[ CAS No. 40432-84-6 ] {[proInfo.proName]}

Name: 40432-84-6|2-(5-Bromo-1H-indol-3-yl)acetic acid|95%
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SKU: A256315
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Quality Control of [ 40432-84-6 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 40432-84-6 ]

CAS No. :	40432-84-6	MDL No. :	MFCD00005637
Formula :	C₁₀H₈BrNO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	WTFGHMZUJMRWBK-UHFFFAOYSA-N
M.W :	254.08	Pubchem ID :	96734
Synonyms :

Calculated chemistry of [ 40432-84-6 ]

Physicochemical Properties

Num. heavy atoms :	14
Num. arom. heavy atoms :	9
Fraction Csp3 :	0.1
Num. rotatable bonds :	2
Num. H-bond acceptors :	2.0
Num. H-bond donors :	2.0
Molar Refractivity :	57.54
TPSA :	53.09 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.36 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.45
Log Po/w (XLOGP3) :	2.1
Log Po/w (WLOGP) :	2.56
Log Po/w (MLOGP) :	1.81
Log Po/w (SILICOS-IT) :	2.88
Consensus Log Po/w :	2.16

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	0.0
Bioavailability Score :	0.56

Water Solubility

Log S (ESOL) :	-3.08
Solubility :	0.21 mg/ml ; 0.000828 mol/l
Class :	Soluble
Log S (Ali) :	-2.85
Solubility :	0.363 mg/ml ; 0.00143 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.92
Solubility :	0.0307 mg/ml ; 0.000121 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	0.0
Synthetic accessibility :	1.63

Safety of [ 40432-84-6 ]

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 [ 40432-84-6 ]

* 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 [ 40432-84-6 ]
Downstream synthetic route of [ 40432-84-6 ]

[ 40432-84-6 ] Synthesis Path-Upstream 1~7

1
[ 774-14-1 ]
[ 40432-84-6 ]

Reference： [1] Organic and Biomolecular Chemistry, 2012, vol. 10, # 10, p. 2101 - 2112

2
[ 10075-50-0 ]
[ 40432-84-6 ]

Reference： [1] Tetrahedron Letters, 1994, vol. 35, # 19, p. 3013 - 3016
[2] Organic and Biomolecular Chemistry, 2012, vol. 10, # 10, p. 2101 - 2112
[3] Journal of the American Chemical Society, 2012, vol. 134, # 26, p. 10815 - 10818

3
[ 156695-44-2 ]
[ 40432-84-6 ]

Reference： [1] Tetrahedron Letters, 1994, vol. 35, # 19, p. 3013 - 3016
[2] Journal of the American Chemical Society, 2012, vol. 134, # 26, p. 10815 - 10818

4
[ 830-93-3 ]
[ 40432-84-6 ]

Reference： [1] Organic and Biomolecular Chemistry, 2012, vol. 10, # 10, p. 2101 - 2112

5
[ 63843-81-2 ]
[ 40432-84-6 ]

Reference： [1] Tetrahedron Letters, 1994, vol. 35, # 19, p. 3013 - 3016

6
[ 40432-84-6 ]
[ 32774-29-1 ]

Reference： [1] Journal of Medicinal Chemistry, 2007, vol. 50, # 8, p. 1810 - 1827
[2] Patent: WO2011/14128, 2011, A1,

7
[ 40432-84-6 ]
[ 142273-20-9 ]

Reference： [1] Organic and Biomolecular Chemistry, 2012, vol. 10, # 10, p. 2101 - 2112

[ 40432-84-6 ] Synthesis Path-Downstream 1~88

1
[ 40432-84-6 ]
[ 87-51-4 ]

Reference： [1]Phytochemistry,1982,vol. 21,p. 2879 - 2886

2
[ 40432-84-6 ]
[ 82462-44-0 ]

Reference： [1]Phytochemistry,1982,vol. 21,p. 2879 - 2886

3
[ 40432-84-6 ]
[ 40432-84-6 ]

Reference： [1]Journal of Physical Chemistry,1992,vol. 96,p. 6674 - 6679

4
[ 40432-84-6 ]
[ 98930-01-9 ]
bis-Fmoc protected spermidine attached to an aminomethyl polystyrene resin via an acid cleavable Wang type urethane linker [ No CAS ]
C₅₉H₇₉Br₂N₁₃O₁₀S₂ [ No CAS ]

Reference： [1]Tetrahedron Letters,2003,vol. 44,p. 3195 - 3197

5
[ 40432-84-6 ]
[ 139090-50-9 ]
bis-Fmoc protected spermidine attached to an aminomethyl polystyrene resin via an acid cleavable Wang type urethane linker [ No CAS ]
C₅₃H₆₇Br₂N₁₃O₈S₂ [ No CAS ]

Reference： [1]Tetrahedron Letters,2003,vol. 44,p. 3195 - 3197

6
[ 681211-35-8 ]
[ 40432-84-6 ]
2-(5-bromo-1H-indol-3-yl)-N-[7-(6-chloro-1,2,3,4-tetrahydro-acridin-9-ylamino)-heptyl]-acetamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 7223 - 7233

7
4-(7-nitrobenzo[1,2,5]oxadiazo-4-yl)piperazine hydrochloride [ No CAS ]
[ 40432-84-6 ]
2-(5-bromo-1H-indol-3-yl)-1-[4-(7-nitro-benzo[1,2,5]oxadiazol-4-yl)-piperazin-1-yl]-ethanone [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 3378 - 3390

8
[ 186581-53-3 ]
[ 40432-84-6 ]
1-(5-bromo-1H-indol-3-yl)-3-diazo-propan-2-one [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 10 - 20

9
[ 69097-20-7 ]
[ 40432-84-6 ]
1-(5-bromo-1H-indol-3-yl)-3-hydroxy-propan-2-one [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 10 - 20

10
[ 40432-84-6 ]
[ 501-53-1 ]
[ 919295-63-9 ]

Yield	Reaction Conditions	Operation in experiment
92%		Example 3 Synthesis of compound 2: 5-bromo-3-hydroxycarbamoylmethyl-indole-1-carboxylic acid benzyl ester [Show Image] The carboxymethylation procedure described in Horwell et al. (1997) was followed from 2-(5-bromo-indol-3-yl)acetic acid (200mg, M =254,09, 0.787 mmoL) to give 3-carboxymethyl-5-bromo-indol-1-carboxylic acid benzyl ester (280 mg, yield: 92%). Rf (silica gel CH2Cl2/CH3OH 9/1 v:v mixture) = 0.5, Tf = 88C, IR (cm-1): 1729 and 1692 (nuVO). 1H NMR (250 MHz, [d6] acetone): delta 3.80 (s, 2H); 5.51 (s, 2H); 7.24-7.82 (m, 8H); 8.12 (d, J = 8.1, 1H); 11,16 (s, 1H). CI-MS: m/z = 388 [M]. el. anal.: (C18H14BrNO4).0.5 H2O C,H,N. Starting from 3-carboxymethyl-5-bromo-indol-1-carboxylic acid benzyl ester (120 mg, M = 388.21, 0.309 mmoL), 50 mg of 2 was obtained in a 40 % yield, according to the previously described method. 1H NMR (250 MHz, [d6] DMSO): delta 3.43 (s, 2H); 5.52 (s, 2H); 7.50-7.60 (m, 7H); 7.91 (s, 1H); 8.07(d, J = 8.5, 1H); 8.97 (s, 1H); 10.72 (s, 1H). CI-MS: m/z = 404 [M + H+]. Anal.: (C18H15BrN2O4) C,H,N.; N-substituted indole can be prepared as described in Scheme 4. [Show Image] W represents a halogen, an alkyl, an aryl, an alkoxy, an aryloxy or a thioaryl group. Briefly, N-carboxymethylation is achieved by reaction of the lithio derivative (prepared with two equiv. of lithium bis(trimethylsilyl)amide in THF at -78C) with benzylchloroformate (Horwell et al., 1997).

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 10 - 20
[2]Patent: EP1683521,2006,A1 .Location in patent: Page/Page column 10; 14
[3]Journal of Medicinal Chemistry,2007,vol. 50,p. 40 - 64

11
[ 40432-84-6 ]
2-(5-bromo-1H-indol-3-yl)-N-hydroxyacetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%		Briefly, to a 10 ml DMF solution of the indolacetic acid derivative (0.3 mmol) are added 1-hydroxybenzotriazole (1.1 equiv., m = 44 mg), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.1 equiv., m = 63 mg) and N-methylmorpholine (1.1 equiv., 36 muL). This solution is stirred for one hour at r.t. After adding hydroxylamine hydrochloride (1.1 equiv., m = 23 mg) the solution is left under stirring overnight. Then DMF is evaporated under vacuo, and ethylacetate is added to the residue. This ethylacetate solution is successively washed with water, saturated aqueous NaHCO3 solution and saturated aqueous NaCl solution. After drying over Na2SO4 and filtration, evaporation of the solvent to dryness affords hydroxamic acid derivatives in 40-60 % yield. A substitution at position 2 of the indolic derivatives can proceed as described in Scheme 3. W represents a halogen, an alkyl, an aryl, an alkoxy, an aryloxy, or a thioaryl group. Briefly, reaction 2-lithio-N-benzensulfonylindole (obtained by reaction of N-benzensulfonylindole with BuLi) with dimethyloxalate (Hasan et al., 1981) successively followed by basic hydrolysis and Wolf-kishner reduction affords the (indol-2-yl)acetic acid (Weller & Ford, 1984).; Example 2 Synthesis of compound 1: 2-(5-Bromo-1H-indol-3-yl)-N-hydroxyacetamide [Show Image] Materials and methods All solvents and chemicals were purchased from SDS and Aldrich, respectively. DMF, THF and CH2Cl2 were dried using standard procedures and stored over 4 A molecular sieves under an argon atmosphere. 1H NMR spectra were recorded on a Bruker ARX-250 spectrometer and chemical shifts were reported in ppm downfield from TMS. IR spectra were obtained with a Perkin-Elmer Spectrum One FT-IR spectrometer equipped with a MIRacle single reflection horizontal ATR unit (Zirconium-Selenium crystal). FAB and CI Mass spectra were recorded at ENS in Paris. Elemental analyses were carried out by the microanalysis service at Paris VI University (France) or at Gif-sur-Yvette (CNRS, France). Experiments performed under argon were run on a vacuum line.Results Starting from commercial <strong>[40432-84-6]2-(5-bromo-1H-indol-3-yl)acetic acid</strong> (200 mg; M = 254.09, 0.787 mmoL), 116 mg of 1 was obtained in a 55% yield, according to the previously described method. Rf(C18 silica gel, ethylacetate/methanol 1/1 v:v mixture) = 0.8. Tf = 145C. IR (cm-1): 3417 (nuOH) 3213 (nuNH), 1633 (nuCO). 1H NMR (250 MHz, [d6] DMSO): delta 3.49 (s, 2H); 7.20-7.5 (m, 3H); 7.87 (s, 1H); 8.86 (s, 1H) ; 10.59 (s, 1H) ; 11.14 (s, 1H). CI-MS : m/z = 270 (M + H+). Anal.: (C10H9BrN2O2) C,H,N.

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 10 - 20
[2]Patent: EP1683521,2006,A1 .Location in patent: Page/Page column 10; 13-14
[3]Organic Letters,2016,vol. 18,p. 2228 - 2231

12
[ 40432-84-6 ]
[ 32774-29-1 ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 1810 - 1827
[2]Patent: WO2011/14128,2011,A1

13
[ 67-56-1 ]
[ 40432-84-6 ]
[ 117235-22-0 ]

Yield	Reaction Conditions	Operation in experiment
89%		Methyl-2-(5-bromo-li/-indol-3-yl)acetate (12). To a solution of 2 (5- bromo-lH-indol-3-yl)acetic acid (4 mmol) in 20 mL of MeOH was added 10 drops of concentrated sulphuric acid. The mixture was heated under reflux with continuous stirring for a period of 1-1.5 h. Following reflux, the reaction mixture was cooled to room temperature and evaporated in vacuo. The residue was added with a saturated solution of NaHCO3 (50 mL) to neutralize acid, and the resulting alkaline aqueous mixture was extracted with EtOAc and dried over Na2SO4. Evaporation of the solvent gave a residue which was purified by flash silica gel column chromatography. Elution with CH2Cl2 yielded the corresponding ester 11 as an off- white solid. Yield: 89 %; 1H NMR (300 MHz, CDCl3): delta 3.66 (s, 3 H), 3.68 (s, 2 H), 7.18-7.21 (m, 4 H); MS (APCI), mlz 269.2 [M + H]+.
88%	With toluene-4-sulfonic acid; at 75℃; for 16h;Inert atmosphere;	A solution of 2-(5-bromo-1H-indol-3-yl) acetic acid (500 mg, 1.97 mmol) anhydrous MeOH (100 mL) was treated with PTSA (34 mg, 0.197 mmol) and heated at 75C for 16 h. The mixture was concentrated, the residue was dissolved in CH2C12 (50 mL), washed with water (3 X 20 mL) and brine (20 mL). The CH2C12 layer was separated, dried (Na2SO4), filtered and concentrated to give methyl 2-(5-bromo-1H-indol-3-yl) acetate as a dark red solid (465 mg, 88%). ESI-MS m/z 268[M]t
	With chloro-trimethyl-silane; at -20℃;	Chlorotrimethylsilane (6 mL) was added to methanol (50 mL) and cooled to -200C, then combined immediately with another solution comprising methanol (50 mL) and 5 -Bromoindole-3 -acetic acid (1.04 g). The reaction mixture was stirred overnight under argon. The solvents were evaporated under vacuum and the crude product dried overnight providing methyl 2-(5-Bromo-lH-indol-3-yl)acetate. The crude methyl ester was used in the next step without any further purification.

Reference： [1]Organic and Biomolecular Chemistry,2012,vol. 10,p. 2101 - 2112
[2]Journal of Agricultural and Food Chemistry,2016,vol. 64,p. 3533 - 3537
[3]Journal of Medicinal Chemistry,2010,vol. 53,p. 6838 - 6850
[4]Patent: WO2011/14128,2011,A1 .Location in patent: Page/Page column 64-65
[5]Patent: WO2019/88910,2019,A1 .Location in patent: Page/Page column 18; 68; 69
[6]Journal of Medicinal Chemistry,2007,vol. 50,p. 1810 - 1827
[7]Patent: WO2007/75931,2007,A2 .Location in patent: Page/Page column 25

14
[ 40432-84-6 ]
MRS 3854 [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 1810 - 1827

15
[ 40432-84-6 ]
[ 936252-32-3 ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 1810 - 1827

16
[ 40432-84-6 ]
[ 1027571-59-0 ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 1810 - 1827

17
[ 40432-84-6 ]
[ 936252-56-1 ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 1810 - 1827

18
[ 40432-84-6 ]
[ 936252-77-6 ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 1810 - 1827

19
[ 40432-84-6 ]
5-bromo-3-chlorocarbonylmethyl-indole-1-carboxylic acid benzyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 40 - 64

20
[ 40432-84-6 ]
[ 924635-01-8 ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 40 - 64

21
[ 40432-84-6 ]
benzyl 3-(3-acetoxy-2-oxopropyl)-5-bromo-1H-indole-1-carboxylate [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 40 - 64

22
[ 40432-84-6 ]
2-(5-bromo-1H-indol-3-ylmethyl)-3-hydroxy-7,8,9,10-tetrahydro-benzo[h]quinoline-4-carboxylic acid [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 40 - 64

23
[ 40432-84-6 ]
thioacetic acid S-[3-(5-bromo-1H-indol-3-yl)-2-oxo-propyl] ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 10 - 20

24
[ 40432-84-6 ]
5-bromo-3-hydroxycarbamoylmethyl-indole-1-carboxylic acid benzyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 10 - 20

25
[ 10075-50-0 ]
[ 40432-84-6 ]

Reference： [1]Tetrahedron Letters,1994,vol. 35,p. 3013 - 3016
[2]Organic and Biomolecular Chemistry,2012,vol. 10,p. 2101 - 2112
[3]Journal of the American Chemical Society,2012,vol. 134,p. 10815 - 10818
[4]Organic Letters,2020,vol. 22,p. 5656 - 5660

26
[ 63843-81-2 ]
[ 40432-84-6 ]

Reference： [1]Tetrahedron Letters,1994,vol. 35,p. 3013 - 3016

27
[ 156695-44-2 ]
[ 40432-84-6 ]

Reference： [1]Tetrahedron Letters,1994,vol. 35,p. 3013 - 3016
[2]Journal of the American Chemical Society,2012,vol. 134,p. 10815 - 10818

28
[ 86945-25-7 ]
[ 40432-84-6 ]
N-[2-(1-benzyl-piperidin-4-yl)-ethyl]-2-(5-bromo-1H-indol-3-yl)-acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%		General procedure: Under nitrogen protection was added to a solution of indole carboxilic/ethanolic acid derivates in THF, the 1,1' carbonyldiimidazol,and stirred for 4 h at room temperature. Then theamine was added and the resulting solution was stirred for 20 h, after this time the solvent was evaporated under reduced pressure and the residue purified by silica gel flash column chromatography using different gradients of solvents AcOEt/MeOH for each case.
15%	With 1,1'-carbonyldiimidazole; In tetrahydrofuran; at 20℃;	(4) N-[2-(1-Benzyl-piperidin-4-yl)-ethyl]-2-(5-bromo-1H-indol-3-yl)-acetamide Reagents: 5-bromoindole-3-acetic acid (221mg, 0.87mmol), THF 3ml, 1,1'carbonyldiimidazol (149.2 mg, 0.92 mmol), and 2-(1-Benzyl-piperidin-4-yl)-ethylamine (200mg, 0.92mmol). Conditions: Room temperature, overnight. Purification: silica gel column chromatography using AcOEt/ MeOH (5:0.1). Yield:60mg (15%).1H-NMR (CDCl3, 400MHz, delta ppm): (9.3, bs, 1H), (7.65, s, 1H), (7.29-7.20, m, 7H), (7.10, s, 1H), (5.71, m, 1H, NHCO), (3.65, s, 2H), (3.46, s, 2H), (3.25-3.17, m, 2H), (2.85-2.76, m, 2H), (1.88-1.80, m,2H), (1.56-1.48, m, 2H), (1.32-1.48, m,2H), (1.10-1.01, m, 3H). 13C-NMR (CDCl3): 170.6, 137.8, 134.7, 129.0, 128.4, 127.8, 126.6, 125.1, 124.6, 121.0, 112.9, 112.6, 108.3, 63.1, 53.2, 37.0, 35.6, 33.0, 32.9, 32.6. ESI-MS[M+H+]+453.14.

Reference： [1]European Journal of Medicinal Chemistry,2018,vol. 145,p. 431 - 444
[2]Patent: EP1600447,2005,A1 .Location in patent: Page/Page column 9

29
IPr₂NEt [ No CAS ]
[ 40432-84-6 ]
[ 7051-34-5 ]
[ 241497-50-7 ]

Yield	Reaction Conditions	Operation in experiment
86%	In 1-methyl-pyrrolidin-2-one; hexane; ethyl acetate;	EXAMPLE 77 2-[5-bromo-1-(cyclopropylmethyl)-1H-indol-3-yl]acetic acid To 5-bromoindole-3-acetic acid (890 mg, 3.5 mmol) in 1-methyl-2-pyrrolidinone (12 mL) at 0 C. were added iPr2NEt (21 mmol) and bromomethylcyclopropane (10.5 mmol). The reaction mixture was heated at 50 C. for 19 h before partitioning between diethyl ether and ice water. After adjusting the pH to 3, the aqueous layer was extracted with diethyl ether. The organic layers were combined, washed with NaH2PO4, dried over MgSO4 and evaporated to dryness. Purification on silica gel column (30% EtOAc in hexane) yielded 927 mg (86% yield) of the product.

Reference： [1]Patent: US6500853,2002,B1

30
[ 40432-84-6 ]
[ 74-88-4 ]
5-bromo-1-methyl-1H-indol-3-yl acetic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; In tetrahydrofuran; water; mineral oil;	a) 500 mg of a 60% dispersion of sodium hydride in mineral oil were added to solution of 1 g of 5-bromoindole-3-acetic acid in 50 ml of tetrahydrofuran and the mixture was stirred under a nitrogen atmosphere for 1 hour. Thereafter, 820 mg (5.8 mmol) of methyl iodide were added and the mixture was stirred under a nitrogen atmosphere for 24 hours. Then, 5 ml of water were added and the solvent was removed under reduced pressure. The residue was treated with 2M hydrochloric acid and the precipitate formed was filtered off, washed with n-hexane and dried. The obtained solid was recrystallized from diethyl ether to give 5-bromo-1-methyl-3-indolylacetic acid of melting point 192-194 C.

Reference： [1]Patent: US5721245,1998,A

31
[ 40432-84-6 ]
[ 885068-06-4 ]

Yield	Reaction Conditions	Operation in experiment
20%		Step 2To a solution of (5-bromo-lH-indol-3-yl)-acetic acid (I g, 3.94 mmol) in THF (66 mL) at -78 0C is added tert-butyl lithium (1.7 M in pentane, 11.6 mL, 19.7 mmol) dropwise and stirred at -780C for 30 minutes, at -3O0C for 1 hour. Cooled down to -780C again and treated dropwise with triisopropyl borate (4.53 mL, 19.7 mmol). The reaction mixture is allowed to warm to room temperature during 1 hour quenched with 2N hydrochloric acid. This mixture is extracted with ether. The extract is dried over sodium sulfate and concentrate to obtain an oil which is subjected to silica gel chromatography affording 3-carboxymethyl-lH-indol-5-yl boronic acid (185 mg, 20%) as a solid.
20%		To a solution of (5-bromo-lH-indol-3-yl)-acetic acid (1 g, 3.94 mmol) in THF (66 mL) at -78 0C is added tert-butyl lithium (1.7 M in pentane, 11.6 mL, 19.7 mmol) dropwise and stirred at -780C for 30 minutes, at -3O0C for 1 hour. Cooled down to -780C again and treated dropwise with triisopropyl borate (4.53 mL, 19.7 mmol). The reaction mixture is allowed to warm to room temperature during 1 hour quenched with 2N hydrochloric acid. This mixture is extracted with ether. The extract is dried over sodium sulfate and concentrate to obtain an oil which is subjected to silica gel chromatography affording 3-carboxymethyl-lH-indol-5-yl boronic acid (185 mg, 20%) as a solid.

Reference： [1]Patent: WO2006/44732,2006,A2 .Location in patent: Page/Page column 176
[2]Patent: WO2008/39882,2008,A1 .Location in patent: Page/Page column 175

32
[ 40432-84-6 ]
[ 18107-18-1 ]
[ 117235-22-0 ]

Yield	Reaction Conditions	Operation in experiment
99%	In methanol; hexane; at 20℃; for 0.0333333h;	Preparation 9 (5-Bromo-lH-indol-3-yl)-acetic acid methyl esterTo a solution of (5-bromo-lH-indol-3-yl)-acctic acid (683 mg, 2.69 mmol) in methanol (6 mL) is added (trimethylsilyl)diazomethane (2.0 M solution in hexanes, approximately 6 mL) over two minutes at room temperature. The yellow mixture is concentrated. The residue is taken up in methanol and is concentrated several times to give of the title compound (710 mg, 99%). ES/MS m/e 266.2 (M-2).
85%	In methanol; diethyl ether; hexane; at 20℃; for 2h;	Preparation H; 2-(5-cyano-1H-indol-3-yl)acetic acid; Step H (1); To a solution of <strong>[40432-84-6]2-(5-bromo-1H-indol-3-yl)acetic acid</strong> (1.0 g 3.94 mmol) in MeOH (5 mL) and Et2O (15 mL) was added (trimethylsilyl)diazomethane (2.0 M solution in hexanes, 10 mL). The reaction was stirred at rt for 2 h. The solvents were removed and the residue was purified by flash chromatography to yield 900 mg of methyl 2-(5-bromo-1H-indol-3-yl)acetate (yield 85%). 1H NMR (500 MHz, CDCl3) delta ppm 3.71 (s, 3H) 3.72 (s, 2H) 7.16 (d, J=2.14 Hz, 1H) 7.21 (d, J=8.55 Hz, 1H) 7.27 (dd, J=8.55, 1.83 Hz, 1H) 7.72 (d, J=1.53 Hz, 1H) 8.12 (s, 1H)

Reference： [1]Patent: WO2007/92751,2007,A2 .Location in patent: Page/Page column 14
[2]Patent: US2007/49589,2007,A1 .Location in patent: Page/Page column 14

33
[ 40432-84-6 ]
[ 196081-79-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 2395 - 2398
[2]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 2390 - 2394

34
C₁₆H₂₄N₂ [ No CAS ]
[ 40432-84-6 ]
C₂₆H₃₀BrN₃O [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 2860 - 2864

35
[ 31252-42-3 ]
[ 40432-84-6 ]
[ 1134099-84-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2009,vol. 17,p. 1640 - 1647

36
[ 111-83-1 ]
[ 40432-84-6 ]
[ 1244769-52-5 ]

Yield	Reaction Conditions	Operation in experiment
70%		Example 2: Synthesis of Compounds of Series 2, Table 2 Scheme 2: Preparation of 3 amides (Jl, J2, J4-6, J7, JIl)m-tolyl boric acid/EtOH DME, Pd(PPh3)4, K2CO3, 58 %10 (J1, J2, J4-6, J7, J11) JlO, J16, J21 and J22 were prepared following the experimental procedure Example 1, Scheme 1 [0096J 2-(5-bromo-l-octyl-lH-indoI-3-yl)acetic acid (7): To a stirred suspension of NaH (5.54 g, 138 mmol, 60% dispersion in mineral oil) in THF (100 mL THF ) at 0 0C was added a solution of indole-3-acetic acid (6.65 g, 27.7 mmol) in THF (50 mL). After stirring the mixture for 30 min at 0 0C, a solution of 1-Bromo Octane (14.3 mL, 83.1 mmol) in THF (50 mL) was added drop wise. The mixture was allowed to slowly reach room temp and continued to stir for 4 h. The reaction mixture was then cooled to 0 0C and excess hydride was carefully destroyed by slow addition of MeOH with vigorous stirring followed by cold water until a clear yellow solution resulted. Ether (100 mL) was added. The aqueous phase was separated, acidified with 6 N HCl, and extracted with sufficient dichloromethane 3 times. The combined dichloromethane extracts were dried (Na2SO4) and concentrated, purified by crystallisation in chloroform subsequently column chromatography using ethylacetate.

Reference： [1]Patent: WO2011/14128,2011,A1 .Location in patent: Page/Page column 35
[2]Journal of Medicinal Chemistry,2010,vol. 53,p. 6838 - 6850

37
[ 40432-84-6 ]
[ 1244769-70-7 ]

Reference： [1]Patent: WO2011/14128,2011,A1

38
[ 40432-84-6 ]
[ 1244769-23-0 ]

Reference： [1]Patent: WO2011/14128,2011,A1

39
[ 40432-84-6 ]
[ 1310452-37-9 ]

Reference： [1]Patent: WO2011/14128,2011,A1

40
[ 40432-84-6 ]
[ 1244769-67-2 ]

Reference： [1]Patent: WO2011/14128,2011,A1

41
[ 40432-84-6 ]
[ 1244769-20-7 ]

Reference： [1]Patent: WO2011/14128,2011,A1

42
[ 40432-84-6 ]
[ 1244769-59-2 ]

Reference： [1]Patent: WO2011/14128,2011,A1

43
[ 75-77-4 ]
[ 40432-84-6 ]
[ 117235-22-0 ]