.82 (d, J = 7.9 Hz, 1H), 7.70 (d, J = 7.0 Hz, 1H), 7.32-7.29 (m, 1H), 7.21-7.14 (m, 1H), 6.62-6.57 (m, 1H), 1.44(s, 12H). MS (ESI) (m/z): [M+H]+ 244.1.

Reference： [1] Synlett, 2003, # 8, p. 1204 - 1206
[2] Advanced Synthesis and Catalysis, 2017, vol. 359, # 19, p. 3421 - 3427
[3] Journal of the American Chemical Society, 2017, vol. 139, # 24, p. 8267 - 8276
[4] European Journal of Organic Chemistry, 2016, vol. 2016, # 27, p. 4621 - 4628
[5] Patent: JP2015/528445, 2015, A, . Location in patent: Paragraph 0047; 0065
[6] Patent: EP3345906, 2018, A1, . Location in patent: Paragraph 0332; 0333

2
[ 51417-51-7 ]
[ 25015-63-8 ]
[ 642494-37-9 ]

Reference： [1] Journal of Organic Chemistry, 2006, vol. 71, # 15, p. 5807 - 5810
[2] Patent: WO2006/10142, 2006, A2, . Location in patent: Page/Page column 83; 84

3
[ 120-72-9 ]
[ 73183-34-3 ]
[ 25015-63-8 ]
[ 642494-37-9 ]

Reference： [1] European Journal of Organic Chemistry, 2017, vol. 2017, # 27, p. 4044 - 4053

4
[ 116491-57-7 ]
[ 642494-37-9 ]

Reference： [1] Journal of the American Chemical Society, 2006, vol. 128, # 49, p. 15552 - 15553

5
[ 25015-63-8 ]
[ 642494-37-9 ]

Reference： [1] Journal of the American Chemical Society, 2006, vol. 128, # 49, p. 15552 - 15553

6
[ 51417-51-7 ]
[ 642494-37-9 ]

Reference： [1] Heterocycles, 2010, vol. 80, # 2, p. 1267 - 1274
[2] Patent: US2015/318483, 2015, A1,

7
[ 73183-34-3 ]
[ 25015-63-8 ]
[ 642494-37-9 ]

Reference： [1] Journal of the American Chemical Society, 2010, vol. 132, # 12, p. 4068 - 4069

8
[ 73183-34-3 ]
[ 642494-37-9 ]

Reference： [1] Organic Letters, 2016, vol. 18, # 7, p. 1554 - 1557

9
[ 120-72-9 ]
[ 642494-37-9 ]

Reference： [1] Organic Letters, 2016, vol. 18, # 7, p. 1554 - 1557

[ 642494-37-9 ] Synthesis Path-Downstream 1~68

1
[ 51417-51-7 ]
[ 73183-34-3 ]
[ 642494-37-9 ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In N,N-dimethyl-formamide; at 130℃; for 12h;Inert atmosphere;	General procedure: Under a nitrogen stream, 5-bromo-1H-indole (25g, 0.128mol), 4,4,4?,4?,5,5,5?,5?-octamethyl-2,2?-bi(1,3,2-dioxaborolane)(48.58g, 0.191mol), Pd (dppf) Cl2 (5.2g, 5mol), KOAc (37.55g, 0.383mol), and 1,4-dioxane (500ml) mixed, and the mixture was stirred for 12 hours at 130C .After completion of the reaction, and extracted with ethyl acetate, water was removed by MgSO4, column chromatography (hexane: EA = 10: 1 (v / v)) purified to at 5- (4,4,5,5-tetra to give methyl 1,3,2-dioxaborolan-2-yl)-lH-indole (22.32g, 72% yield).7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indolewas obtained by performing the same procedure as in ofPreparation Example 1, except that 7-bromo-1H-indole was used insteadof 5-bromo-1H-indole.
25 g	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In dimethyl sulfoxide; at 85℃; for 2h;	7-bromoindole (20 g, 0.102mol) was dissolved in DMSO (100mL) in an 1 L single neck flask, and bis(pinacolato)diboron (39 g, 0.153 mol), [1,1?-bis(diphenylphosphino)ferrocene]dichloropalladium (Pd(dppf)Cl2, 4 g, 0.005 mol),and potassium acetate (15 g, 0.153 mol) were added. The system was heated to 85 C to react for 2 h. Water was addedto quench the reaction. The mixture was extracted with ethyl acetate for 3 times, dried over sodium sulfate, concentrated,and subjected to column chromatography to obtain the product (25 g, 0.103 mol). 1H NMR (400 MHz, CDCl3): delta 9.29(s, 1H), 7.82 (d, J = 7.9 Hz, 1H), 7.70 (d, J = 7.0 Hz, 1H), 7.32-7.29 (m, 1H), 7.21-7.14 (m, 1H), 6.62-6.57 (m, 1H), 1.44(s, 12H). MS (ESI) (m/z): [M+H]+ 244.1.

Reference： [1]Synlett,2003,p. 1204 - 1206
[2]Advanced Synthesis and Catalysis,2017,vol. 359,p. 3421 - 3427
[3]Journal of the American Chemical Society,2017,vol. 139,p. 8267 - 8276
[4]European Journal of Organic Chemistry,2016,vol. 2016,p. 4621 - 4628
[5]Patent: JP2015/528445,2015,A .Location in patent: Paragraph 0047; 0065
[6]Patent: EP3345906,2018,A1 .Location in patent: Paragraph 0332; 0333

2
[ 51417-51-7 ]
[ 25015-63-8 ]
[ 642494-37-9 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; at 100℃; for 18h;	This compound was prepared by combining a mixture of 7-bromoindole (5.9 g), Pd(dppf)Cl2 dichloromethane complex (0.98 g, 1.2 mmol) in a flask and flushing the flask with nitrogen. Then dioxane (140 mL), triethylamine (14.6 mL), and pinacolborane (8.0 mL) is added. The reaction is heated at 100 C for 18 h. The reaction is quenched with saturated ammonium chloride, and the mixture is extracted with EtOAc (2 x 250 mL). The organic layers is washed with brine, dried over magnesium sulfate, filtered, and concentrated. Flash chromatography (15% EtOAc/hexanes) affords 7-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)indole (5.5 g).

Reference： [1]Journal of Organic Chemistry,2006,vol. 71,p. 5807 - 5810
[2]Patent: WO2006/10142,2006,A2 .Location in patent: Page/Page column 83; 84

3
7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-trimethylsilanylindole [ No CAS ]
[ 642494-37-9 ]

Reference： [1]Journal of the American Chemical Society,2006,vol. 128,p. 15552 - 15553

4
[ 5750-76-5 ]
[ 642494-37-9 ]
C₁₂H₇Cl₂N₃ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 2179 - 2183

5
[ 642494-37-9 ]
C₂₂H₂₂ClN₅ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 2179 - 2183

6
[ 116491-57-7 ]
[ 642494-37-9 ]

Reference： [1]Journal of the American Chemical Society,2006,vol. 128,p. 15552 - 15553

7
[ 25015-63-8 ]
[ 642494-37-9 ]

Reference： [1]Journal of the American Chemical Society,2006,vol. 128,p. 15552 - 15553

Yield	Reaction Conditions	Operation in experiment
87%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 130℃; for 12h;Inert atmosphere;	General procedure: Under the nitrogen air 5-bromo-1H-indole (25 g, 0.128 mol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane) (48.58 g, 0.191 mol), pd(dppf)Cl2 (5.2 g, 5 mol), KOAc (37.55 g, 0.383 mol) and 1,4-dioxane (500 ml) were mixed, then it was stirred at 130 C for 12 hours. After reaction being terminated, then ethyl acetate extraction of MgSO 4 for removing moisture to, column chromatography ( reaction is concluded Hexane: it was refined to the EA = 10:1 (v/v)) for purifying the 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (22.32 g, yield 72%) were obtained.
		<Step 1> Synthesis of 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole was obtained by performing the same procedure as in <Step 1> of Preparation Example 1, except that 7-bromo-1H-indole was used instead of 6-bromo-1H-indole. 1H-NMR: delta 1.25 (s, 12H), 6.43 (d, 1H), 7.25 (d, 1H), 7.45 (t, 1H), 7.56 (d, 1H), 7.71 (d, 1H), 8.22 (s, 1H)
		<Step 1> Synthesis of 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole was obtained by performing the same procedure as in <Step 1> of Preparation Example 1, except that 7-bromo-1H-indole was used instead of 5-bromo-1H-indole. 1H-NMR: delta 1.25 (s, 12H), 6.43 (d, 1H), 7.25 (d, 1H), 7.45 (t, 1H), 7.56 (d, 1H), 7.71 (d, 1H), 8.22 (s, 1H)

	With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); potassium acetate; In 1,4-dioxane; at 130℃; for 12h;Inert atmosphere;	General procedure: Under a nitrogen flow 5-bromo-1H-indole (25 g, 0.128 mol), 4,4,4 ', 4', 5,5, 5 ', 5'-octamethyl-2,2'-bi (1,3 ,2-dioxaborolane) (48.58 g, 0.191 mol), Pd (dppf) Cl2 (5.2 g, 5 mol), KOAc (37.55g, 0.383mol) and 1,4-dioxane (500 ml) the mixture, and then the 130 in it was stirred for 12 hours.After the reaction was completed, the removal of water in our MgSO4 and then extracted with ethyl acetate, column chromatography (Hexane: ethyl acetate (EA) = 10: 1 (v / v)) to give 5- (4,4,5 a , 5-tetramethyl-1,3,2-dioxaborolan-2-yl) -1H-indole (22.32 g, a yield of 72%).
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In N,N-dimethyl-formamide; at 130℃; for 12h;Inert atmosphere;	General procedure: Under a nitrogen stream, 5-bromo-1H-indole (25g, 0.128mol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi-(1,3,2-dioxaborolane) (48.58g, 0.191mol), Pd(dppf)Cl2 (5.2g, 5mol), KOAc (37.55g, 0.383mol) and a mixture of DMF (500ml), 12 hours with stirring at 130 C. After completion of the reaction, and extracted with ethyl acetate, to remove water with MgSO4, is purified by Karamukuro Matogurafi (Hexane: EA = 10: 1 (v / v)) was obtained 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl)-1H-indole (12.43g, 40% yield).
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 130℃; for 12h;Inert atmosphere;	General procedure: Under a nitrogen flow 5-bromo-1H-indole (25 g, 0.128 mol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane) (48.58 g, 0.191 mol), Pd(dppf)Cl2 (5.2 g, 5 mol), KOAc (37.55 g, 0.383 mol) and 1,4-dioxane (500 ml) and the mixture at 130C , It was stirred for 12 hours. After the reaction was terminated by the removal of water and then extracted with ethyl acetate and MgSO4, purified by column chromatography (Hexane: EA = 10: 1 (v / v)) 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (22.32 g, a yield of 72%).
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In N,N-dimethyl-formamide; at 130℃; for 12h;Inert atmosphere;	General procedure: Under a nitrogen stream, 6-bromo -1H- indole (25g, 0.128mol), 4,4,4 ', 4', 5,5,5 ', 5'- octamethyl-2,2'-bi (1, 3,2-dioxaborolane) (48.58g, 0.191mol), Pd (dppf) Cl2 (5.2g, 5mol%), were mixed KOAc (37.55g, 0.383mol) and DMF with (500ml), 130 the mixture was stirred for 12 hours at . After completion of the reaction, and extracted with ethyl acetate, water was removed by MgSO4, column chromatography (hexane: EA = 10: 1 (v / v)) was purified by 6-4,4,5,5- tetramethyl to give the 1,3,2-dioxaborolan-2-yl)-lH-indole (20.15g, 65% yield).
	With palladium bis[bis(diphenylphosphino)ferrocene] dichloride; potassium acetate; In N,N-dimethyl-formamide; at 130℃; for 12h;Inert atmosphere;	General procedure: 5-bromo-1H-indole (25 g, 0.128 mol) was added under a nitrogen stream, 4,4,4 ', 4', 5,5,5 ', 5'-octamethyl-2,2'-bi (1,3,2-dioxaborolane)(48.58 g, 0.191 mol), Pd (dppf) Cl2 (5.2 g, 5 mol), KOAc (37.55 g, 0.383 mol) andWere mixed DMF (500 ml) And the mixture was stirred at 130 DEG C for 12 hours.After the reaction was completed, the reaction mixture was extracted with ethyl acetate, the water was removed with MgSO4,Purification by column chromatography (Hexane: EA = 10: 1 (v / v)) gave5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -1H-indole(12.43 g, yield 40%).

9
[ 494799-19-8 ]
[ 642494-37-9 ]
[ 1169856-70-5 ]

Yield	Reaction Conditions	Operation in experiment
99%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In methanol; water; N,N-dimethyl-formamide; at 130℃; for 0.25h;Microwave;	2-Bromo-3-cyclohexyl-lH-indole-6-carboxylic acid methyl ester (Ig, 2.98 mmole), 7-(4,4,5,5-Tetramethyl-[l,3,2]dioxaborolan-2-yl)-lH-indole (1.46g, 5.96 mmole, 2eq), and tetrakis(triphenylphophine)palladium(0) (332mg, 0.298mmole, O.leq) were dissolved in a 1 : 1 mixture of methanol and DMF (32mL) and aqueous saturated sodium bicarbonate (3.2mL) was added. The reaction was run in 2 batches in 20mL vials in a microwave synthesis unit at 1300C for 15 minutes each. The resulting crude was concentrated and purified via silica gel chromatography to yield 3-Cyclohexyl-lH,leta-[2,7']biindolyl-6- carboxylic acid methyl ester (1.1Og, 99% yield). MS: 373.1 (M+H+); H.-NMR (DMSO d6): 11.58 (s, IH), 10.92 (s, IH), 7.99 (s, IH), 7.84 (d, IH, J=8.4Hz), 7.62 (m, 2H), 7.29 (m, IH), 7.13 (m, 2H), 6.53 (m, IH), 3.85 (s, IH), 2.71 (m, IH), 1.79 (m, 7H), 1.25 (m, 3H).

Reference： [1]Patent: WO2009/86139,2009,A1 .Location in patent: Page/Page column 115

10
[ 1169856-73-8 ]
[ 642494-37-9 ]
[ 1169856-74-9 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 130℃; for 0.25h;Microwave;	The whole amount of 2-bromo-3-cyclohexyl-l-(2-methoxymethoxy-ethyl)-lH- indole-6-carboxylic acid methyl ester from the previous step (2.974mmole) was combined with 794mg (3.27mmole) 7-(4,4,5,5-Tetramethyl-[l,3,2]dioxaborolan-2-yl)-lH-indole, 172mg (0.149mmole) tetrakis(triphenylphosphine)palladium(0), 12mL DMF and 3mL saturated aqueous NaHCO3 solution. The mixture was heated in a microwave reactor at 130 C for 15 minutes then it was evaporated to dryness and the residue was purified on a silica gel pad using toluene-ethyl acetate gradient. Yield: 1.034g (75.5% for two steps). MS (M+H+): 461.2; H.-NMR (DMSO d6): £(ppm) 10.84(s,lH), 8.15(d,lH, J=1.5Hz), 7.85 (d, IH, J=8.7Hz), 7.67 (m, 2H), 7.25 (m, IH), 7.14 (m, IH), 7.05(dd, IH, J=7.2Hz and 1.2Hz), 6.51 (m,lH), 4.20 (m, 3H), 3.87 (m, 4H), 3.41 (m, 2H), 2.89 (s, 3H), 2.45 (m, IH), 1.9-1.1 (m, 10H).

Reference： [1]Patent: WO2009/86139,2009,A1 .Location in patent: Page/Page column 116-117

11
(+/-)-6-bromo-5,7-difluoro-1,2,3,4-tetrahydro-3β-hydroxy-2,2,4α-trimethylquinoline [ No CAS ]
[ 642494-37-9 ]
(+/-)-5,7-difluoro-1,2,3,4-tetrahydro-3β-hydroxy-6-(indol-7-yl)-2,2,4α-trimethylquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; at 95 - 100℃; for 16 - 24h;	(+/-)-5,7-Difluoro-l,2,3,4-tetrahydro-3beta-hydroxy-6-(indol-7-yl)-2,2,4alpha- trimethylquinoline was prepared from (+/-)-6-bromo-5,7-difluoro-l,2,3,4-tetrahydro-3beta- hydroxy-2,2,4alpha-tetramethylquinoline and 7-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2- yl)indole using General Method 4. General Method 4: Palladium-catalyzed Suzuki cross-coupling of an aryl halide and an aryl boronic acid or aryl pinacol boronate. In a Schlenck reaction flask, a mixture of an aryl bromide (1 equiv); an aryl boronic acid or aryl pinacol boronate (1.0-1.3 equiv); and [l,r-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (3-10 mol %) is placed under vacuum, and back-filled with nitrogen. Dioxane (0.1-0.2 M) and 2M sodium carbonate (2 equiv) are introduced sequentially. The mixture is heated (95-100 0C) for 16-24 h. The mixture is partitioned between saturated ammonium chloride and EtOAc, resulting in a first organic layer and an aqueous layer. The first organic layer is collected and the aqueous layer is extracted with EtOAc. The organic layer from that extraction is combined with the first collected organic layer and that combined organic layer is washed with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. Flash chromatography (silica gel, EtOAc/hexanes or other specified solvent), preparative thin-layer chromatography (prep TLC, EtOAc/hexanes or other specified solvents), preparative HPLC and/or recrystallization affords the desired compound.

Reference： [1]Patent: WO2009/103007,2009,A2 .Location in patent: Page/Page column 83

12
1-diethylsilylindole [ No CAS ]
[ 73183-34-3 ]
[ 25015-63-8 ]
[ 642494-37-9 ]

Reference： [1]Journal of the American Chemical Society,2010,vol. 132,p. 4068 - 4069

13
C₁₈H₂₈BNO₂Si [ No CAS ]
[ 642494-37-9 ]

Reference： [1]Journal of the American Chemical Society,2010,vol. 132,p. 4068 - 4069

14
C₁₆H₂₄BNO₂Si [ No CAS ]
[ 642494-37-9 ]

Reference： [1]Journal of the American Chemical Society,2010,vol. 132,p. 4068 - 4069

15
[ 108-86-1 ]
[ 642494-37-9 ]
[ 1863-21-4 ]

Reference： [1]Journal of the American Chemical Society,2010,vol. 132,p. 4068 - 4069

16
[ 103-54-8 ]
[ 642494-37-9 ]
[ 1219637-86-1 ]

Reference： [1]Journal of the American Chemical Society,2010,vol. 132,p. 4068 - 4069

17
[ 642494-37-9 ]
[ 53924-05-3 ]

Reference： [1]Journal of the American Chemical Society,2010,vol. 132,p. 4068 - 4069
[2]Angewandte Chemie - International Edition,2019,vol. 58,p. 15381 - 15385
Angew. Chem.,2019,vol. 131,p. 15525 - 15529,5

18
[ 642494-37-9 ]
[ 51417-51-7 ]

Reference： [1]Journal of the American Chemical Society,2010,vol. 132,p. 4068 - 4069

19
[ 51417-51-7 ]
[ 642494-37-9 ]

Yield	Reaction Conditions	Operation in experiment
		<Step 1> Synthesis of 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole was obtained by performing the same procedure as in <Step 1> of Preparation Example 1, except that 7-bromo-1H-indole (25 g, 0.128 mol) was used instead of the 5-bromo-1H-indole used in <Step 1> of Preparation Example 1.

Reference： [1]Heterocycles,2010,vol. 80,p. 1267 - 1274
[2]Patent: US2015/318483,2015,A1

20
[ 51417-51-7 ]
[ 642494-37-9 ]
[ 66134-22-3 ]

Reference： [1]Heterocycles,2010,vol. 80,p. 1267 - 1274

21
[ 1426095-85-3 ]
[ 642494-37-9 ]
[ 1426095-20-6 ]

Yield	Reaction Conditions	Operation in experiment
105 mg	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 80℃;Inert atmosphere;	A -[(3 ?)-1 -Cyclopropylcarbonyl)-3^yrrolidinyl]methyl}-A -ethyl-4-(1 H-indol-7- yl)benzamideTo a solution of 4-bromo-/V-[(3R)-1-Cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-//- ethylbenzamide (200 mg) in 1 ,4-dioxane (4 mL) was added <strong>[642494-37-9]indole-7-boronic acid pinacol ester</strong> (128.6 mg) and K2C03 (219 mg in 2 ml. water) and the reaction mixture was stirred briefly at RT. Pd(dppf)CI2 (100 mg) was then added and the reaction vessel was flushed with nitrogen three times. The reaction mixture was heated at 80 C overnight. Solvent was then removed under reduced pressure and the residue partitioned between EtOAc and water. The EtOAc layer was separated, washed with saturated brine and evaporated to dryness. The crude product was purified by preparative reverse phase HPLC to afford 105 mg of the titled compound. LCMS m/z 416.1 (M+H).

Reference： [1]Patent: WO2013/28445,2013,A1 .Location in patent: Page/Page column 73; 74

22
[ 1426095-96-6 ]
[ 642494-37-9 ]
[ 1426095-33-1 ]

Yield	Reaction Conditions	Operation in experiment
59 mg	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 80℃;Inert atmosphere;	A -[(3 ?)-1 -Cyclopropylcarbonyl)-3^yrrolidinyl]methyl}-4-(1H-indol-7-yl)-A -(1 - methylethyl)benzamideTo a solution of 4-bromo-/V-[(3R)-1 -Cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-//-(1 - methylethyl)benzamide (150 mg) in 1 ,4-dioxane (2 mL) was added <strong>[642494-37-9]indole-7-boronic acid pinacol ester</strong> (1 10 mg), K2C03 (104 mg) and water (1 mL) and the reaction mixture was stirred briefly at RT. Pd(dppf)CI2 (27 mg) was then added under nitrogen. The reaction vessel was flushed with nitrogen three times and then stirred at 80 C overnight. The solvent was removed under reduced pressure and the residue partitioned between water and EtOAc. The organic layer was separated, washed with saturated brine and evaporated to dryness. The crude product was purified by preparative HPLC to afford 59 mg of the titled compound. LCMS m/z 430.3 (M+H).

Reference： [1]Patent: WO2013/28445,2013,A1 .Location in patent: Page/Page column 80

23
[ 1426095-72-8 ]
[ 642494-37-9 ]
[ 1426095-06-8 ]

Yield	Reaction Conditions	Operation in experiment
83 mg	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 80℃;Inert atmosphere;	W-[(3S)-1 -Cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-4-(1 H-indol-7-yl)-W- methylbenzamideTo a solution of 4-bromo-N-[(3S)-1 -Cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-N- methylbenzamide (150 mg) in 1 ,4-dioxane (4 mL) was added <strong>[642494-37-9]indole-7-boronic acid pinacol ester</strong> (90.2 mg) and K2C03 (171 .1 mg in 2 mL water) and the reaction mixture was stirred briefly at RT. Pd(dppf)CI2 (100 mg) was then added and the reaction vessel was flushed with nitrogen three times. The reaction mixture was heated at 80 C overnight. Solvent was then removed under reduced pressure and the residue partitioned between EtOAc and water. The EtOAc layer was separated, washed with saturated brine and evaporated to dryness. The crude product was purified by preparative reverse phase HPLC to afford 83 mg of the titled compound. LCMS m/z 402.2 (M+H).

Reference： [1]Patent: WO2013/28445,2013,A1 .Location in patent: Page/Page column 65; 66

24
[ 1426096-05-0 ]
[ 642494-37-9 ]
[ 1426095-45-5 ]

Yield	Reaction Conditions	Operation in experiment
120 mg	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 80℃;Inert atmosphere;	Lambda -[(3 ?)-1 -Cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-4-(1 H-indol-7-yl)-W- (phenylmethyl)benzamideTo a solution of 4-bromo-/V-[(3R)-1-Cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-//- (phenylmethyl)benzamide (150 mg) in 1 ,4-dioxane (4 mL) was added 7-indoleboronic acid pinacol ester (91 .15 mg) and K2C03 (141.1 mg in 2 mL water) and the reaction mixture stirred briefly at RT. Pd(dppf)CI2 (100 mg) was added under nitrogen and the reaction vessel was flushed with nitrogen 3 times. The reaction mixture was stirred at 80 C overnight.Solvent was removed under reduced pressure and the residue partitioned between water and EtOAc. The EtOAc layer was separated, washed with saturated brine, evaporated to dryness and purified by preparative HPLC to afford 120 mg of the titled compound. LCMS m/z 478.2 (M+H).

Reference： [1]Patent: WO2013/28445,2013,A1 .Location in patent: Page/Page column 85

25
[ 944058-89-3 ]
[ 642494-37-9 ]
[ 1426153-99-2 ]

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 2125 - 2138

26
[ 642494-37-9 ]
7-(2-nitropyridin-3-yl)-1H-indole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		<Step 2> Synthesis of 7-(2-nitropyridin-3-yl)-1H-indole 7-(2-nitropyridin-3-yl)-1H-indole was obtained by performing the same procedure as in <Step 2> of Preparation Example 1, except that the <strong>[642494-37-9]7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole</strong> obtained in <Step 1> and 3-bromo-2-nitropyridine were used instead of 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole and 2-chloro-3-nitropyridine. 1H-NMR: delta 6.45 (d, 1H), 7.26 (d, 1H), 7.44 (t, 1H), 7.55 (d, 1H), 7.72 (d, 1H), 8.22 (m, 2H), 8.41 (d, 1H), 8.52 (d, 1H)

Reference： [1]Patent: US2015/214490,2015,A1 .Location in patent: Page/Page column

27
[ 642494-37-9 ]
1-(2,2'-bipyridin-5-yl)-7-(2-nitropyridin-3-yl)-1H-indole [ No CAS ]

Reference： [1]Patent: US2015/214490,2015,A1

28
[ 642494-37-9 ]
7-(2-nitrophenyl)-1H-indole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		<Step 2> Synthesis of 7-(2-nitrophenyl)-1H-indole 7-(2-nitrophenyl)-1H-indole was obtained by performing the same procedure as in <Step 2> of Preparation Example 1, except that the <strong>[642494-37-9]7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole</strong> obtained in <Step 1> was used instead of 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole. 1H-NMR: delta 6.42 (d, 1H), 7.24 (d, 1H), 7.43 (t, 1H), 7.55 (d, 1H), 7.70 (m, 2H), 7.88 (t, 1H), 8.01 (d, 1H), 8.11 (d, 1H), 8.23 (s, 1H)

Reference： [1]Patent: US2015/236272,2015,A1

29
[ 642494-37-9 ]
7-(2-nitrophenyl)-1-phenyl-1H-indole [ No CAS ]

Reference： [1]Patent: US2015/236272,2015,A1

30
ethyl 1-(6-bromopyridin-2-yl)-5-ethyl-1H-pyrazole-4-carboxylate [ No CAS ]
[ 642494-37-9 ]
ethyl 1-(6-(1H-indol-7-yl)pyridin-2-yl)-5-ethyl-1H-pyrazole-4-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In water; acetonitrile; at 70℃; for 16h;Sealed tube;	Bis(triphenylphosphine)palladium(ll) dichloride (0.1 1 g, 0.154 mmol) was added to a solution of 7-(4,4,5,5-tetramethyl-1 , 3, 2-dioxaborolan-2-yl)-1 /-/-indole (0.84 g, 3.45 mmol) and Intermediate 1 -4-2 (1 g, 3.08 mmol) in acetonitrile (16 mL) and 1 .0 M Na2C03 (9.25 mL, 9.25 mmol). The reaction mixture was sealed and stirred at 70 C for 16 h. The mixture was then cooled to room temperature, and then filtered through a plug of Celite. The filtrate was diluted with EtOAc and the organic layer was washed successively with H20 and brine. The organic layer was dried over Na2S04, filtered, and then concentrated. The resulting residue was purified by flash column chromatography on silica gel (0-50% EtOAc/heptane gradient) to afford the title compound. MS (ESI+) /z 361 .3 (M+H).

Reference： [1]Patent: WO2016/1875,2016,A1 .Location in patent: Page/Page column 83-84

31
[ 642494-37-9 ]
ethyl 5-ethyl-1-(6-(indolin-7-yl)pyridin-2-yl)-1H-pyrazole-4-carboxylate [ No CAS ]