689291-89-2|5-Bromo-2-iodobenzaldehyde| Ambeed

Structure of 689291-89-2

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Quality Control of [ 689291-89-2 ] Purity: 98% SDS Specification

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Product Details of [ 689291-89-2 ]

CAS No. :	689291-89-2
Formula :	C₇H₄BrIO
M.W :	310.92
SMILES Code :	BrC1=CC(=C(C=C1)I)C=O
MDL No. :	MFCD07779026
Boiling Point :	No data available
InChI Key :	MOELYMOGQIDKNW-UHFFFAOYSA-N
Pubchem ID :	21973861

Safety of [ 689291-89-2 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H315-H319-H335-H413
Precautionary Statements:	P261-P273-P305+P351+P338

Computational Chemistry of [ 689291-89-2 ] Show Less

Physicochemical Properties

Num. heavy atoms	10
Num. arom. heavy atoms	6
Fraction Csp3	0.0
Num. rotatable bonds	1
Num. H-bond acceptors	1.0
Num. H-bond donors	0.0
Molar Refractivity	52.25
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	17.07 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.03
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	2.73
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.87
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.	3.08
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	3.63
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.87

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-3.87
Solubility	0.0424 mg/ml ; 0.000136 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-2.74
Solubility	0.562 mg/ml ; 0.00181 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	-4.13
Solubility	0.0229 mg/ml ; 0.0000738 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Moderately 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	Yes
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.	-6.26 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	1.0
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	2.0 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)	1.92

Application In Synthesis of [ 689291-89-2 ]

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

Downstream synthetic route of [ 689291-89-2 ]

[ 689291-89-2 ] Synthesis Path-Downstream 1~35

1
[ 689291-89-2 ]
[ 75-64-9 ]
[ 689291-90-5 ]

Yield	Reaction Conditions	Operation in experiment
100%	In tetrahydrofuran; at 20℃; for 96h;Inert atmosphere;	Intermediate 21; N-[(l£)-(5-bromo-2-iodophenyI)methylidene]-2-methyl-2- ropanamine; To a solution of 2-1, 4-Br benzaldehyde (2.0 g, 6.4 mmol) in anhydrous THF (10 mL) was added tert-butylamine (2.0 mL, 19.3 mmol) and the reaction stirred at room temperature under a nitrogen atmosphere for 4 days. The reaction was concentrated in vacuo and partitioned between dichloromethane and water. The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo to afford the desired compound as a pale yellow solid in quantitative yield.
	In tetrahydrofuran; at 20℃; for 40h;	The product from Example 62C (2.28 g, 7.3 mmol) in THF (10 ML) was treated with t-butylamine (1.61 g, 22.0 mmol) and stirred under nitrogen at room temperature for 40 hours.The mixture was concentrated under reduced pressure and the residue was dissolved in 30 ML of methylene chloride.The methylene chloride was washed with 10 ML water and concentrated to provide the title compound which was used in the next step without further purification. 1H NMR (CDCl3, 400 MHz) δ 8.29 (s, 1H), 8.05 (d, J=4 Hz, 1H), 7.66 (d, J=8 Hz, 1H), 7.19 (dd, J=4, 8 Hz, 1H), 1.34 (s, 9H). MS (DCl/NH3) 366 [M+H]+.
	In tetrahydrofuran; at 20℃; for 40h;	The product from Example 15C (2.28 g, 7.3 mmol) in THF (10 mL) was treated with t-butylamine (1.61 g, 22.0 mmol) and stirred under nitrogen at room temperature for 40 hours. The mixture was concentrated under reduced pressure and the residue was dissolved in 30 mL of methylene chloride. The methylene chloride was washed with 10 mL water and concentrated to provide the title compound which was used in the next step without further purification. 1H NMR (CDCl3, 400 MHz) δ 8.29 (s, 1H), 8.05 (d, J=4 Hz, 1H), 7.66 (d, J=8 Hz, 1H), 7.19 (dd, J=4, 8 Hz, 1H), 1.34 (s, 9H). MS (DCl/NH3) 366 [M+H]+.

	In tetrahydrofuran; at 20℃; for 40h;	Example 15D N-[(1E)-(5-Bromo-2-iodophenyl)methylene]-N-(tert-butyl)amine The product from Example 15C (2.28 g, 7.3 mmol) in THF (10 mL) was treated with t-butylamine (1.61 g, 22.0 mmol) and stirred under nitrogen at room temperature for 40 hours. The mixture was concentrated under reduced pressure and the residue was dissolved in 30 mL of methylene chloride. The methylene chloride was washed with 10 mL water and concentrated to provide the title compound which was used in the next step without further purification. 1H NMR (CDCl3, 400 MHz) δ 8.29 (s, 1H), 8.05 (d, J=4 Hz, 1H), 7.66 (d, J=8 Hz, 1H), 7.19 (dd, J=4, 8 Hz, 1H), 1.34 (s, 9H). MS (DCl/NH3) 366 [M+H]+.
	In tetrahydrofuran; at 20℃; for 40h;Inert atmosphere;	To a stirred solution of <strong>[689291-89-2]5-bromo-2-iodobenzaldehyde</strong> (4.2 g, 13.5 mmol, 1 .0 equiv) in THF (20 ml_) was added t-butyl amine (4.26 ml_, 40.6 mmol, 3.0 equiv) at room temperature, under nitrogen atmosphere. The reaction mixture was stirred for 40 h at room temperature and evaporated under vacuum to obtain a residue. The residue was dissolved in DCM (100 ml_) washed with H20 (50 ml_), dried over sodium sulphate and evaporated to obtain (£)-/V-(5-bromo-2-iodobenzylidene)-2-methylpropan-2-amine (3.0 g, crude) as a yellow oily compound. 1H NMR (400 MHz, CDCI3) δ ppm 1 .32 (s, 9H), 7.20 (dd, J=2.8, 8.4 Hz, 1 H), 7.68 (d, J=8.4 Hz, 1 H), 8.07 (d, J=2.4 Hz, 1 H), 8.31 (s, 1 H).

References: [1]Patent: WO2011/91446,2011,A1 .Location in patent: Page/Page column 10; 25.
[2]Patent: US2004/92521,2004,A1 .Location in patent: Page/Page column 19-20; 46-47.
[3]Patent: US2005/256118,2005,A1 .Location in patent: Page/Page column 18-19.
[4]Patent: US2005/256309,2005,A1 .Location in patent: Page/Page column 20; 21; 36.
[5]Patent: US2005/272728,2005,A1 .Location in patent: Page/Page column 19-20.
[6]Patent: US2005/272736,2005,A1 .Location in patent: Page/Page column 20-21; 36.
[7]Patent: WO2018/15879,2018,A1 .Location in patent: Page/Page column 82.

2
[ 199786-58-8 ]
[ 689291-89-2 ]

Yield	Reaction Conditions	Operation in experiment
98%	With dipyridinium dichromate; In dichloromethane; at 20℃; for 4h;Inert atmosphere;	To a stirred solution of PDC (11.0 g, 0.0288 mol) in CH2Cl2 (60 mL) was added a solution of 11 (4.50 g, 0.0144 mol) in CH2Cl2 (20 mL). The mixed content was stirred for 4 h at rt. The solvent was then removed under vacuum to give the crude product of 12, which was purified by silica flash column chromatography (hexanes/CH2Cl2, 7:3) to give compound 12 (4.40 g, 0.0142 mol, 98%) as a white solid.
93%	With oxalyl dichloride; dimethyl sulfoxide; triethylamine; In dichloromethane; at -70 - -10℃; for 1.25h;Inert atmosphere;	A solution of oxalyl chloride (1 .99 mL, 23.04 mmol, 1 .6 equiv) in DCM (25 mL) was cooled to -70C and DMSO (2.44 mL, 34.5 mmol, 2.4 equiv) in DCM (25 mL) was added at -65C to -70C. The reaction mixture stirred for 10 minutes under nitrogen atmosphere at - 70C and then (5-bromo-2-iodophenyl)methanol (4.55 g, 14.4 mmol, 1 .0 equiv) in DCM (100 mL) was added. The reaction mixture was stirred at -65C for 15 minutes and triethylamine (10 mL, 72 mmol, 5.0 equiv) was added. The reaction mixture was allowed to warm to -10C and stir for 1 h. Water (40 mL) was added and the reaction mixture was allowed to warm to room temperature. The organic layer was separated and evaporated to obtain 5-bromo-2-iodobenzaldehyde (4.2 g, 93 %) as white solid. 1H NMR (400 MHz.CDCb) δ ppm 7.45 (d, J=7.6 Hz, 1 H), 7.81 (d, J=1 1 .6 Hz, 1 H), 7.98 (d, J=1 .6 Hz, 1 H), 9.97 (s, 1 H).
		A solution of oxalyl chloride (1.53 g, 0.012 mol) in CH2Cl2 (15 ML) was cooled to -70 C., and DMSO (1.41 g, 0.018 mol) in CH2Ck (15 ML) was added at -65 to -70 C. The mixture was stirred under nitrogen for 10 minutes at -70 C. and then treated with the product from Example 62B (2.35 g, 7.5 mmol) in 60 ML CH2Cl2.The slurry was stirred at -65 C. for 15 minutes and treated with triethylamine (3.8 g, 0.037 mol).The mixture was allowed to warm to -10 C. over 1 hour.The mixture was treated with 20 ML of water and allowed to warm to room temperature.The organic layer was separated and concentrated to provide the title compound. 1H NMR (CDCl3, 400 MHz) δ 9.97 (s, 1H), 7.97 (d, J=4 Hz, 1H), 7.79 (d, J=8 Hz, 1H), 7.40 (dd, J=4, 8 Hz, 1H). MS (DCl/NH3) [M+NH4]+ at 328.

	With oxalyl dichloride; dimethyl sulfoxide; triethylamine; In dichloromethane; at -70 - -10℃; for 1.25h;	A solution of oxalyl chloride (1.53 g, 0.012 mol) in CH2Cl2 (15 mL) was cooled to -70 C., and DMSO (1.41 g, 0.018 mol) in CH2Cl2 (15 mL) was added at -65 to -70 C. The mixture was stirred under nitrogen for 10 minutes at -70 C. and then treated with the product from Example 15B (2.35 g, 7.5 mmol) in 60 mL CH2Cl2. The slurry was stirred at -65 C. for 15 minutes and treated with triethylamine (3.8 g, 0.037 mol). The mixture was allowed to warm to -10 C. over 1 hour. The mixture was treated with 20 mL of water and allowed to warm to room temperature. The organic layer was separated and concentrated to provide the title compound. 1H NMR (CDCl3, 400 MHz) δ 9.97 (s, 1H), 7.97 (d, J=4 Hz, 1H), 7.79 (d, J=8 Hz, 1H), 7.40 (dd, J=4, 8 Hz, 1H). MS (DCl/NH3) [M+NH4]+ at 328.
		Example 15C 5-Bromo-2-iodobenzaldehyde A solution of oxalyl chloride (1.53 g, 0.012 mol) in CH2Cl2 (15 mL) was cooled to -70 C., and DMSO (1.41 g, 0.018 mol) in CH2Cl2 (15 mL) was added at -65 to -70 C. The mixture was stirred under nitrogen for 10 minutes at -70 C. and then treated with the product from Example 15B (2.35 g, 7.5 mmol) in 60 mL CH2Cl2. The slurry was stirred at -65 C. for 15 minutes and treated with triethylamine (3.8 g, 0.037 mol). The mixture was allowed to warm to -10 C. over 1 hour. The mixture was treated with 20 mL of water and allowed to warm to room temperature. The organic layer was separated and concentrated to provide the title compound. 1H NMR (CDCl3, 400 MHz) δ 9.97. (s, 1H), 7.97 (d, J=4 Hz, 1H), 7.79 (d, J=8 Hz, 1H), 7.40 (dd, J=4, 8 Hz, 1H). MS (DCl/NH3) [M+NH4]+ at 328.
	With dipyridinium dichromate; In dichloromethane; at 20℃; for 4h;	The compound was synthesized according to the published procedure. [Zhou, N.; Wang, L.; Thompson, D. W.; Zhao, Y. Org. Lett. 2008, 10 (14), 3001-3004] Compound L15 and pyridinium dichromate (7.2 g, 19.2 mmol, 2 eq.) were dissolved in dry dichloromethane (40 ml) and the mixture was stirred at room temperature for 4 hours. The mixture was filtered through celite, washed with diethyl ether and solvents were evaporated. The solid was adsorbed on silica gel in a mixture of cyclohexane/acetone and it was purified by flash column chromatography on silica gel (cyclohexane to 20% ethyl acetate modified with 10% methanol (v/vi)), yielded 2.3 g (77%) of the title compound as a white solid (85% NMR purity). 1H NMR (401 MHz, Chloroform-d) δ 9.99 (s, 1H), 7.99 (d, J= 2.5 Hz, 1H), 7.81 (d, J= 8.4 Hz, 1H), 7.41 (dd, J= 8.4, 2.5 Hz, 1H). 13C NMR (101 MHz, Chloroform-d) δ 194.45, 141.95, 138.37, 136.47, 133.24, 123.63, 98.39. MS (CI-QMS) m/z: [M + H]+ calcd for C7H5BrIO, 310.9; found, 310.9.

References: [1]Organic Letters,2008,vol. 10,p. 3001 - 3004.
[2]Tetrahedron,2011,vol. 67,p. 125 - 143.
[3]Organic Letters,2016,vol. 18,p. 2126 - 2129.
[4]Journal of Organic Chemistry,2020,vol. 85,p. 9161 - 9178.
[5]Patent: WO2018/15879,2018,A1 .Location in patent: Page/Page column 81-82.
[6]Patent: US2004/92521,2004,A1 .Location in patent: Page/Page column 19-20; 46.
[7]Patent: US2005/256118,2005,A1 .Location in patent: Page/Page column 18-19.
[8]Patent: US2005/256309,2005,A1 .Location in patent: Page/Page column 20; 21; 36.
[9]Patent: US2005/272728,2005,A1 .Location in patent: Page/Page column 19-20.
[10]Patent: US2005/272736,2005,A1 .Location in patent: Page/Page column 20; 36.
[11]Chemical Communications,2013,vol. 49,p. 3254 - 3256.
[12]Journal of the American Chemical Society,2018,vol. 140,p. 9400 - 9403.
[13]Organic Letters,2020,vol. 22,p. 7261 - 7266.
[14]Patent: WO2021/83438,2021,A1 .Location in patent: Page/Page column 20.

3
[ 689291-89-2 ]
[ 88284-48-4 ]
[ 3096-56-8 ]

References: [1]Journal of Organic Chemistry,2008,vol. 73,p. 6679 - 6685.

4
[ 689291-89-2 ]
[ 4546-04-7 ]
[ 1038395-08-2 ]

References: [1]Journal of Polymer Science, Part A: Polymer Chemistry,2015,vol. 53,p. 85 - 92.
[2]Organic Letters,2008,vol. 10,p. 3001 - 3004.

5
[ 689291-89-2 ]
[ 89343-06-6 ]
[ 1038395-11-7 ]

Yield	Reaction Conditions	Operation in experiment
94%	With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; at 20℃; for 24.0833h;Inert atmosphere;	Compound 12 (1.62 g, 5.20 mmol), triisopropylsilylacetylene (1.15 mL, 0.950 g, 5.20 mmol), PdCl2(PPh3)2 (46 mg, 0.065 mmol), and CuI (25 mg, 0.13 mmol) were added to Et3N (20 mL). The solution was bubbled with N2 at rt for 5 min and then stirred at rt and under N2 protection for 24 h. After the reaction was completed as checked by TLC analysis, the solvent was removed by rotary evaporation. The resulting residue was diluted with CHCl3. The mixture was filtered through a MgSO4 pad. The solution obtained was sequentially washed with HCl (aq 10%) and brine. The organic layer was dried over MgSO4 and concentrated under vacuum to give crude 23, which was further purified by silica flash column chromatography (hexanes/CH2Cl2, 4:1) to yield compound 23 (1.78 g, 4.87 mmol, 94%) as a colorless oil. IR (KBr) 2944, 2891, 2866, 2736, 2156, 1695, 1582, 1469, 1383 cm-1; 1H NMR (CDCl3, 500 MHz) δ 10.53 (s, 1H), 8.05 (d, J=2.0 Hz, 1H), 7.67 (dd, J=8.5, 1.5 Hz, 1H), 7.47 (d, J=8.0 Hz, 1H), 1.15 (s, 21H); 13C NMR (CDCl3, 125 MHz) δ 190.4, 137.5, 136.7, 135.4, 130.1, 125.9, 123.4, 101.1, 100.9, 18.8, 11.4; HRMS (CI) m/z calcd for C18H25BrOSi 364.0858, found 365.1071 [M+H]+.

References: [1]Organic Letters,2008,vol. 10,p. 3001 - 3004.
[2]Tetrahedron,2011,vol. 67,p. 125 - 143.

6
[ 75-77-4 ]
[ 689291-89-2 ]
[ 75-36-5 ]
1-(2-iodo-5-bromo-phenyl)-3-trimethylsilyloxy-2-aza-1,3-butadiene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 112b Preparation of intermediate 1-(2-iodo-5-bromo-phenyl)-3-trimethylsilyoxy-2-aza-1,3-butadiene To dry tetrahydrofuran (120 mL) was added a solution of LiHMDS (42 mmol, 42 ml) in THF under argon at room temperature, followed by the addition of 5-bromo-2-iodo-benzaldehyde (13 g, 42 mmol). After the mixture was stirred at room temperature for 0.5 h, trimethylsilyl chloride (5.32 mL, 42 mmol) was added dropwise. Then the temperature of the mixture was lowered to 0 C. on a cooling ice bath. To this mixture was added triethylamine (7.6 mL, 54.4 mmol) in one portion, followed by the dropwise addition of a solution of acetyl chloride (3.9 mL, 54.4 mmol) in diethyl ether (200 mL). The cooling bath was removed, and the mixture was stirred at room temperature for 1 h. The mixture was quickly filtered on celite under nitrogen, and filtrate was concentrated under reduced pressure to give the title compound as a yellow gum and used for the next step without further purification.

References: [1]Patent: US2009/156610,2009,A1 .Location in patent: Page/Page column 90.

7
[ 121554-10-7 ]
[ 689291-89-2 ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 112a Preparation of intermediate 5-bromo-2-iodo-benzaldehyde To a solution of 5-bromo-2-iodo-benzomitrile (1.54 g, 5 mmol) in DCM (15 mL) was added a solution of DIBALH (6 mL, 6 mmol) dropwise at 0 C. After the addition, the reaction mixture was warmed to r.t. and stirred for 2 h. Then the mixture was poured into 20 g of ice and 20 mL of 1N HCl, filtered and extracted by DCM (40 mL), washed with aqueous sodium bicarbonate, dried over MgSO4 and concentrated to give crude product (Yield: 1.2 g).
		Step 1: 5-Bromo-2-iodo-benzaldehyde To <strong>[121554-10-7]5-bromo-2-iodobenzonitrile</strong> (7.4 g, 24.2 mmol) in THF (40 mL) at -78 C. was added diisobutylaluminium hydride (1M in hexanes; 24.2 mL, 24.2 mmol) over 5 minutes, and the reaction was allowed to warm to room temperature and monitored by analytical tlc. After stirring overnight at room temperature, starting material was still present, so the mixture was cooled to 0 C. and additional diisobutylaluminium hydride (1M in hexanes; 10.0 mL, 10.0 mmol) was added. After stirring for 2 hours at room temperature, no starting material was seen by analytical tlc, so the mixture was carefully quenched with freshly saturated aqueous Na2SO4 and diluted with EtOAc. The mixture was stirred vigorously for 1 hour and then filtered through Celite. The filtrate was concentrated, and the resulting oil solidified on standing. The solid was stirred vigorously in CH2Cl2 and 1N aqueous HCl, and the aqueous layer was separated and extracted with CH2Cl2. The combined organic layers were dried over MgSO4, filtered, and concentrated to give the title compound.
		T o a s o l u t i o n o f <strong>[121554-10-7]5-bromo-2-iodobenzonitrile</strong> (5.0Og, 16 00mmoles) in anhydrous tetrahydrofuran (80ml) at -8O0C is added diisobutyl aluminium hydride (16.0ml, 16.0mmoles, 1 M solution in toluene) dropwise over 10 minutes. The reaction mixture is stirred at -8O0C for a 1 hour, then allowed to warm to ambient temperature and stir overnight. Additional diisobutyl aluminium hydride (16.0ml, 16.0mmoles, 1 M solution in toluene) is next added dropwise at room temperature, and the reaction mixture further stirred for 1hour. After careful quenching with 2M hydrochloric acid (cooling in ice bath), the crude product is extracted with ethyl acetate (x 2), then all organics are combined and dried over magnesium sulfate and filtered. The filtrate is evaporated under reduced pressure then purified by flash column chromatography (isohexane to 10% ethyl acetate in isohexane eluant) to afford 5-bromo-2- iodobenzaldehyde (0.85g).

References: [1]Patent: US2009/156610,2009,A1 .Location in patent: Page/Page column 90.
[2]Patent: US2009/197959,2009,A1 .Location in patent: Page/Page column 16.
[3]Patent: WO2010/136431,2010,A1 .Location in patent: Page/Page column 21-22.

8
[ 689291-89-2 ]
[ 75-04-7 ]
[ 1175525-90-2 ]

Yield	Reaction Conditions	Operation in experiment
		Step 2: (5-Bromo-2-iodo-benzyl)-ethyl-amine To 5-bromo-2-iodo-benzaldehyde (5.0 g, 16.1 mmol) in MeOH (20 mL) was added ethylamine (2M in MeOH; 16 mL, 24.0 mmol), followed by acetic acid (1.0 mL, 17.8 mmol), and the mixture was stirred at room temperature for 30 minutes. Sodium cyanoborohydride (2.0 g, 31.8 mmol) was then added over 5 minutes, and the reaction was stirred at room temperature over the weekend. The mixture was concentrated and partitioned between EtOAc and saturated aqueous NaHCO3. The aqueous layer was extracted with EtOAc, and the combined organic layers were dried over MgSO4, filtered, and concentrated. The residue was purified by silica gel chromatography (0-5% MeOH in CH2Cl2) to give the title compound.

References: [1]Patent: US2009/197959,2009,A1 .Location in patent: Page/Page column 16.

9
[ 689291-89-2 ]
[ 64-17-5 ]
[ 1222168-93-5 ]

Yield	Reaction Conditions	Operation in experiment
	With toluene-4-sulfonic acid; for 18h;Reflux;	Step 1: A mixture of <strong>[689291-89-2]5-bromo-2-iodobenzaldehyde</strong> (14.9) (1.0 g, 3.2 mmol) and PTSA (0.1 g) in ethanol was stirred under reflux for 18 hrs and concentrated under reduced pressure. The residue was dissolved in ethyl acetate and washed with saturated NaHCC>3, dried over anhydrous Na2SC^ and concentrated to give 4-bromo-2-(diethoxymethyl)-l-iodobenzene (14.10) that was directly used in next reaction without further purification.

References: [1]Patent: WO2010/48332,2010,A2 .Location in patent: Page/Page column 224; 231.

10
[ 4414-88-4 ]
[ 689291-89-2 ]
[ 1219685-39-8 ]

References: [1]Organic Letters,2010,vol. 12,p. 1500 - 1503.

11
[ 689291-89-2 ]
[ 5455-94-7 ]
[ 1257065-29-4 ]