474706-74-6|6-Bromo-3-iodoimidazo[1,2-a]pyridine| Ambeed

Structure of 474706-74-6

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Quality Control of [ 474706-74-6 ] Purity: 96% SDS Specification

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Product Details of [ 474706-74-6 ]

CAS No. :	474706-74-6
Formula :	C₇H₄BrIN₂
M.W :	322.93
SMILES Code :	IC1=CN=C2C=CC(Br)=CN21
MDL No. :	MFCD18800553
InChI Key :	VADGFPDSVWQCHR-UHFFFAOYSA-N
Pubchem ID :	22031632

Safety of [ 474706-74-6 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Computational Chemistry of [ 474706-74-6 ] Show Less

Physicochemical Properties

Num. heavy atoms	11
Num. arom. heavy atoms	9
Fraction Csp3	0.0
Num. rotatable bonds	0
Num. H-bond acceptors	1.0
Num. H-bond donors	0.0
Molar Refractivity	55.61
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	17.3 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.37
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	3.14
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.7
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	2.35
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	2.59
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.63

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-4.43
Solubility	0.0121 mg/ml ; 0.0000375 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Moderately soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-3.17
Solubility	0.217 mg/ml ; 0.000672 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-3.87
Solubility	0.0441 mg/ml ; 0.000136 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	Yes
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	Yes
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-6.04 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	0.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	1.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<0.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	2.28

Application In Synthesis of [ 474706-74-6 ]

* 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.

Downstream synthetic route of [ 474706-74-6 ]

[ 474706-74-6 ] Synthesis Path-Downstream 1~35

1
[ 474706-74-6 ]
[ 1692-15-5 ]
6-bromo-3-pyridin-4-ylimidazo[1,2-a]pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
38%	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 100℃; for 16h;	6-Bromo-3-iodoimidazo[l,2-alpha]pyridine (6.57 g, 20.3 mmol), pyridine 4- boronic acid (2.50 g, 20.3 mmol), Pd(PPh3)4 (1.17 g, 1.01 mmol) aq. K2CO3 (8.42 g, 61.0 mmol in 50 mL of water) and 1,4-dioxane (150 mL) were combined in a sealed tube and heated to 100 0C. After 16 h, the reaction was cooled to rt and concentrated under reduced pressure. The solid residue was triturated with water, collected by filtration and azeotroped with CH2Cl2. The crude product dissolved in boiling CHCl3, and insoluble impurities were removed by filtration. Concentration of the filtrate followed by silica gel chromatography (0 to 3 to 5% MeOH/CHCl3) provided 2.12 g (38%) of the title compound as a yellow solid. MS(ES)+ m/e 275.9 [M+H]+.

References: [1]Patent: WO2008/14219,2008,A2 .Location in patent: Page/Page column 45.

2
[ 474706-74-6 ]
[ 97674-02-7 ]
[ 30493-41-5 ]

Yield	Reaction Conditions	Operation in experiment
64%		A mixture of 6-bromo-3-iodoimidazo[l,2-alpha]pyridine (3.0 g, 9.29 mmol), 1- ethoxyvinyltri-n-butyltin (3.3 mL, 9.75 mmol) and dichlorobis(triphenylphosphine)- palladium(II) (325 mg, 0.46 mmol) in 1,4-dioxane (90 mL) was heated to 100 0C in a sealed tube for 16 h. The reaction mixture was cooled to rt, diluted with ethyl acetate, filtered through a pad of silica gel (elute with ethyl acetate) and concentrated under reduced pressure. The residue was taken up in THF (50 mL) and treated with 6N HCl (3.1 mL, 18.6 mmol). After 1 h, the mixture was concentrated under reduced pressure, triturated with water and adjusted to pH ~12 with IN NaOH. The mixture was extracted 3 X with ethyl acetate and the combined extracts were dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography (97:3 EtOAc/MeOH) to give 1.41 g (64%) of l-(6-bromoimidazo[l,2-alpha]pyridin-3-yl)ethanone as a pale yellow solid. MS(ES)+ m/e 240.7 [M+H]+.

References: [1]Patent: WO2008/14219,2008,A2 .Location in patent: Page/Page column 47.

3
[ 474706-74-6 ]
[ 121359-48-6 ]
[ 474706-87-1 ]

Yield	Reaction Conditions	Operation in experiment
	tetrakis(triphenylphosphine) palladium(0); In xylene; at 110℃; for 10h;	Production Example 57 2-(6-Bromoimidazo[1,2-a]pyridin-3-yl)-1,3-thiazole 4.3 g 2-(1,1,1-tributylstannyl)-1,3-thiazole, 3.23 g <strong>[474706-74-6]6-bromo-3-iodoimidazo[1,2-a]pyridine</strong> (compound in Production Example 49) and 578 mg tetrakistriphenyl phosphine palladium were heated at 110C for 10 hours in xylene.. The solvent was removed, and the residue was purified by an NH silica gel column (solvent: hexane/dichloromethane/ethyl acetate) and recrystallized from ethyl acetate to give 2.06 g of the title compound as colorless crystals.1H-NMR (CDCl3) delta: 7.30(d, J=3.2Hz, 1H), 7.41(dd, J=9.6, 1.6Hz, 1H), 7.61(dd, J=9.6, 0.4Hz, 1H), 7.90 (d, J=3.2Hz, 1H), 8.12(s, 1H), 9.91(dd, J=1.6, 0.4Hz, 1H)

References: [1]Patent: EP1382603,2004,A1 .Location in patent: Page 61.

4
[ 6188-23-4 ]
[ 474706-74-6 ]

Yield	Reaction Conditions	Operation in experiment
96%	With N-iodo-succinimide; In acetonitrile; at 20℃; for 1h;	To a solution of 6-bromoimidazo[1,2-a]pyridine (721 mg 3.66 mmol) in 20 mL ACN were added 988 mg (4.39 mmol) of N-iodosuccinimide. The reaction was stirred at room temperature for 1 h. Solvent was removed in vacuo then residue was diluted with CH2Cl2 and washed successively with 10% NaOH aqueous solution, saturated thiosulfate solution and then with water. The organic layer was dried over magnesium sulfate and concentrated in vacuo to afford the desired product as a white solid (1.18 g), 96% yield, mp 209 C; IR (ATR) nu (cm-1) 3024. 1516. 711. 698. 1H NMR (400 MHz, CDCl3) delta 7.29 (dd, J=9.6, 1.8 Hz, 1H), 7.51 (d, J=9.6 Hz, 1H), 7.70 (s, 1H), 8.26-8.28 (m, 1H). 13C NMR (100.6 MHz, CDCl3) delta 61.4, 108.4, 118.6, 126.4, 128.6, 128.6, 141.1, 146.5. HRMS (EI) m/z calcd for C7H4BrIN2 [M+H]+: 322.8675, found: 322.8678.
77%	With N-iodo-succinimide; In acetonitrile; for 16.0833h;	To a slightly cloudy mixture of 6-bromoimidazo[l,2-alpha]pyridine (15.4 g, 78.0 mmol) in dry MeCN (500 mL) was added jV-iodosuccinimide (17.6 g, 78.0 mmol) portionwise over ~5 min (a precipitate immediately formed). After 16 h, the crude product was collected by filtration and triturated with boiling MeCN to provide 19.56 g (77%) of the title compound as an off-white solid. MS(ES)+ m/e 198.7 [M+H]+.
67%	With N-iodo-succinimide; In acetonitrile; at 20℃; for 5h;	Step: 1 To a solution of 6-bromoimidazo [l ,2-a]pyridine (20 g, 101.5 mmol) in ACN (300 mL) was added N-iodosuccinimide (22.8 g, 101.5 mmol) at rt and stirred for 5 h. The reaction mixture was filtered and washed with hot acetonitrile to afford 6-bromo-3-iodoimidazo[l,2- ajpyridine (22 g, 67%) as a pale yellow solid. 1H NMR (400 MHz, CDC13) delta 8.29 (s, 1H), 7.58 (d, J= 9.2 Hz, 1H), 7.35 (d, J= 7.6 Hz, 1H), 7.27 (s, 1H).

67%	With N-iodo-succinimide; In acetonitrile; at 20℃; for 5h;	To a solution of 6-bromoimidazo[1,2-a]pyridine (20 g, 101.5 mmol) in ACN (300 mL) was added N-iodosuccinimide (22.8 g, 101.5 mmol) at rt and stirred for 5 h. The reaction mixture was filtered and washed with hot acetonitrile to afford 6-bromo-3-iodoimidazo[1,2-a]pyridine (22 g, 67%) as a pale yellow solid. 1H NMR (400 MHz, CDCl3) delta 8.29 (s, 1H), 7.58 (d, J=9.2 Hz, 1H), 7.35 (d, J=7.6 Hz, 1H), 7.27 (s, 1H).
51%	With N-iodo-succinimide; In acetonitrile; at 20℃; for 1h;	To a solution of 6-bromoimidazo[1,2-a]pyridine (5 g, 25.4 mmol) in CH3CN (139 mL) was added NIS (6.85 g, 30.5 mmol). The reaction was stirred at r.t. for 1 hour and the reaction was concentrated. The residue was diluted with DCM (140 mL) and washed with 100 mL of 10 % NaOH, 100 mL of saturated thiosulfate solution, and then 100 mL of water. The organic layer was dried over MgSO4, filtered and concentrated. The material was isolated as a beige solid (4.163 g, 51 % yield).1H NMR (400 MHz, CDCl3) delta 8.28- 8.27 (m, 1H), 7.69 (s, 1H), 7.51 (dd, J = 1.2, 12.8 Hz, 1H), 7.29 (dd, J = 2.8, 12.8 Hz, 1H). This material had spectra that were indistinguishable from the literature.
		Production Example 49 6-Bromo-3-iodoimidazo[1,2-a]pyridine 10.7 g N-iodosuccinimide was added in divided portions to 100 ML solution of 9 g 6-bromoimidazo[1,2-a]pyridine in N,N-dimethylformamide, and the mixture was stirred for 2 hours.. An aqueous sodium thiosulfate solution was added thereto and stirred for 1 hour, water was added thereto, and the formed crystals were collected by filtration.. The product was recrystallized from tetrahydrofuran/ethanol to give 13.5 g of the title compound (colorless crystals).1H-NMR (CDCl3) delta: 7.29(dd, J=9.2, 2.0Hz, 1H), 7.51(dd, J=9.2, 0.8Hz, 1H), 7.70 (s, 1H), 8.28(dd, J=2.0, 0.8Hz, 1H)
	With iodine; sodium acetate; In methanol; at 0 - 20℃;	(2) 6-bromo-3-iodoimidazo[ 1 ,2-a]pyridine.; To a 150 mL round bottomed flask was added 6-bromoimidazo[l,2-a]pyridine (5.00 g, 25.4 mmol), anhydrous sodium acetate (5.69 g, 69.4 mmol) and MeOH (60 mL). The resulting mixture was cooled to 0 0C followed by adding iodine (7.13 g, 28.1 mmol). After the addition, ice bath was removed. It was warmed up to rt and continued to stir for 20 h. The precipitate in the reaction mixture was collected by filtration. The precipitate was washed with MeOH and dried to afford the desired product as light grey solid (7.0 g). MS (ESI pos. ion) m/z: 322.8. Calcd exact mass for C7H4BrIN2: 321.9. 1H NMR (300 MHz, CHLOROFORM-J) delta ppm 7.30 (d, J=10.82 Hz, 1 H) 7.52 (d, J=9.50 Hz, 1 H) 7.71 (s, 1 H) 8.29 (s, 1 H).
	With N-iodo-succinimide; In acetonitrile; at 20℃; for 3h;	Step 2: Preparation of 6-bromo-3-iodoimidazo[l,2-a]pyridineTo a solution of 6-bromoimidazo[l,2-a]pyridine (10 g, 51 mmol) in MeCN (100 ml) was added N-iodosuccinimide (10.6 g 61.0 mmol). The reaction was stirred at ambient temperature for 3 h, after which the volatiles were removed in vacuo. The residue thus obtained was dissolved in EA (300 ml) and washed successively with 10% aqueous sodium hydroxide solution (100 ml), saturated aqueous thiosulfate solution (100 ml), and water (100 ml). The organic layer was then dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel, eluting with 5%-10% EA in PE) to afford 6-bromo-3-iodoimidazo[l,2-a]pyridine. MS (ESI) Calc'd for (C7H5BrIN2) [M+H]+, 323, 325; found, 323, 325.

References: [1]Tetrahedron,2011,vol. 67,p. 7128 - 7138.
[2]Journal of Medicinal Chemistry,2011,vol. 54,p. 2455 - 2466.
[3]Patent: WO2008/14219,2008,A2 .Location in patent: Page/Page column 45.
[4]Patent: WO2013/147711,2013,A1 .Location in patent: Page/Page column 248.
[5]Patent: US2014/371199,2014,A1 .Location in patent: Paragraph 0852.
[6]Patent: WO2017/197151,2017,A1 .Location in patent: Page/Page column 41.
[7]Patent: EP1382603,2004,A1 .Location in patent: Page 57; 58.
[8]Patent: WO2010/108074,2010,A2 .Location in patent: Page/Page column 53-54.
[9]Patent: WO2015/188369,2015,A1 .Location in patent: Page/Page column 88; 89.

5
[ 474706-74-6 ]
[ 171364-80-0 ]
[ 474706-76-8 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate;tetrakis(triphenylphosphine) palladium(0); In DMF (N,N-dimethyl-formamide); at 100℃;	Production Example 51 methyl 4-(6-bromoimidazo[1,2-a]pyridin-3-yl)benzoate 2.3 g methyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate prepared according to T. Ishiyama et al., J. Org. Chem., 60, 7508 (1995), 2.0 g <strong>[474706-74-6]6-bromo-3-iodoimidazo[1,2-a]pyridine</strong> (compound in Production Example 49), 2. 5 g potassiumphosphate, 360 mg tetrakistriphenyl phosphine palladium and 30 ML N, N-dimethylformamide were heated at 100C under nitrogen atmosphere.. Insolubles were filtered off, the solvent was removed, and the residue was purified by NH silica gel column chromatography (hexane/ethyl acetate) and recrystallized from ethyl acetate to give 1.39 g of the title compound (colorless crystals).1H-NMR (CDCl3) delta: 3.97(s, 3H), 7.32(dd, J=9.6, 2.0Hz, 1H), 7.62(d, J=9.6Hz, 1H), 7.65(dt, J=8.8, 2.0Hz, 2H), 7.79(br.s, 1H), 8.21(dt, J=8.8, 2.0Hz, 2H), 8.50(br.s, 1H)

References: [1]Patent: EP1382603,2004,A1 .Location in patent: Page 58.

6
[ 474706-74-6 ]
[ 474706-72-4 ]
[ 474706-89-3 ]

Yield	Reaction Conditions	Operation in experiment
		Production Example 58 6-Bromo-3-[5-(methylsulfanyl)-2-thienyl]imidazo[1,2-a]pyridine 2 g of the title compound was obtained as a yellow oil from 4.65 g tributyl[5-(methylsulfanyl)-2-thienyl]stannane (compound in Production Example 46) and 3.10 g <strong>[474706-74-6]6-bromo-3-iodoimidazo[1,2-a]pyridine</strong> (compound in Production Example 49).1H-NMR (CDCl3) delta: 2.57(s, 3H), 7.13(d, J=3.6Hz, 1H), 7.15(d, J=3.6Hz, 1H), 7.29(dd, J=9. 6, 1. 6Hz, 1H), 7.56 (dd, J=9.6, 0.8Hz, 1H), 7.72(s, 1H), 8.49(dd, J=1.6, 0.8Hz, 1H)

References: [1]Patent: EP1382603,2004,A1 .Location in patent: Page 61.

7
[ 474706-74-6 ]
[ 474706-77-9 ]

Yield	Reaction Conditions	Operation in experiment
		Production Example 52 4-(6-Bromoimidazo[1,2-a]pyridin-3-yl)benzamide 228 mg of the title compound was obtained as colorless crystals in the same manner as in Production Example 51 from 1.31 g 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide and 1 g <strong>[474706-74-6]6-bromo-3-iodoimidazo[1,2-a]pyridine</strong> (compound in Production Example 49).1H-NMR (CDCl3) delta: 5.75(br.s, 1H), 6.18(br.s, 1H), 7.31(dd, J=9. 6, 1.6Hz, 1H), 7.61(d, J=9. 6Hz, 1H), 7.66(d, J=8.8, 2H), 7.76(s, 1H), 7.99(d, J=8.8, 2H), 8.47(dd, J=1.6, 0.4Hz, 1H)

References: [1]Patent: EP1382603,2004,A1 .Location in patent: Page 59.

8
[ 474706-74-6 ]
[ 474709-70-1 ]

Yield	Reaction Conditions	Operation in experiment
		Production Example 304 ethyl 4-(6-bromoimidazo[1,2-a]pyridin-3-yl)-2-fluorobenzoate From 4.4g of ethyl 2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate prepared from ethyl 4-bromo-2-fluorobenzoate by a method of T. Ishiyama et al., J. Org. Chem., 60, 7508 (1995) and 3.2 g of <strong>[474706-74-6]6-bromo-3-iodoimidazo[1,2-a]pyridine</strong> (compound in Production Example 49), 1.6 g of the title compound (colorless crystals) was obtained by the same method as in Production Example 51.1H-NMR (CDCl3) delta: 1.44(t, J=7.2Hz, 3H), 4.44(q, J=7.2Hz, 2H), 7.34(dd, J=9.6, 1. 6Hz, 1H), 7.35(dd, J=11.6, 1. 6Hz, 2H), 7.62(dd, J=9.6, 0.8Hz, 1H), 7.80(s, 1H), 8.12(dd, J=8.0, 8.0Hz, 1H), 8.50(dd, J=1.6, 0.8Hz, 1H)

References: [1]Patent: EP1382603,2004,A1 .Location in patent: Page 156.

9
[ 474706-74-6 ]
[ 214360-51-7 ]
[ 474706-78-0 ]

Yield	Reaction Conditions	Operation in experiment
		Production Example 53 4-(6-Bromoimidazo[1,2-a]pyridin-3-yl)-1-benzene sulfonamide 187 mg of the title compound was obtained as colorless crystals (recrystallized from ethyl acetate/methanol) from 900 mg 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzene sulfonamide and 646 mg <strong>[474706-74-6]6-bromo-3-iodoimidazo[1,2-a]pyridine</strong> (compound in Production Example 49). MS m/e (ESI) 352 (MH+)

References: [1]Patent: EP1382603,2004,A1 .Location in patent: Page 59.

10
[ 474706-74-6 ]
[ 541-41-3 ]
[ 372198-69-1 ]

Yield	Reaction Conditions	Operation in experiment
		Production Example 275 ethyl 6-bromoimidazo[1,2-a]pyridine-3-carboxylate A mixture of 9.69 g <strong>[474706-74-6]6-bromo-3-iodoimidazo[1,2-a]pyridine</strong> (compound in Production Example 49) and 450 ML anhydrous tetrahydrofuran was added little by little to 4.5 ML isopropyl magnesium bromide (0.75 M tetrahydrofuran solution) under ice-cooling in a stream of nitrogen.. Then, this reaction solution was returned to room temperature and stirred for 1.5 hours.. The reaction solution was cooled to -60C or less in a dry ice/acetone bath, 50 ML solution of 4.5 ML ethyl chlorocarbonate in anhydrous tetrahydrofuran was added dropwise thereto over 30 minutes, and the temperature of the reaction solution was increased to 0C. After saturated sodium bicarbonate was added to the reaction solution, ethyl acetate and water were added thereto, andthe organic layer was separated.. The aqueous layer was saturated with common salt and then extracted with ethyl acetate.. The combined organic layer was washed with brine and then dried over anhydrous sodium sulfate.. The drying agent was filtered off, and the filtrate was evaporated.. The resulting residue was purified by NH silica gel column chromatography (ethyl acetate/hexane) to give 5.09 g of the title compound as white crystals.1H-NMR (CDCl3) delta: 1.43(t, J=7.2Hz, 3H), 4.43(q, J=7.2Hz, 2H), 7.49(dd, J=9.2, 2.0Hz, 1H), 7.63(dd, J=9.2, 0,8Hz, 1H), 8.27(s, 1H), 9.49(dd, J=2.0, 0.8Hz, 1H)

References: [1]Patent: EP1382603,2004,A1 .Location in patent: Page 144.

11
[ 474706-74-6 ]
[ 5720-07-0 ]
[ 474706-75-7 ]

Yield	Reaction Conditions	Operation in experiment
		Production Example 50 6-Bromo-3-(4-methoxyphenyl)imidazo[1,2-a]pyridine 0.81 ML 1, 3-propane diol was added to a suspension of 1. 69 g 4-methoxyphenylboronic acid in 15 ML diethyl ether, and the mixture was stirred a room temperature for 1 hour.. Formed water was removed, and the organic solvent was evaporated, whereby an oil was obtained. 2.7 g <strong>[474706-74-6]6-bromo-3-iodoimidazo[1,2-a]pyridine</strong> (compound in Production Example 49), 3.5 g potassium phosphate, 483 mg tetrakistriphenyl phosphine palladium and 40 ML N, N-dimethylformamide were added thereto and heated at 90C for 3 hours under nitrogen atmosphere.. Insolubleswere filtered off, the solvent was removed, and the residue was purified by NH silica gel column chromatography (hexane/ethyl acetate) to give 2 g of the title compound as an oil.1H-NMR (CDCl3) delta: 3.89(s, 3H), 7.07(dt, J=8.8, 2.0Hz, 2H), 7.25(dd, J=9.2, 1. 6Hz, 1H), 7.45(dt, J=8.8, 2.0Hz, 2H), 7.59(dd, J=9.2, 0.8Hz, 1H), 7.63(s, 1H), 7.98(dd, J=1.6, 0.8Hz, 1H) MS m/e (ESI)303(MH+)

References: [1]Patent: EP1382603,2004,A1 .Location in patent: Page 58.

12
[ 474706-74-6 ]
[ 1083168-92-6 ]
[ 1246184-32-6 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium acetate;bis[di-t-butyl(p-dimethylaminophenyl)phosphino]palladium (II) Dichloride; In water; butan-1-ol; at 100℃; for 20h;Inert atmosphere;	(3) 6-Bromo-3-(5,6-dimethoxy-3-pyridinyl)imidazo[l,2-a]pyridine.; To a 100 rnL round bottomed flask was added 2,3-dimethoxy-5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan- 2-yl)pyridine (0.80 g, 3.02 mmol, prepared from the corresponding bromide), 6-bromo-3- iodoimidazo[l,2-a]pyridine (1.17 g, 3.62 mmol), A-phos (Bis[(di-tert-butylphenyl phosphine)]palladium dichloride) (0.094 g, 0.15 mmol), potassium acetate (0.74 g, 7.54 mmol), water (1.5 mL), and 1-butanol (15 mL). The reaction was then heated at 100 0C under N2 for 20 h. After cooled to rt, the 1 -butanol was concentrated. The residue was partitioned between water/CHCl3. The organic layer was dried over MgSO4 and concentrated. The crude product was purified using SiO2 chromatography (Teledyne Isco RediSep, 12 g SiO2 catridge, methylene chloride/ethyl acetate/methanol = 55% /43%/2%, Flow = 30 niL/min). A peak at 18 min was collected. The solvent was removed in vacuo to afford the desired product as brown solid (450 mg). MS (ESI pos. ion) m/z: 333.9. Calcd exact mass for Ci4Hi2BrN3O2: 333.0. 1U NMR (300 MHz, CHLOROFORM-^) delta ppm 3.95 (s, 3 H) 4.11 (s, 3 H) 7.14 (s, 1 H) 7.31 (d, J=9.50 Hz, 1 H) 7.63 (d, J=9.50 Hz, 1 H) 7.69 (s, 1 H) 7.94 (s, 1 H) 8.35 (s, 1 H).

References: [1]Patent: WO2010/108074,2010,A2 .Location in patent: Page/Page column 53-54.

13
[ 474706-74-6 ]
N-(2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)dimethylaminosulfonamide [ No CAS ]
[ 1246184-54-2 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; at 110℃; for 0.25h;microwave irradiation; sealed tube;	EXAMPLE 18; N-(2-Chloro-5-(6-(pyridin-4-yl)imidazo[l ,2-a]pyridin-3-yl)pyridin-3- yl)dimethylaminosulfonamide; (l) N-(5-(6-bromoimidazo[l,2-a]pyridin-3-yl)-2-chloropyridin-3- yl)dimethylaminosulfonamide.; To a 5 mL microwave tube was added N-(2-chloro-5-(4,4,5,5- tetramethyl-l,3,2-dioxaborolan-2-yl)pyridin-3-yl)dimethylaminosulfonamide (0.200 g, 0.553 mmol),6-bromo-3-iodoimidazo[l,2-a]pyridine (0.214 g, 0.664 mmol), 1,1'- bis(diphenylphosphino)ferrocene]dichloride palladium(II) (0.020 g, 0.028 mmol), sodium carbonate (0.691 mL, 1.383 mmol), and dioxane (3 mL). The resulting mixture was sealed and underwent microwave heating at 110 0C for 15 min. The solvent was removed. The residue was partitioned between pH 7 buffer (IM TRIS-HCL) and DCM. The aqueous layer was extracted more with DCM (2 x 10 mL). The combined organic layers were dried over MgSO4 and concentrated. The crude product was purified using SiO2 chromatography (Teledyne Isco RediSep, 12 g SiO2, hexanes:acetone=80%:20%, Flow = 30 mL/min). The solvent was removed in vacuo to afford the desired product as brown solid (180 mg). MS (ESI pos. ion) m/z: 429.7. Calcd exact mass for Ci4Hi3BrClN5O2S: 428.9. 1U NMR (300 MHz, CHLOROFORM-J) delta ppm 2.94 (s, 6 H) 7.36 (d, J=9.65 Hz, 1 H) 7.63 (d, J=9.50 Hz, 1 H) 7.79 (s, 1 H) 8.09 (s, 1 H) 8.34 (s, 1 H) 8.42 (s, 1 H).

References: [1]Patent: WO2010/108074,2010,A2 .Location in patent: Page/Page column 61.

14
[ 1072-97-5 ]
[ 474706-74-6 ]

References: [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 2455 - 2466.
[2]Tetrahedron,2011,vol. 67,p. 7128 - 7138.
[3]Patent: WO2015/188369,2015,A1 .

15
[ 474706-74-6 ]
[ 1276110-19-0 ]

References: [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 2455 - 2466.

16
[ 474706-74-6 ]
C₁₇H₁₃N₅ [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 2455 - 2466.

17
[ 474706-74-6 ]
[ 1692-25-7 ]
[ 1276109-83-1 ]

References: [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 2455 - 2466.

18
[ 474706-74-6 ]
[ 107-19-7 ]
[ 1332703-46-4 ]

Yield	Reaction Conditions	Operation in experiment
92%	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; In N,N-dimethyl-formamide; at 20℃; for 3h;Inert atmosphere;	General procedure: To a solution of <strong>[474706-74-6]6-bromo-3-iodoimidazo[1,2-a]pyridine</strong> (14 or 16) (14: 100 mg or 16: 81 mg, 0.250 mmol) in 2 mL of a mixture of DMF/Et3N (1/1, v/v) were successively added the desired alkyne (0.501 mmol), copper iodide (0.050 mmol) and 8.7 mg (0.012 mmol) of bis(triphenylphosphine)palladium dichloride. The reaction was stirred at room temperature sealed under argon. Once TLC indicated complete consumption of starting material (3 h), the reaction was quenched with water and extracted with dichloromethane (2×15 mL). The combined organic layer were dried over magnesium sulfate and concentrated in vacuo. The resulting residue was purified by column chromatography on silica gel (EtOAc/PE) to afford the corresponding cross-coupling products 15, 17-20, and 22-24.

References: [1]Tetrahedron,2011,vol. 67,p. 7128 - 7138.

19
[ 474706-74-6 ]
[ 536-74-3 ]
[ 1332703-47-5 ]

Yield	Reaction Conditions	Operation in experiment
96%	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; In N,N-dimethyl-formamide; at 20℃; for 3h;Inert atmosphere;	General procedure: To a solution of <strong>[474706-74-6]6-bromo-3-iodoimidazo[1,2-a]pyridine</strong> (14 or 16) (14: 100 mg or 16: 81 mg, 0.250 mmol) in 2 mL of a mixture of DMF/Et3N (1/1, v/v) were successively added the desired alkyne (0.501 mmol), copper iodide (0.050 mmol) and 8.7 mg (0.012 mmol) of bis(triphenylphosphine)palladium dichloride. The reaction was stirred at room temperature sealed under argon. Once TLC indicated complete consumption of starting material (3 h), the reaction was quenched with water and extracted with dichloromethane (2×15 mL). The combined organic layer were dried over magnesium sulfate and concentrated in vacuo. The resulting residue was purified by column chromatography on silica gel (EtOAc/PE) to afford the corresponding cross-coupling products 15, 17-20, and 22-24.

References: [1]Tetrahedron,2011,vol. 67,p. 7128 - 7138.

20
[ 474706-74-6 ]
[ 115-19-5 ]
[ 1332703-45-3 ]

Yield	Reaction Conditions	Operation in experiment
95%	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; In N,N-dimethyl-formamide; at 20℃; for 3h;Inert atmosphere;	General procedure: To a solution of <strong>[474706-74-6]6-bromo-3-iodoimidazo[1,2-a]pyridine</strong> (14 or 16) (14: 100 mg or 16: 81 mg, 0.250 mmol) in 2 mL of a mixture of DMF/Et3N (1/1, v/v) were successively added the desired alkyne (0.501 mmol), copper iodide (0.050 mmol) and 8.7 mg (0.012 mmol) of bis(triphenylphosphine)palladium dichloride. The reaction was stirred at room temperature sealed under argon. Once TLC indicated complete consumption of starting material (3 h), the reaction was quenched with water and extracted with dichloromethane (2×15 mL). The combined organic layer were dried over magnesium sulfate and concentrated in vacuo. The resulting residue was purified by column chromatography on silica gel (EtOAc/PE) to afford the corresponding cross-coupling products 15, 17-20, and 22-24.

References: [1]Tetrahedron,2011,vol. 67,p. 7128 - 7138.

21
[ 474706-74-6 ]
[ 627-41-8 ]
[ 1332703-44-2 ]

Yield	Reaction Conditions	Operation in experiment
96%	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; In N,N-dimethyl-formamide; at 20℃; for 3h;Inert atmosphere;	General procedure: To a solution of <strong>[474706-74-6]6-bromo-3-iodoimidazo[1,2-a]pyridine</strong> (14 or 16) (14: 100 mg or 16: 81 mg, 0.250 mmol) in 2 mL of a mixture of DMF/Et3N (1/1, v/v) were successively added the desired alkyne (0.501 mmol), copper iodide (0.050 mmol) and 8.7 mg (0.012 mmol) of bis(triphenylphosphine)palladium dichloride. The reaction was stirred at room temperature sealed under argon. Once TLC indicated complete consumption of starting material (3 h), the reaction was quenched with water and extracted with dichloromethane (2×15 mL). The combined organic layer were dried over magnesium sulfate and concentrated in vacuo. The resulting residue was purified by column chromatography on silica gel (EtOAc/PE) to afford the corresponding cross-coupling products 15, 17-20, and 22-24.

References: [1]Tetrahedron,2011,vol. 67,p. 7128 - 7138.

22
[ 474706-74-6 ]
[ 1679-18-1 ]
[ 1464158-49-3 ]

Yield	Reaction Conditions	Operation in experiment
52%	With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 90℃; for 6h;Inert atmosphere;	Step 2: A mixture of 6-bromo-3-iodoimidazo[l,2-a]pyridine (21 g, 65.4 mmol), 4- chlorophenylboronic acid (11.22 g, 71.9 mmol), K3P04 (27.7g, 130.8 mmol) in DMF (100 mL), and water (15 mL) was degassed with argon for 30 min. Pd(PPh3)4 (3.77 g, 3.27 mmol) was added and again degassed with argon for 30 min and the reaction mixture was heated at 90 C for 6 h. TLC indicated absence of SM and formation of two polar spots. Water (2x100 ml) was added to the reaction mixture to induce precipitation which was filtered to give crude product. The crude product was purified by column chromatography (silica gel, eluent (CHCl3/MeOH 95:5) to afford 6-bromo-3-(4-chlorophenyl)imidazo[l,2- a]pyridine (10.6 g, 52%) as a yellowish green solid. 1H NMR (400 MHz, CDC13) delta 8.38 (s, 1H), 7.69 (s, lH), 7.60 (d, J= 8.0 Hz, 2H), 7.82 (t, J= 9.2 Hz, 1H), 7.58 (q, J= 5.2 Hz, 4H), MS (ESI) m/z 309 [C13H8BrN2Cl + 2H ]+
52%	With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 90℃; for 6h;Inert atmosphere;	To a solution of <strong>[474706-74-6]6-bromo-3-iodoimidazo[1,2-a]pyridine</strong> (21 g, 65.4 mmol), 4-Chlorophenylboronic acid (11.22 g, 71.9 mmol), K3PO4 (27.7 g, 130.8 mmol) in a mixture of DMF (100 mL) and water (15 mL), was added Pd(PPh3)4 (3.77 g, 3.27 mmol). The reaction mixture was heated at 90 C. for 6 h under argon atmosphere prior to the addition of water (200 mL). The precipitate was isolated by filtration and was purified by column chromatography (silica gel, eluent CHCl3/MeOH 95:5) to afford of 6-bromo-3-(4-chlorophenyl)imidazo[1,2-a]pyridine (10.6 g, 52%) as a yellowish green solid. 1H NMR (400 MHz, CDCl3) delta 8.38 (s, 1H), 7.69 (s, 1H), 7.60 (d, J=8.0 Hz, 2H), 7.82 (t, J=9.2 Hz, 1H), 7.58 (q, J=5.2 Hz, 4H), MS (ESI) m/z 309 [C13H8BrN2Cl+2H]+.

References: [1]Patent: WO2013/147711,2013,A1 .Location in patent: Page/Page column 248.
[2]Patent: US2014/371199,2014,A1 .Location in patent: Paragraph 0629.

23
[ 474706-74-6 ]
[ 1464155-68-7 ]