[ CAS No. 133720-60-2 ] {[proInfo.proName]}

Name: 133720-60-2|7-Bromobenzofuran|98%
Brand: Ambeed
SKU: A118545
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Quality Control of [ 133720-60-2 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 133720-60-2 ]

Product Details of [ 133720-60-2 ]

CAS No. :	133720-60-2	MDL No. :	MFCD09056756
Formula :	C₈H₅BrO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	GPZPQJITKRSVQJ-UHFFFAOYSA-N
M.W :	197.03	Pubchem ID :	113628
Synonyms :

Calculated chemistry of [ 133720-60-2 ]

Physicochemical Properties

Num. heavy atoms :	10
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 :	43.91
TPSA :	13.14 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) :	-5.36 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.23
Log Po/w (XLOGP3) :	3.02
Log Po/w (WLOGP) :	3.2
Log Po/w (MLOGP) :	2.31
Log Po/w (SILICOS-IT) :	3.12
Consensus Log Po/w :	2.77

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	2.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-3.63
Solubility :	0.0462 mg/ml ; 0.000234 mol/l
Class :	Soluble
Log S (Ali) :	-2.96
Solubility :	0.216 mg/ml ; 0.00109 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-4.14
Solubility :	0.0142 mg/ml ; 0.0000719 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.36

Safety of [ 133720-60-2 ]

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 [ 133720-60-2 ]

* 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.

Upstream synthesis route of [ 133720-60-2 ]
Downstream synthetic route of [ 133720-60-2 ]

[ 133720-60-2 ] Synthesis Path-Upstream 1~8

1
[ 204452-94-8 ]
[ 128851-73-0 ]
[ 133720-60-2 ]

Reference： [1] Patent: US2010/280013, 2010, A1, . Location in patent: Page/Page column 42
[2] Patent: WO2015/66371, 2015, A1, . Location in patent: Paragraph 00384-00385

2
[ 591-20-8 ]
[ 128851-73-0 ]
[ 133720-60-2 ]

Reference： [1] Patent: WO2015/66371, 2015, A1,

3
[ 253429-15-1 ]
[ 133720-60-2 ]

Yield	Reaction Conditions	Operation in experiment
73%	Stage #1: With PPA In chlorobenzene for 2.15 h; Heating / reflux Stage #2: With sodium hydroxide In water; chlorobenzene at 20℃;	Scheme I, step B: Polyphosphoric acid (60 g) and chlorobenzene (100 mL) were combined and heated to reflux. To the refluxing mixture was added dropwise 2-(2-bromophenol) acetaldehyde diethyl acetal (27 g, 0.093 mol, prepared above in Scheme I, step A) dissolved in chlorobenzene (20 mL), over 15 minutes. Heating of the reaction mixture at reflux was continued for 2 hours and then it was cooled to room temperature. 1N sodium hydroxide (100 mL), was added and the reaction was stirred at room temperature overnight. The reaction mixture was then extracted with diethyl ether (3.x.100 mL), the organic extracts were combined, dried over anhydrous sodium sulfate, filtered and concentrated under vacuum. The residue was purified by flash chromatography (hexane, silica gel) to provide the 7-bromobenzo(b)furan (13.4 g, 73percent) as a clear oil.
58%	With polyphosphoric acid In 1,2-dichloro-ethane at 83℃; for 3 h; Inert atmosphere	1-Bromo-2-(2,2-diethoxyethoxy)benzene (0102-3)(3.33g, 11.56mol, 1.0 equivalent)Soluble in DCE (60ml), add PPA(11.72g, 34.68mmol, 3.0 equivalents),The air in the round bottom flask was replaced with nitrogen three times and then refluxed at 83 ° C for 3 hours.After the reaction was completed, dichloromethane (100 ml) was added, and water (100 ml × 3) was washed.The organic phase was dried over anhydrous sodium sulfate and concentrated.Then purified by silica gel column chromatography (petroleum ether = 100percent) to give pale-yellow solid product 7-bromobenzofuran(1.336 g, yield: 58percent).
38%	Stage #1: With PPA In chlorobenzene for 1.66667 h; Heating / reflux Stage #2: With sodium hydroxide In water; chlorobenzene at 20℃;	A stirred mixture of polyphosphoric acid (~5 g) and chlorobenzene (8 mL) was heated at reflux and a solution of l-(2,2-diethoxyelhoxy)-2-bromobenzene (2.62 g, 9.0 mmol) in chlorobenzene (3 mL) was added dropwise over 10 min. The mixture was heated at reflux for 1.5 h. The mixture was allowed to cool to rt and IM aq NaOH (20 mL) was added, followed by ether (175 mL). The mixture was washed with water (2 x 20 mL) and brine (20 mL), and dried over MgSO₄. Evaporation of the solvent left a residue which was purified by a chromatography on a 140-g silica <n="142"/>cartridge eluted with hexanes and a 0-10percent EtOAc in hexanes gradient. Appropriate fractions were pooled and concentrated to afford 7-bromobenzofuran (0.65 g, 38percent from 2-bromophenol) as a clear colorless oil.

Reference： [1] Patent: US6353008, 2002, B1, . Location in patent: Page column 38
[2] Patent: CN108658908, 2018, A, . Location in patent: Paragraph 0160; 0162
[3] Patent: WO2007/117560, 2007, A2, . Location in patent: Page/Page column 140-141
[4] Heterocyclic Communications, 2010, vol. 16, # 4-6, p. 249 - 252
[5] Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 7, p. 2007 - 2017
[6] Patent: WO2015/95261, 2015, A1, . Location in patent: Page/Page column 36; 37
[7] Patent: WO2015/89842, 2015, A1, . Location in patent: Page/Page column 36-37
[8] New Journal of Chemistry, 2016, vol. 40, # 8, p. 6564 - 6567

4
[ 253429-15-1 ]
[ 133720-60-2 ]

Yield	Reaction Conditions	Operation in experiment
73%	With sodium hydroxide; PPA In chlorobenzene	Preparation of 7-Bromobenzo(b)furan Scheme 1, step B: Polyphosphoric acid (60 g) and chlorobenzene (100 mL) were combined and heated to reflux. To the refluxing mixture was added dropwise 2-(2-bromophenol) acetaldehyde diethyl acetal (27 g, 0.093 mol, prepared above in Scheme I, step A) dissolved in chlorobenzene (20 mL) over 15 minutes. Heating of the reaction mixture at reflux was continued for 2 hours and then it was cooled to room temperature. 1N sodium hydroxide (100 mL) was added and the reaction was stirred at room temperature overnight. The reaction mixture was then extracted with diethyl ether (3*100 mL), the organic extracts were combined, dried over anhydrous sodium sulfate, filtered and concentrated under vacuum. The residue was purified by flash chromatography (hexane, silica gel) to provide the 7-bromobenzo(b)furan (13.4 g, 73percent) as a clear oil.

Reference： [1] Patent: US6465453, 2002, B1,

5
[ 204452-94-8 ]
[ 128851-73-0 ]
[ 133720-60-2 ]

Reference： [1] Patent: US2010/280013, 2010, A1, . Location in patent: Page/Page column 42
[2] Patent: WO2015/66371, 2015, A1, . Location in patent: Paragraph 00384-00385

6
[ 95-56-7 ]
[ 133720-60-2 ]

Reference： [1] Heterocyclic Communications, 2010, vol. 16, # 4-6, p. 249 - 252
[2] Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 7, p. 2007 - 2017
[3] Patent: WO2015/95261, 2015, A1,
[4] Patent: WO2015/89842, 2015, A1,
[5] New Journal of Chemistry, 2016, vol. 40, # 8, p. 6564 - 6567
[6] Patent: CN103724305, 2016, B,
[7] Patent: WO2007/117560, 2007, A2,
[8] Patent: CN108658908, 2018, A,

7
[ 95-56-7 ]
[ 128868-60-0 ]
[ 133720-60-2 ]

Reference： [1] Patent: EP1204654, 2003, B1,
[2] Patent: EP1204654, , A1, [2] Patent: , 2002, ,

8
[ 591-20-8 ]
[ 128851-73-0 ]
[ 133720-60-2 ]

Reference： [1] Patent: WO2015/66371, 2015, A1,

[ 133720-60-2 ] Synthesis Path-Downstream 1~88

1
[ 75-77-4 ]
[ 133720-60-2 ]
[ 884512-42-9 ]

Yield	Reaction Conditions	Operation in experiment
		A stirred solution of diisopropylamine (0.65 mL, 4.7 mmol) in THF (15 L) was cooled to 5C and n-BuLi (2.5 M in hexanes, 1.9 mL, 4.7 mmol) was added dropwise over 5 min. The mixture was stirred at 5C for 15 min and cooled to - 700C. Chlorotrimethylsilane (0.59 mL, 4.7 mmol) was added followed by a solution of <strong>[133720-60-2]7-bromobenzofuran</strong> (0.46 g, 2.35 mmoi) in THF (5 mL). The mixture was stirred at -700C for 1.5 h and poured into sat'd aq NH4Cl (80 mL). The mixture was diluted with 5% aq HCI (20 mL) and extracted with ether (2 x 80 mL). The combined ether extracts were washed with sat'd aq NaHCO3 (50 mL), dried over MgSO4 and concentrated to leave crude 7-bromo-2-(trimethylsilyl)benzofuran (0.62 g, 98%) as a yellow oil.

Reference： [1]Patent: WO2007/117560,2007,A2 .Location in patent: Page/Page column 141

2
7-bromo-2,3-dihydrobenzofuran-2-ol [ No CAS ]
[ 133720-60-2 ]

Yield	Reaction Conditions	Operation in experiment
	With phosphoric acid; phosphorus pentoxide; In chlorobenzene; at 20 - 95℃; for 15h;	A suspension of potassium carbonate (50.0g, 362mmol) in 100ml of DMF was added sequentially with 2-bromophenol (20.6g, 120mmol) and bromoacetaldehyde dimethyl acetal (20.2g, 120mmol) and stirred at 95C for 15 hours. The reaction solution was concentrated, liquid separation was carried out with ethyl acetate-water, the organic layer was sequentially washed with an aqueous solution of 1M-sodium hydroxide and saturated sodium chloride water, and dried with anhydrous magnesium sulfate. The residue obtained by concentration was dissolved in 200ml of chlorobenzene, added at room temperature to a solution comprising diphosphorus pentoxide (8.07g, 56.8mmol) and 85% phosphoric acid (27ml), which was stirred at 95C for 15 hours. After cooling to room temperature, the mixture was poured over ice water, stirred, and then extracted with dichloromethane. The organic layer was washed with saturated sodium chloride water and dried with anhydrous magnesium sulfate. The residue obtained by concentration was purified by silica gel chromatography (100% hexane) to obtain an oily product (10.4g, 47%). 1H-NMR (300MHz, CDCl3) delta=6.84 (1H, d, J=2.4Hz), 7.12 (1H, t, J=7.8Hz), 7.46 (1H, dd, J=2.4, 7.8Hz), 7.54 (1H, dd, J=2.4, 7.8Hz), 7.69 (1H, d, J=2.4Hz).

Reference： [1]Patent: EP1878734,2008,A1 .Location in patent: Page/Page column 13

3
[ 133720-60-2 ]
benzofuran-7-sulfonic acid amide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 617 - 620

4
[ 133720-60-2 ]
benzofuran-7-sulfonic acid 2,4-dichloro-benzoylamide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 617 - 620

5
[ 133720-60-2 ]
4-benzofuran-7-yl-1-(5-fluoro-1-oxo-indan-2-yl)-pyridinium; bromide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 165 - 176

6
[ 133720-60-2 ]
[ 98224-26-1 ]

Reference： [1]Tetrahedron Letters,1998,vol. 39,p. 2219 - 2222

7
[ 253429-15-1 ]
[ 133720-60-2 ]

Yield	Reaction Conditions	Operation in experiment
73%		Scheme I, step B: Polyphosphoric acid (60 g) and chlorobenzene (100 mL) were combined and heated to reflux. To the refluxing mixture was added dropwise 2-(2-bromophenol) acetaldehyde diethyl acetal (27 g, 0.093 mol, prepared above in Scheme I, step A) dissolved in chlorobenzene (20 mL), over 15 minutes. Heating of the reaction mixture at reflux was continued for 2 hours and then it was cooled to room temperature. 1N sodium hydroxide (100 mL), was added and the reaction was stirred at room temperature overnight. The reaction mixture was then extracted with diethyl ether (3×100 mL), the organic extracts were combined, dried over anhydrous sodium sulfate, filtered and concentrated under vacuum. The residue was purified by flash chromatography (hexane, silica gel) to provide the 7-bromobenzo(b)furan (13.4 g, 73%) as a clear oil.
58%	With polyphosphoric acid; In 1,2-dichloro-ethane; at 83℃; for 3h;Inert atmosphere;	1-Bromo-2-(2,2-diethoxyethoxy)benzene (0102-3)(3.33g, 11.56mol, 1.0 equivalent)Soluble in DCE (60ml), add PPA(11.72g, 34.68mmol, 3.0 equivalents),The air in the round bottom flask was replaced with nitrogen three times and then refluxed at 83 C for 3 hours.After the reaction was completed, dichloromethane (100 ml) was added, and water (100 ml × 3) was washed.The organic phase was dried over anhydrous sodium sulfate and concentrated.Then purified by silica gel column chromatography (petroleum ether = 100%) to give pale-yellow solid product 7-bromobenzofuran(1.336 g, yield: 58%).
38%		A stirred mixture of polyphosphoric acid (~5 g) and chlorobenzene (8 mL) was heated at reflux and a solution of l-(2,2-diethoxyelhoxy)-2-bromobenzene (2.62 g, 9.0 mmol) in chlorobenzene (3 mL) was added dropwise over 10 min. The mixture was heated at reflux for 1.5 h. The mixture was allowed to cool to rt and IM aq NaOH (20 mL) was added, followed by ether (175 mL). The mixture was washed with water (2 x 20 mL) and brine (20 mL), and dried over MgSO4. Evaporation of the solvent left a residue which was purified by a chromatography on a 140-g silica <n="142"/>cartridge eluted with hexanes and a 0-10% EtOAc in hexanes gradient. Appropriate fractions were pooled and concentrated to afford 7-bromobenzofuran (0.65 g, 38% from 2-bromophenol) as a clear colorless oil.

	With phosphoric acid; In chlorobenzene; for 2.5h;Reflux;	Step 2: Polyphosphoric acid (480 g) and chlorobenzene (800 mL) were combined and themixture was heated to reflux. To the refluxing mixture was added dropwise a solution of Si-i(224 g, 0.744 mol) in chlorobenzene (160 mL) over 30 mins. The reaction mixture was refluxed for 2 hrs, then it was cooled to room temperature. iN NaOH (800 mL) was added and the mixture was stirred at room temperature overnight. The reaction mixture was extracted with ethyl acetate. The organic layer was washed with brine, separated, dried over anhydrous sodium sulfate, filtered, and concentrated to afford the product which was purified by silica gel to giveS1-2.
	With polyphosphoric acid; In chlorobenzene; for 2.5h;Reflux;	Step 2: Polyphosphoric acid (480 g) and chlorobenzene (800 mL) were combined and the mixture was heated to reflux. To the refluxing mixture was added dropwise a solution of Sl-1 (224 g, 0.744 mol) in chlorobenzene (160 mL) over 30 mins. The reaction mixture was refluxed for 2 hrs, then it was cooled to room temperature. IN NaOH (800 mL) was added and the mixture was stirred at room temperature overnight. The reaction mixture was extracted with ethyl acetate. The organic layer was washed with brine, separated, dried over anhydrous sodium sulfate, filtered, and concentrated to afford the product which was purified by silica gel to give Sl-2.

Reference： [1]Patent: US6353008,2002,B1 .Location in patent: Page column 38
[2]Patent: CN108658908,2018,A .Location in patent: Paragraph 0160; 0162
[3]Patent: WO2007/117560,2007,A2 .Location in patent: Page/Page column 140-141
[4]Heterocyclic Communications,2010,vol. 16,p. 249 - 252
[5]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 2007 - 2017
[6]Patent: WO2015/95261,2015,A1 .Location in patent: Page/Page column 36; 37
[7]Patent: WO2015/89842,2015,A1 .Location in patent: Page/Page column 36-37
[8]New Journal of Chemistry,2016,vol. 40,p. 6564 - 6567
[9]Angewandte Chemie - International Edition,2019,vol. 58,p. 10148 - 10152
Angew. Chem.,2019,vol. 131,p. 10254 - 10258,5

Yield	Reaction Conditions	Operation in experiment
73%		Preparation of 7-Bromobenzo(b)furan. Scheme I, step B: Polyphosphoric acid (60 g) and chlorobenzene (100 mL) were combined and heated to reflux. To the refluxing mixture was added dropwise 2-(2-bromophenol)acetaldehyde diethyl acetal (27 g, 0.093 mol, prepared above in Scheme I, step A) dissolved in chlorobenzene (20 mL) over 15 minutes. Heating of the reaction mixture at reflux was continued for 2 hours and then it was cooled to room temperature. 1N sodium hydroxide (100 mL) was added and the reaction was stirred at room temperature overnight. The reaction mixture was then extracted with diethyl ether (3*100 mL), the organic extracts were combined, dried over anhydrous sodium sulfate, filtered and concentrated under vacuum. The residue was purified by flash chromatography (hexane, silica gel) to provide the 7-bromobenzo(b)furan (13.4 g, 73%) as a clear oil.

9
[ 34737-89-8 ]
[ 133720-60-2 ]
cis-3-methyl-4-(benzofuran-7-yl)piperidine hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
21%		EXAMPLE 43 cis -3-methyl-4-(benzofur-7-yl)piperidine hydrochloride Beginning with 7 gm (35.5 mMol) <strong>[133720-60-2]7-bromobenzofuran</strong> and 7.9 gm (39 mMol) 1-benzyl-3-methyl-4-oxopiperidine, 1.92 gm (21%) of the title compound were prepared as a white powder essentially as described in EXAMPLE 19. EA: Calculated for C14H17NO-HCl: C, 66.79; H, 7.21; N, 5.56. Found: C, 66.41; H, 7.02; N, 5.70.

Reference： [1]Patent: EP1204659,2003,B1 .Location in patent: Page/Page column 49

10
[ 253429-15-1 ]
4-(7-Benzo(b)furan-1-aza-3-cycloheptenyl)-1-cyclohexyl-2-(2-pyridyl)butan-1-one [ No CAS ]
[ 133720-60-2 ]

Yield	Reaction Conditions	Operation in experiment
73%	With sodium hydroxide; PPA; In chlorobenzene;	Preparation of 7-Bromobenzo(b)furan Scheme 1, step B: Polyphosphoric acid (60 g) and chlorobenzene (100 mL) were combined and heated to reflux. To the refluxing mixture was added dropwise 2-(2-bromophenol) acetaldehyde diethyl acetal (27 g, 0.093 mol, prepared above in Scheme I, step A) dissolved in chlorobenzene (20 mL) over 15 minutes. Heating of the reaction mixture at reflux was continued for 2 hours and then it was cooled to room temperature. 1N sodium hydroxide (100 mL) was added and the reaction was stirred at room temperature overnight. The reaction mixture was then extracted with diethyl ether (3*100 mL), the organic extracts were combined, dried over anhydrous sodium sulfate, filtered and concentrated under vacuum. The residue was purified by flash chromatography (hexane, silica gel) to provide the 7-bromobenzo(b)furan (13.4 g, 73%) as a clear oil.

Reference： [1]Patent: US6465453,2002,B1

11
[ 133720-60-2 ]
[ 111538-45-5 ]
Trans-2-[4-(benzofuran-7-yl)piperid-1-yl]-5-fluoroindan-1-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 24 Trans-2-[4-(benzofuran-7-yl)piperid-1-yl]-5-fluoroindan-1-ol Prepared using, in succession, the methods described in Examples 18, 19 and 23, but using <strong>[133720-60-2]7-bromobenzofuran</strong> instead of 5-bromo-2,3-dihydro[1,4]benzodioxine in Step 1 of Example 18, and using 2-bromo-5-fluoroindan-1-one instead of 2-bromo-indan-1-one in Step 2 of Example 18. The melting point (MK) of the title compound is 170-172 C.

Reference： [1]Patent: US5958927,1999,A

12
bis-(dibenzylideneacetone)palladium (O) [ No CAS ]
[ 6163-58-2 ]
[ 133720-60-2 ]
[ 57260-71-6 ]
[ 187795-32-0 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium t-butanolate; In toluene; Petroleum ether;	Tri-o-tolylphosphine (1.42 g) was added to a stirred suspension of bis (dibenzylideneacetone) palladium (O) (1.4 g) in toluene (480 ml) at ambient temperature under nitrogen. Sodium tert-butoxide (16.1 g) was added, followed by N-tert-butoxycarbonylpiperazine (26.6 g) and stirring was continued at ambient temperature for 5 minutes. <strong>[133720-60-2]7-Bromobenzo[b]furan</strong> (23.3 g) was added and the stirred mixture was heated under reflux for 20 hours and then cooled to ambient temperature. The organic solution was decanted from the palladium residues, then washed with brine (500 ml) and dried (MgSO4). The solvent was removed in vacuo and the residue was purified by flash column chromatography over silica using a 1:9 mixture of ether and petroleum ether (b.p. 60-80 C.) as eluant to give tert-butyl 4-(7-benzo[b]furanyl)piperazine-1-carboxylate (7.12 g) as a pale yellow solid, m.p. 98-100 C.

Reference： [1]Patent: US6114334,2000,A

13
1-bromo-2-(2,2-dimethoxyethoxy)benzene [ No CAS ]
[ 133720-60-2 ]

Yield	Reaction Conditions	Operation in experiment
	With phosphorus pentaoxide; phosphoric acid; In water; chlorobenzene; Petroleum ether;	A mixture of phosphorus pentoxide (19.3 g) and phosphoric acid (64 ml, 85%) was added carefully to a stirred solution of 2-(2-bromophenoxy)acetaldehyde dimethyl acetal (69.6 g) in chlorobenzene (450 ml) at ambient temperature under nitrogen. The mixture was then heated under reflux for 20 hours, cooled and poured into ice/water (500 ml). The aqueous layer was separated and washed with dichloromethane (2*250 ml). The combined organic extracts were washed with brine (400 ml), dried (MgSO4), and the solvent removed in vacuo. The residue was purified by flash column chromatography over silica using a 1:49 mixture of ether and petroleum ether (b.p. 60-80 C.) as the eluant, followed by distillation to give 7-bromobenzo[b]furan (30.3 g) as a clear oil, b.p. 66-68 C. at 0.93 mbar.
169 g	In chlorobenzene; for 27h;Reflux;	Chlorobenzene (1000 mL) was added to a 5000 mL three-necked bottomed flask, followed by the addition of the crude 1-bromo-4 '- (2,2-dimethoxyethyl) benzene (310 g) 810 g).The stirring was started and heated under reflux for 27 hours.TLC and GC tracking reactions.After completion of the reaction, the reaction solution was cooled to room temperature and the lower layer was separated.The organic phase was washed with water (550 mL) and sodium hydroxide (2 mol / L, 550 mL).Dried over sodium sulfate overnight.After filtration, most of the chlorobenzene was distilled off.And then distilled under reduced pressure to give the crude product 7-bromobenzofuran (265 g).After distillation, pure 7-bromobenzofuran 169 g, yield 70.7%.

Reference： [1]Patent: US6114334,2000,A
[2]Patent: CN103724305,2016,B .Location in patent: Paragraph 0022; 0024

14
[ 95-56-7 ]
[ 128868-60-0 ]
[ 133720-60-2 ]

Yield	Reaction Conditions	Operation in experiment
		Preparation VI 7-bromobenzofuran Beginning with 10 gm (57.8 mMol) 2-bromophenol, 5 gm (45%) of the title compound were prepared essentially by the procedure described in Preparation IV. EA: Calculated for C8H5BrO: Theory: C, 48.77; H, 2.56. Found: C, 49.02; H, 2.82.

Reference： [1]Patent: EP1204654,A1
Patent: ,2002,

15
[ 101385-93-7 ]
[ 133720-60-2 ]
1-(t-butoxycarbonyl)-3-(7-benzo(b)furan)-3-hydroxypyrrolidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Scheme I, step C: A 500 mL round bottom flask is charged with anhydrous THF (150 mL), and <strong>[133720-60-2]7-bromobenzo(b)furan</strong> (13.0 g, 0.066 mol, prepared above in Scheme I, step B), and the solution is cooled to -78 C. n-Butyllithium (41.2 mL of a 1.6 M solution in THF, 0.066 mol) is added over 3 minutes followed by addition of 1-(t-butoxycarbonyl)-3-pyrrolidone (0.063 mol). The reaction mixture is then allowed to warm to room temperature over 18 hours with stirring. The reaction is then quenched with water (4 mL) and extracted with ethyl acetate. The organic extracts are combined, dried over anhydrous sodium sulfate, filtered and concentrated under vacuum to provide a tan oil. The tan oil is then purified by flash chromatography (silica gel, 2 times) to provide the title compound

Reference： [1]Patent: US6353008,2002,B1 .Location in patent: Page column 39

16
[ 1169760-26-2 ]
[ 133720-60-2 ]
[ 1169760-25-1 ]

Reference： [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 4149 - 4160

17
[ 68-12-2 ]
[ 133720-60-2 ]
[ 95333-14-5 ]

Yield	Reaction Conditions	Operation in experiment
85%		Magnesium powder (1.33g, 54.7mmol) was dried by reduced pressure while heating, cooled to room temperature, then THF was added so as to soak the magnesium. An amount of 10mg of iodide was added, 0.45g of Step 1 compound was gradually added, at the point when heating started, a solution of 10.0g of Step 1 compound in 106ml of THF was added drop-wise gradually (total Step 1 compound: 10.45g, 53.0mmol). The reaction solution in reflux state was heated further to 85C and stirred for 1.5 hours. The reaction solution was cooled to 0C, was added with DMF (6.15ml, 73.9mmol), and stirred at room temperature for 30 minutes. The reaction was stopped by adding 50ml of a saturated aqueous solution of ammonium chloride, the organic solvent was evaporated, and then liquid separation was carried out with ethyl acetate-water. The aqueous layer was extracted three times with ethyl acetate, and the pooled organic layer was washed with saturated sodium chloride water and dried with anhydrous magnesium sulfate. The residue obtained by concentration was purified by silica gel chromatography (hexane:ethyl acetate=80:20) to obtain the title compound (6.62g, 85%). 1H-NMR (300MHz, CDCl3) delta=6.87 (1H, d, J=2.4Hz), 7.39 (1H, t, J=7.8Hz), 7.78 (1H, d, J=2.4Hz), 7.80 (1H, dd, J=2.4, 7.8Hz), 7.88 (1H, dd, J=2.4, 7.8Hz), 10.45 (1H, s).

Reference： [1]Patent: EP1878734,2008,A1 .Location in patent: Page/Page column 13

18
[ 204452-94-8 ]
[ 128851-73-0 ]
[ 133720-60-2 ]

Yield	Reaction Conditions	Operation in experiment
	With (1R,2S)-norephedrine; In toluene;Reflux;	b) Preparation of 6-bromobenzofuran To a solution of 1-bromo-3-(2,2-diethoxyethoxy)benzene (2.3 g, 8.35 mmol) in toluene (28 mL), was added PPA (5.0 mL) and refluxed for overnight. The reaction solution was added water at room temperature, and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, concentrated in vacuo, and purified by silica-gel column chromatography (hexane). The title compound (1.2 g (yield 68%, mixture with 7-bromobenzofuran)) was obtained as a yellow oil. 1H-NMR (CDCl3) delta: 6.75 (1H, d, J=2.4 Hz), 7:36 (1H, d, J=8.1 Hz), 7.46 (1H, d, J=8.1 Hz), 7.60 (1H, d, J=2.4 Hz), 7.68 (1H, s).
	With polyphosphoric acid; In toluene; for 3h;Reflux;	To a solution of compound B-191 (50 g, 0.18 mol) in toluene (500 mL) was added polyphosphoric acid (20 g) at room temperature. The mixture was heated to reflux for 3 hours. On completion, the reaction mixture was diluted with hot water (200 mL) and extracted with dichloromethane (3 x 500 mL). The combined organic layers were washed with brine (2 x 500 mL), dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified by silica gel column chromatography [petroleum ether: ethyl acetate = 20: 1 ] to give a mixture of compound B-192 and compound B-193 (1 1 g, 29% yield) as yellow oil

Reference： [1]Patent: US2010/280013,2010,A1 .Location in patent: Page/Page column 42
[2]Patent: WO2015/66371,2015,A1 .Location in patent: Paragraph 00384-00385

19
[ 97674-02-7 ]
[ 128851-73-0 ]
[ 133720-60-2 ]
6-acetylbenzo[b]furan [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	tetrakis(triphenylphosphine) palladium(0); In toluene; at 100℃;	c) Preparation of 1-(benzofuran-6-yl)ethanone To a solution of a mixture of 6-bromobenzofuran and <strong>[133720-60-2]7-bromobenzofuran</strong> (1.12 g, 5.68 mmol) in toluene (19 mL), tetrakistriphenyl phosphine palladium (650 mg, 0.57 mmol) and tributyl(1-ethoxyvinyl)tin (2.11 mL, 6.25 mmol) were added, and the mixture was stirred at 100 C. overnight. The reaction solution was added water at room temperature, and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, concentrated in vacuo, and purified by silica-gel column chromatography (hexane). The title compound (280 mg) was obtained as a yellow crystal. 1H-NMR (CDCl3) delta: 2.67 (3H, s), 6.83 (1H, d, J=1.9 Hz), 7.65 (1H, d, J=8.4 Hz), 7.78 (1H, d, J=1.9 Hz), 7.89 (1H, d, J=8.4 Hz), 8.12 (1H, s).

Reference： [1]Patent: US2010/280013,2010,A1 .Location in patent: Page/Page column 43

20
[ 109-01-3 ]
[ 133720-60-2 ]
7-(N-methylpiperazino)benzo[b]furan [ No CAS ]

Reference： [1]Heterocyclic Communications,2010,vol. 16,p. 249 - 252

21
[ 95-56-7 ]
[ 133720-60-2 ]

Reference： [1]Heterocyclic Communications,2010,vol. 16,p. 249 - 252
[2]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 2007 - 2017
[3]Patent: WO2015/95261,2015,A1
[4]Patent: WO2015/89842,2015,A1
[5]New Journal of Chemistry,2016,vol. 40,p. 6564 - 6567
[6]Patent: CN103724305,2016,B
[7]Patent: WO2007/117560,2007,A2
[8]Patent: CN108658908,2018,A
[9]Angewandte Chemie - International Edition,2019,vol. 58,p. 10148 - 10152
Angew. Chem.,2019,vol. 131,p. 10254 - 10258,5

22
[ 133720-60-2 ]
C₁₂H₈ClN₃O₃ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 2007 - 2017

23
[ 133720-60-2 ]
3-chlorobenzofuran-7-carbaldehyde [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 2007 - 2017

24
[ 133720-60-2 ]
C₁₈H₁₃ClN₂O₄ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 2007 - 2017

25
[ 133720-60-2 ]
[ 1368229-56-4 ]

Yield	Reaction Conditions	Operation in experiment
60%		A solution of <strong>[133720-60-2]7-bromobenzofuran</strong> 40 (20 g, 101 mmol) in acetic acid (150 mL) was cooled to 15 C and a gentle stream of chlorine was passed through the mixture for 0.5 h. The reaction mixture was concentrated in vacuo, diluted with water and extracted with ether (1 L). The ether layer was washed with water, dried (MgSO4), filtered and concentrated in vacuo. KOH (28 g) was dissolved in methanol (300 mL) and a solution of the crude dichlorinated compound was added dropwise into the base. The reaction mixture was stirred at room temperature for 20 min. The reaction mixture was concentrated in vacuo when a colorless solid precipitated out. The solid was filtered washed with water and dried to yield 41 (14 g, 60%) as a colorless solid. 1H NMR (400 MHz, CDCl3), delta, 7.72 (s, 1H), 7.55 (d, 1H, J = 7.6 and 1.2 Hz), 7.53 (d, 1H, J = 7.6 and 1.2 Hz), 7.21 (t, 1H, J = 7.6 Hz).

Reference： [1]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 2007 - 2017

26
[ 133720-60-2 ]
[ 1428415-53-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 2007 - 2017

27
[ 133720-60-2 ]
C₂₅H₁₇ClF₂N₂O₄ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 2007 - 2017

28
[ 133720-60-2 ]
[ 1428415-54-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 2007 - 2017

29
[ 133720-60-2 ]
methyl 4-hydroxyindole-2-carboxylate [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 2007 - 2017

30
[ 133720-60-2 ]
[ 1037758-48-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 2007 - 2017

31
1-[(triisopropylsilyl)ethynyl]-1,2-benziodoxol-3(1H)-one [ No CAS ]
[ 133720-60-2 ]
((7-bromobenzofuran-2-yl)ethynyl)triisopropylsilane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	With zinc trifluoromethanesulfonate; gold(I) chloride; In acetonitrile; at 60℃; for 26h;	TIPS-EBX (8, 342 mg, 0.800 mmol, 2.0 equiv), AuCl (4.6 mg,0.020 mmol, 0.050 equiv), Zn(OTf)2 (289 mg, 0.800 mmol, 2.0 equiv) and benzofuran derivatives 7 (0.40 mmol, 1.0 equiv) were added into CH3CN (2.0 mL) under air. The mixture was stirred for 26 hours at 60 C. Then the mixture was concentrated with silica gel and purified by column chromatography directly.

Reference： [1]Beilstein Journal of Organic Chemistry,2013,vol. 9,p. 1763 - 1767

32
[ 133720-60-2 ]
[ 98-80-6 ]
[ 35664-72-3 ]

Yield	Reaction Conditions	Operation in experiment
89%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 90℃;Inert atmosphere;	A schlenk tube was charged with boronic acid 15 (89 mg, 0.73 mmol, 1.0 equivPd(PPh3)4 (42 mg, 0.050 mmol, 0.05 equiv), Na2CO3 (77 mg, 0.73 mmol, 1.0 equiv), DME (1.0 mL) andH2O (2.5 mL). After degassing the mixture, <strong>[133720-60-2]7-bromobenzofuran</strong> (7f, 158 mg, 0.880 mmol, 1.1equiv) was added. The mixture was heated to 90 C and stirred overnight under N2. Then, the mixture was filtered through a plug of celite, and diluted with CH2Cl2 (10 mL). The organic layer was washed with 1 M NaOH (10 mL), brine (10 mL), dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by columnchromatography (SiO2; pentane) to afford 7g as a colorless oil (126 mg, 0.649 mmol, 89%). Rf (pentane): 0.3.1H NMR (400 MHz, CDCl3) delta 7.92 (m, 2 H, ArH), 7.72 (d, 1 H, J = 2.2 Hz, FuranH), 7.63(dd, 1 H, J = 7.7, 1.1 Hz, ArH), 7.55 (m, 2 H, ArH), 7.51 (dd, 1 H, J = 7.5, 1.1 Hz, ArH), 7.44(m, 1 H, ArH), 7.37 (m, 1 H, ArH), 6.87 (d, 1 H, J = 2.2 Hz, FuranH). 13C NMR (101 MHz,CDCl3) delta 152.2, 145.0, 136.5, 128.6, 128.5, 128.1, 127.6, 125.6, 123.8, 123.3, 120.4, 106.7.The NMR data corresponds to the literature.3

Reference： [1]Beilstein Journal of Organic Chemistry,2013,vol. 9,p. 1763 - 1767

33
[ 88284-48-4 ]
[ 133720-60-2 ]
1-bromo-8b,9-dihydro-9,13b-epoxybenzo[3,4]cyclobuta[1,2-k]phenanthrene [ No CAS ]

Reference： [1]Organic Letters,2014,vol. 16,p. 3576 - 3579

34
[ 292638-84-7 ]
[ 133720-60-2 ]
C₁₆H₁₁BrO [ No CAS ]

Reference： [1]ChemCatChem,2014,vol. 6,p. 1531 - 1534

35
[ 192182-56-2 ]
[ 133720-60-2 ]
[ 1610790-47-0 ]

Reference： [1]ACS Medicinal Chemistry Letters,2014,vol. 5,p. 760 - 765

36
[ 133720-60-2 ]
(1-benzofuran-7-yl)2phosphinechloride [ No CAS ]

Reference： [1]Patent: WO2014/181247,2014,A1

37
[ 133720-60-2 ]
(1-benzofuran-7-yl)2PN(n-hex)P(phenyl)2 [ No CAS ]

Reference： [1]Patent: WO2014/181247,2014,A1

38
[ 133720-60-2 ]
(1-benzofuran-7-yl)2PN(n-Hex)H [ No CAS ]

Reference： [1]Patent: WO2014/181247,2014,A1

39
[ 133720-60-2 ]
1-benzofuran-7-yl magnesium bromide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With iodine; magnesium; In tetrahydrofuran; for 0.25h;Reflux;	Preparation of 1-benzofuran-7-vi magnesium bromide To magnesium turnings (450 mg, 18.8 mmol) in THF (5 mL) was added 1 iodine crystal and a few drops of <strong>[133720-60-2]7-bromobenzofuran</strong>. A vigorous reaction ensued. The remaining <strong>[133720-60-2]7-bromo-benzofuran</strong> (3.6 g, 18.4 mmoi) in THF (10 ml) was added dropwise. The reaction mixture was left to reflux by itself. Once the reaction exotherm had dissipated, the reaction mixture was heated under reflux for about 15 minutes to yield the required Grignard reagent.
	With iodine; magnesium; In tetrahydrofuran; for 0.25h;Reflux;	Preparation of 1-benzofuran-7-yl magnesium bromide To magnesium turnings {225 mg, 9.4 mmol) in THF (5 mL) was added 1 iodine crystal and a few drops of <strong>[133720-60-2]7-bromobenzofuran</strong>. A vigorous reaction ensued. The remaining <strong>[133720-60-2]7-bromobenzofuran</strong> (1.8 g, 9.1 mmoi) in THF (10 mi) was added dropwise. The reaction mixture was left to reflux by itself. Once the reaction exotherm had dissipated, the reaction mixture was heated under reflux for about 15 minutes to yieid the required Grignard reagent.

Reference： [1]Patent: WO2014/181250,2014,A1 .Location in patent: Page/Page column 33
[2]Patent: WO2014/181247,2014,A1 .Location in patent: Page/Page column 27

40
[ 133720-60-2 ]
(1-benzofuran-7-yl)(phenyl)phosphine chloride [ No CAS ]

Reference： [1]Patent: WO2014/181250,2014,A1

41
[ 133720-60-2 ]
(phenyl)2PN(n-hexyl)P(1-benzofuran-7-yl)(phenyl) [ No CAS ]

Reference： [1]Patent: WO2014/181250,2014,A1

42
[ 133720-60-2 ]
(1-benzofuran-7-yl)(phenyl)PN(n-hex)H [ No CAS ]

Reference： [1]Patent: WO2014/181250,2014,A1

43
[ 1942-46-7 ]
[ 16537-27-2 ]
[ 133720-60-2 ]
(E)-6-(7-bromobenzofuran-2-yl)dec-5-en-5-yl pivalate [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2014,vol. 53,p. 14575 - 14579
Angew. Chem.,2014,vol. 126,p. 14803 - 14807,5

44
[ 591-20-8 ]
[ 128851-73-0 ]
[ 133720-60-2 ]

Reference： [1]Patent: WO2015/66371,2015,A1

45
[ 133720-60-2 ]
[ 95333-16-7 ]

Reference： [1]Patent: WO2015/95261,2015,A1
[2]Patent: WO2015/89842,2015,A1
[3]Patent: WO2017/155909,2017,A1
[4]Bioorganic and Medicinal Chemistry,2018,vol. 26,p. 1797 - 1809

46
[ 133720-60-2 ]
C₁₀H₁₀O₂ [ No CAS ]