[ CAS No. 69189-19-1 ]

Name: 69189-19-1|4-Bromo-1,2-bis(bromomethyl)benzene|97%
Brand: Ambeed
SKU: A940641
Price: 28.0 USD
Availability: InStock
Rating: 99 (40 reviews)

{[proInfo.proName]} ,{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]}

HazMat Fee +

There will be a HazMat fee per item when shipping a dangerous goods. The HazMat fee will be charged to your UPS/DHL/FedEx collect account or added to the invoice unless the package is shipped via Ground service. Ship by air in Excepted Quantity (each bottle), which is up to 1g/1mL for class 6.1 packing group I or II, and up to 25g/25ml for all other HazMat items.

Type	HazMat fee for 500 gram (Estimated)
Excepted Quantity	USD 0.00
Limited Quantity	USD 15-60
Inaccessible (Haz class 6.1), Domestic	USD 80+
Inaccessible (Haz class 6.1), International	USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic	USD 100+
Accessible (Haz class 3, 4, 5 or 8), International	USD 200+

2D 3D

Structure of 69189-19-1 * Storage: {[proInfo.prStorage]}

Cart0 Add to My Favorites Bulk Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

For Research Only 100K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 69189-19-1 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 69189-19-1 ]

SDS Specification

Alternatived Products of [ 69189-19-1 ]

Product Details of [ 69189-19-1 ]

CAS No. :	69189-19-1	MDL No. :	MFCD16620247
Formula :	C₈H₇Br₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	PJYGXPFKKAJUBG-UHFFFAOYSA-N
M.W :	342.85 g/mol	Pubchem ID :	12496465
Synonyms :

Calculated chemistry of [ 69189-19-1 ]

Physicochemical Properties

Num. heavy atoms :	11
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.25
Num. rotatable bonds :	2
Num. H-bond acceptors :	0.0
Num. H-bond donors :	0.0
Molar Refractivity :	59.81
TPSA :	0.0 Å²

Pharmacokinetics

GI absorption :	Low
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	Yes
CYP2D6 inhibitor :	Yes
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.74 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.8
Log Po/w (XLOGP3) :	3.73
Log Po/w (WLOGP) :	3.94
Log Po/w (MLOGP) :	4.54
Log Po/w (SILICOS-IT) :	4.51
Consensus Log Po/w :	3.9

Druglikeness

Lipinski :	1.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-4.59
Solubility :	0.00887 mg/ml ; 0.0000259 mol/l
Class :	Moderately soluble
Log S (Ali) :	-3.42
Solubility :	0.13 mg/ml ; 0.000379 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-5.73
Solubility :	0.000641 mg/ml ; 0.00000187 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.16

Safety of [ 69189-19-1 ]

Signal Word:	Danger	Class:	8
Precautionary Statements:	P260-P264-P270-P280-P301+P330+P331-P303+P361+P353-P304+P340-P305+P351+P338-P310-P363-P405-P501	UN#:	3261
Hazard Statements:	H302-H314	Packing Group:	Ⅱ
GHS Pictogram:

Application In Synthesis of [ 69189-19-1 ]

* 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 [ 69189-19-1 ]
Downstream synthetic route of [ 69189-19-1 ]

[ 69189-19-1 ] Synthesis Path-Upstream 1~3

1
[ 171011-37-3 ]
[ 69189-19-1 ]

Yield	Reaction Conditions	Operation in experiment
95%	With phosphorus tribromide In diethyl ether at 0℃; for 7 h; Reflux	To a solution of 11 (103 mg, 0.474 mM) in Et2O (3 mL) was slowly added a solution of PBr3 (0.16 mL,1.66 mM) in Et2O (0.25 mL) at 0 °C. The whole was refluxed for 7 h, poured to ice (ca 30 mL), andextracted with Et2O (20 mL × 3). The organic solutions were washed with brine (10 mL), dried, andevaporated. Purification of the residue by column chromatography (SiO2, hexane) gave 12 (154 mg,95percent) as colorless plates, mp 42-44 °C (lit [20]. mp 40-44 °C).
84%	With N-Bromosuccinimide In dichloromethane at 20℃; for 6 h;	After dissolving Compound 3 (5.2 g, 23.9 mmol) in methylene chloride (50 milliliter), followed by adding N-bromosuccinimide (12.8 g, 71.7 mmol) at room temperature, and then the resultant solution was stirred for 6 hours. Water (200 milliliter) was poured in the resultant reaction solution, and the deposited solid was washed by ethanol, and as a result, Compound 4 was obtained. Product Amount: 6.9 g, Yield: 84 percent

Reference： [1] Synlett, 2013, vol. 24, # 19, p. 2510 - 2514
[2] Patent: EP1659129, 2006, A1, . Location in patent: Page/Page column 100-101
[3] Patent: US6025370, 2000, A,
[4] Research on Chemical Intermediates, 2013, vol. 39, # 1, p. 139 - 146

2
[ 583-71-1 ]
[ 69189-19-1 ]

Yield	Reaction Conditions	Operation in experiment
93%	With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) In tetrachloromethane for 1 h; Heating / reflux	4-bromo-l,2-bis(bromomethyl)benzene (Q22). To a 1000 mL round bottom flask was added 4-brmo-oe-xylene <21) (0.0811 mol, 15.0Og), NBS (0.0426 mol, 7.580 g), 2,2 -azobisisobutyronitrile (0.00405 mol, 0.6650 g) and 500 mL of CCl₄. The reaction mixture was then heated under reflux for Ih. After this time another amount of NBS and AIBN was added and repeated over four times in total. The precipitate was filtered off from the warm reaction mixture and the filtrate concentrated. Crude material was crystallized from hexanes to form white crystals (23 g, 93percent). ¹H NMR (300 MHz, CDCl₃) δ 7.53 (d, IH, ArH, J=2.0 Hz), 7.44 (dd, IH, ArH, J-8.1 Hz, J =2.0 Hz), 7.24 (d, IH, ArH, J=8.10), 4.60 (d, 4H, CH₂, J=4.20 Hz)
56.7%	With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) In tetrachloromethane at 70℃; for 1 h;	Step A : 4-bromo-l,2-bis(bromomethyl)benzene A solution of 4-bromo-l,2-dimethylbenzene (2.0 g, 10.81 mmol) in carbon tetrachloride (70 mL) in a 250 mL round bottom flask was stirred at room temperature until all solids were dissolved. N-bromosuccinimide (4.81 g, 27.0 mmol) and 2,2'- azobis(2-methylpropionitrile) (0.044 g, 0.270 mmol) were added and mixture was heated to 70°C for 1 h. After cooling to room temperature, the mixture was filtered through celite bed. Celite bed was rinsed with carbon tetrachloride (3x50 mL). Combined filtrate was dried (sodium sulphate), filtered and concentrated under reduced pressure. The crude material was purified by combi- flash column chromatography (Column: 120 gm Red- Sep; eluent: hexane). The fractions were collected and concentrated under reduced pressure to yield 4-bromo-l,2-bis(bromomethyl) benzene (2.1 g, 56.7percent yield) as colorless gummy oil. 1H NMR (400 MHz, CDC1₃): δ 7.56-7.51 (m, 1H), 7.44-7.41 (m, 1H), 7.25- 7.22 (m, 1H), 4.59 (s, 2H), 4.578 (s, 2H).

Reference： [1] Patent: WO2008/24435, 2008, A2, . Location in patent: Page/Page column 98
[2] Journal of Organic Chemistry USSR (English Translation), 1985, p. 1418 - 1421[3] Zhurnal Organicheskoi Khimii, 1985, vol. 21, # 7, p. 1556 - 1560
[4] Patent: WO2015/103508, 2015, A1, . Location in patent: Page/Page column 102
[5] Journal of Organic Chemistry, 1979, vol. 44, # 9, p. 1519 - 1533
[6] Patent: US2014/194386, 2014, A1, . Location in patent: Paragraph 0460

3
[ 86-90-8 ]
[ 69189-19-1 ]

Reference： [1] Research on Chemical Intermediates, 2013, vol. 39, # 1, p. 139 - 146
[2] Synlett, 2013, vol. 24, # 19, p. 2510 - 2514

[ 69189-19-1 ] Synthesis Path-Downstream 1~56

1
[ 1445-69-8 ]
[ 69189-19-1 ]
[ 99878-95-2 ]

Reference： [1]Journal of Organic Chemistry USSR (English Translation),1985,p. 1418 - 1421
Zhurnal Organicheskoi Khimii,1985,vol. 21,p. 1556 - 1560

2
[ 52428-09-8 ]
[ 69189-19-1 ]
[ 123676-79-9 ]

Reference： [1]Bulletin of the Chemical Society of Japan,1994,vol. 67,p. 3067 - 3075
[2]Journal of the American Chemical Society,1989,vol. 111,p. 8979 - 8981

3
[ 583-71-1 ]
[ 69189-19-1 ]

Yield	Reaction Conditions	Operation in experiment
93%	With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); In tetrachloromethane; for 1h;Heating / reflux;	4-bromo-l,2-bis(bromomethyl)benzene (Q22). To a 1000 mL round bottom flask was added 4-brmo-oe-xylene <21) (0.0811 mol, 15.0Og), NBS (0.0426 mol, 7.580 g), 2,2 -azobisisobutyronitrile (0.00405 mol, 0.6650 g) and 500 mL of CCl4. The reaction mixture was then heated under reflux for Ih. After this time another amount of NBS and AIBN was added and repeated over four times in total. The precipitate was filtered off from the warm reaction mixture and the filtrate concentrated. Crude material was crystallized from hexanes to form white crystals (23 g, 93percent). 1H NMR (300 MHz, CDCl3) delta 7.53 (d, IH, ArH, J=2.0 Hz), 7.44 (dd, IH, ArH, J-8.1 Hz, J =2.0 Hz), 7.24 (d, IH, ArH, J=8.10), 4.60 (d, 4H, CH2, J=4.20 Hz)
56.7%	With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); In tetrachloromethane; at 70℃; for 1h;	Step A : 4-bromo-l,2-bis(bromomethyl)benzene A solution of 4-bromo-l,2-dimethylbenzene (2.0 g, 10.81 mmol) in carbon tetrachloride (70 mL) in a 250 mL round bottom flask was stirred at room temperature until all solids were dissolved. N-bromosuccinimide (4.81 g, 27.0 mmol) and 2,2'- azobis(2-methylpropionitrile) (0.044 g, 0.270 mmol) were added and mixture was heated to 70°C for 1 h. After cooling to room temperature, the mixture was filtered through celite bed. Celite bed was rinsed with carbon tetrachloride (3x50 mL). Combined filtrate was dried (sodium sulphate), filtered and concentrated under reduced pressure. The crude material was purified by combi- flash column chromatography (Column: 120 gm Red- Sep; eluent: hexane). The fractions were collected and concentrated under reduced pressure to yield 4-bromo-l,2-bis(bromomethyl) benzene (2.1 g, 56.7percent yield) as colorless gummy oil. 1H NMR (400 MHz, CDC13): delta 7.56-7.51 (m, 1H), 7.44-7.41 (m, 1H), 7.25- 7.22 (m, 1H), 4.59 (s, 2H), 4.578 (s, 2H).
	With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); In tetrachloromethane; for 18h;Reflux;	Step 1. Synthesis of 4-bromo-1,2-bis(bromomethyl)benzene To a solution of 4-bromo-1,2-dimethyl-benzene (3.7 g, 20 mmol) in carbon tetrachloride (40 mL) was added N-bromo-succinamide (7.83 g, 44 mmol). To this mixture was added azo-bis-isobutyronitrile (AIBN, 150 mg). The resulting suspension was warmed to reflux and stirred at this temperature for 3 hr. A further portion of AIBN was added (75 mg) and stirring continued for 15 hr. The reaction mixture was cooled to room temperature, filtered and the filtrate concentrated under vacuum. The residue was purified by silica chromatography (50 g silica eluted with hexane) to give a semi solid product. This material is triturated with hexane and filtered to give the title compound as a white solid.

Reference： [1]Patent: WO2008/24435,2008,A2 .Location in patent: Page/Page column 98
[2]Journal of Organic Chemistry USSR (English Translation),1985,p. 1418 - 1421
Zhurnal Organicheskoi Khimii,1985,vol. 21,p. 1556 - 1560
[3]Patent: WO2015/103508,2015,A1 .Location in patent: Page/Page column 102
[4]Journal of Organic Chemistry,1979,vol. 44,p. 1519 - 1533
[5]Patent: US2014/194386,2014,A1 .Location in patent: Paragraph 0460

4
[ 69189-19-1 ]
[ 162019-02-5 ]
[ 162019-03-6 ]

Reference： [1]Chemistry of Heterocyclic Compounds,1994,vol. 30,p. 905 - 915
Khimiya Geterotsiklicheskikh Soedinenii,1993,p. 1052 - 1062

5
[ 69189-19-1 ]
[ 123676-80-2 ]

Reference： [1]Bulletin of the Chemical Society of Japan,1994,vol. 67,p. 3067 - 3075
[2]Journal of the American Chemical Society,1989,vol. 111,p. 8979 - 8981

6
[ 69189-19-1 ]
[ 123676-81-3 ]

Reference： [1]Bulletin of the Chemical Society of Japan,1994,vol. 67,p. 3067 - 3075
[2]Journal of the American Chemical Society,1989,vol. 111,p. 8979 - 8981

7
[ 69189-19-1 ]
5-(4,7-dimethoxy-2,2'-spirobiindan-5'-yl)-13,17-diethyl-2,3,7,8,12,18-hexamethyl-21H,23H-porphine [ No CAS ]

Reference： [1]Bulletin of the Chemical Society of Japan,1994,vol. 67,p. 3067 - 3075

8
[ 69189-19-1 ]
[ 123676-88-0 ]

Reference： [1]Journal of the American Chemical Society,1989,vol. 111,p. 8979 - 8981

9
[ 69189-19-1 ]
[ 150527-38-1 ]

Yield	Reaction Conditions	Operation in experiment
59%	With sodium sulfide; In tetrahydrofuran; ethanol; water; at 70℃; for 20h;	Dissolve 4-bromo-1, 2-bis-bromomethyl-benzene (J. Org. Chef., 1418-1421, 1985; 3.42 g, 9.96 mmol) in a 2 to 1 mixture of ethanol (EtOH) and THF (1196 mL) and heat the solution to 70°C with stirring. Add a solution of Na2S. 9H2O (2.63 g, 10.96 mmol) in water (40 mL), dropwise, over 10 hours using a syringe pump. Continue to heat and stir for another 10 hours. Cool to room temperature and remove the organic solvent under reduced pressure. Add water (200 mL) to the residue and extract the aqueous layer with EtOAc (3 x 200 mL). Combine the organic layers and dry with Na2S04, filter, concentrate and purify by flash column chromatography (silica gel, hexanes) to give 1.27 g of 5-bromo-1, 3-dihydro-benzo [c] thiophene (59percent). Dissolve 5-bromo-1, 3-dihydro-benzo [c] thiophene (1. 25 g, 5.79 mmol) in methanol (25 mL) and add oxone (10.7 g, 17. 4 mmol). Stir the reaction mixture for 2 hours at 0°C and then add a 1M aqueous sodium bisulfite solution (100 mL). Stir the reaction mixture for 10 minutes and add saturated NaHCO3 solution (200 mL). Extract the aqueous layer with CH2C12 (3 x 100 mL). Combine the organic layers and dry with Na2S04, filter, concentrate and purify by flash column chromatography (silica gel, 0-5percent MeOH/CH2Cl2) to give 930 mg of 5-bromo-1, 3-dihydro-benzo [c] thiophene 2, 2-dioxide (65percent). Dissolve 5-bromo-1, 3-dihydro-benzo [c] thiophene (860 mg, 3.50 mmol) and hexamethylditin (3 eq. ) in toluene and add tetrakis (tripheuylphosphine) palladium (0) (Pd (PPh3) 4, 0.1 eq. ). Flush the flask with N2 and then heat the mixture to 120°C with stirring. Continue to heat the mixture for 5 hours and then cool to room temperature. Add water (50 mL) and extract aqueous layer with EtOAc (3 x 50 mL). Combine the organic layers and dry with Na2SO4, filter, concentrate and purify by flash chromatography (silica gel, 10-30percent EtOAc/hexane) to give 1.22 g of the title compound (100percent).
	With sodium sulphide nonahydrate; In ethanol; water; at 20℃; for 20h;	To the stirring solution ofNa2S 9W> (0.0502 mol, 12.043g) in 800 mL of ethanol was added dropwise a solution of 4- bromo-l,2-bis(bromomethyl)benzene (0.0418 mol, 14.334g) in 200 mL of ethanol in room temperature. After 2Oh a cloudy white reaction mixture was filtered and concentrated down to a 200 mL volume. Then 250 mL of ethyl acetate was added and the organic solution was washed 3x with water (125 mL) and Ix with brine (125ml). The organic phase was dried over anhydrous MgSO4 and concentrated. The crude product gave a yellow oil and was used without further purification. 1H NMR (300 MHz, CDCl3) delta 7.38 (s, IH, ArH) ppm 7.32 (dd, IH, J=1.8Hz, J=8.1Hz, ArH) ppm 7.11 (d, IH, J=8.1Hz, ArH) ppm 4.21 (dd, IH, J=1.8Hz, J=8.5Hz)

Reference： [1]Patent: WO2004/9086,2004,A1 .Location in patent: Page/Page column 28-29
[2]Patent: WO2008/24435,2008,A2 .Location in patent: Page/Page column 98

10
[ 171011-37-3 ]
[ 69189-19-1 ]

Yield	Reaction Conditions	Operation in experiment
95%	With phosphorus tribromide; In diethyl ether; at 0℃; for 7h;Reflux;	To a solution of 11 (103 mg, 0.474 mM) in Et2O (3 mL) was slowly added a solution of PBr3 (0.16 mL,1.66 mM) in Et2O (0.25 mL) at 0 °C. The whole was refluxed for 7 h, poured to ice (ca 30 mL), andextracted with Et2O (20 mL × 3). The organic solutions were washed with brine (10 mL), dried, andevaporated. Purification of the residue by column chromatography (SiO2, hexane) gave 12 (154 mg,95percent) as colorless plates, mp 42-44 °C (lit [20]. mp 40-44 °C).
84%	With N-Bromosuccinimide; In dichloromethane; at 20℃; for 6h;	After dissolving Compound 3 (5.2 g, 23.9 mmol) in methylene chloride (50 milliliter), followed by adding N-bromosuccinimide (12.8 g, 71.7 mmol) at room temperature, and then the resultant solution was stirred for 6 hours. Water (200 milliliter) was poured in the resultant reaction solution, and the deposited solid was washed by ethanol, and as a result, Compound 4 was obtained. Product Amount: 6.9 g, Yield: 84 percent
	With phosphorus tribromide; In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; diethyl ether; ethyl acetate;	(1) In 380 ml of diethyl ether was dissolved 19.0 g of 1-bromo-3,4-di(hydroxymethyl)benezene and to the solution was added 112 g of phosphorus tribromide under ice-cooling, after which the resulting mixture was allowed to stand for 3 days. The reaction mixture was added to 1,000 ml of ice water and the pH was adjusted to 7 with sodium hydrogencarbonate, followed by extraction with 1,000 ml of ethyl acetate. The organic layer thus obtained was washed with a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and then distilled under reduced pressure to remove the solvent, whereby 28.5 g of 1-bromo-3,4-di(bromomethyl)benzene were obtained as colorless crystals.

Reference： [1]Synlett,2013,vol. 24,p. 2510 - 2514
[2]Patent: EP1659129,2006,A1 .Location in patent: Page/Page column 100-101
[3]Patent: US6025370,2000,A
[4]Research on Chemical Intermediates,2013,vol. 39,p. 139 - 146

11
[ 155926-52-6 ]
[ 69189-19-1 ]
C₄₅H₃₃BrN₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%	With sodium hydroxide; N-benzyl-N,N,N-triethylammonium chloride; In water; dimethyl sulfoxide; toluene; at 80℃; for 8h;	Under the atmosphere of argon gas, Compound 1 (5 g, 10 mmol), Compound 4 (3.4 g, 10 mmol), toluene (15 milliliter), dimethylsulfoxide (15 milliliter), benzyltriethylammonium chloride (0.05 g, 0.22 mmol) and an aqueous solution (4 milliliter) of sodium hydroxide (50 percent by weight) were mixed and the resultant mixture was stirred at 80°C for 8 hours. After pouring water (100 milliliter) and toluene (100 milliliter) in the resultant reaction solution, an organic layer was separated. The layer was washed by saturated salt water, followed by drying thereof with the use of magnesium sulfate anhydride. The solvent of the organic layer was distilled and then the residue obtained was refined with silica gel column chromatography (hexane/methylene chloride) and as a result, Compound 5 was obtained. Product Amount: 3.9 g, Yield: 57 percent

Reference： [1]Patent: EP1659129,2006,A1 .Location in patent: Page/Page column 101

12
[ 69189-19-1 ]
[ 879132-40-8 ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of oxindole (363 mg, 2.73 mmol) at -78 0C in TEtaF (15 mL) was added butyllithium (2.5 M in hexanes, 2.29 mL, 5.73 mmol) drop wise, followed by the drop wise addition of tetramethylethylenediamine (0.905 mL, 6.00 mmol). The solution was stirred for 1 h at -78 0C, then a solution of 4~bromo-l,2-toe(bromomethyl)benzene [Anderson et al., J. Org. Chem. 1979, 44(9), 1519- 1533] (1.87 g, 5.45 mmol) in TEtaF (5 mL) was added drop wise. The reaction solution was stirred at -10 to -20 0C for 2 h and at ambient temperature for 16 h. The reaction mixture was partitioned between saturated NEta4CI (50 mL) and EtOAc (50 mL). The aqueous phase was further extracted with EtOAc (2 x 50 mL), and the combined organic layers were dried over Na2SO^ filtered, and concentrated under reduced pressure. The crude product was purified by silica gel chromatography, eluting with a gradient of hexanerEtOAc - 100:0 to 50:50, to give the title compound. MS: mlz = 315 (M + 1).
		To a solution of oxindole (363 mg, 2.73 mmol) at -78 0C in THF (15 mL) was added butyllithium (2.5 M in hexanes, 2.29 mL, 5.73 mmol) dropwise, followed by the dropwise addition of tetramethylethylenediamine (0.905 mL, 6.00 mmol). The solution was stirred for 1 h at -78 0C, then a solution of 4-bromo-l,2-w(bromomethyl)benzene [Anderson et al., J. Org. Chem. 1979, 44(9), 1519- 1533] (1.87 g, 5.45 mmol) in THF (5 mL) was added dropwise. The reaction solution was stirred at -10 to -20 0C for 2 h and at ambient temperature for 16 h. The reaction mixture was partitioned between <n="72"/>saturated NH4Cl (50 mL) and EtOAc (50 mL). The aqueous phase was further extracted with EtOAc (2 x 50 mL), and the combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel chromatography, eluting with a gradient of hexane:EtOAc - 100:0 to 50:50, to give the title compound. MS: mlz = 315 (M + 1).
		To a solution of oxindole (363 mg, 2.73 mmol) at -78 0C in TetaF (15 mL) was added butyllithium (2.5 M in hexanes, 2.29 mL, 5.73 mmol) dropwise, followed by the dropwise addition of tetramethylethylenediamine (0.905 mL, 6.00 mmol). The solution was stirred for 1 h at -78 0C, then a solution of 4-bromo-l,2-/.y(bromomethyl)benzene [Anderson et al., J. Org. Chem. 1979, 44(9), 1519- 1533] (1.87 g, 5.45 mmol) in TetaF (5 mL) was added dropwise. The reaction solution was stirred at -10 to -20 0C for 2 h and at ambient temperature for 16 h. The reaction mixture was partitioned between saturated NH4CI (50 mL) and EtOAc (50 mL). The aqueous phase was further extracted with EtOAc (2 x 50 mL), and the combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel chromatography, eluting with a gradient of hexane:EtOAc - 100:0 to 50:50, to give the title compound. MS: mlz = 315 (M + 1).

Reference： [1]Patent: WO2006/29153,2006,A2 .Location in patent: Page/Page column 36
[2]Patent: WO2007/61677,2007,A2 .Location in patent: Page/Page column 70-71
[3]Patent: WO2007/61692,2007,A2 .Location in patent: Page/Page column 54; 80

13
[ 69189-19-1 ]
[ 70-55-3 ]
[ 127168-85-8 ]

Yield	Reaction Conditions	Operation in experiment
	In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; N,N-dimethyl-formamide;	(2) In 70 ml of N,N-dimethylformamide was suspended 3.97 g of sodium hydride (purity: 60percent), followed by adding thereto 50 ml of a N,N-dimethylformamide solution containing 8.49 g of p-toluenesulfonamide, and the resulting mixture was stirred at 60° C. for 30 minutes. A solution of 17.0 g of <strong>[69189-19-1]1-bromo-3,4-di(bromomethyl)benzene</strong> in 50 ml of N,N-dimethylformamide was added to the reaction mixture at 60° C. and the resulting mixture was stirred at the same temperature for 1 hour. The reaction mixture obtained was added to 500 ml of ice water and the precipitate was collected by filtration and purified by a column chromatography (eluent: chloroform) to obtain 15.2 g of 5-bromo-2-(p-toluenesulfonyl)isoindoline as colorless crystals. IR (KBr) cm-1: nuSO2 1347, 1164. NMR (CDCl3) delta values: 2.39(3H, s), 4.56(4H, brs), 6.75-7.90(6H, m).
		Step 2. Synthesis of 5-bromo-2-(p-tolylsulfonyl)isoindoline To a suspension of sodium hydride (440 mg, 60percent dispersion in mineral oil, 11 mmol) in N,N-dimethylacetamide (24 mL) was added, dropwise, a solution of p-toluenesulfonamide (1.45 g, 8.5 mmol) in N,N-dimethylacetamide (8 mL) over about 5 min. The frothy solution was stirred for 1 hr at room temperature then heated to 60° C. and stirred at this temperature for 0.5 hr. To this mixture was added, dropwise a solution of <strong>[69189-19-1]4-bromo-1,2-bis(bromomethyl)benzene</strong> (2.9 g 8.4 mmol) in N,N-dimethylacetamide (6 mL). The resulting mixture was stirred for 1 hr then cooled to room temperature and stirred for 17 hr. The mixture was then diluted with ether, washed with water (2*) then brine, dried over sodium sulfate and concentrated. The residue was triturated with ethyl acetate and filtered to give the title compound as a white solid.

Reference： [1]Patent: US6025370,2000,A
[2]Patent: US2014/194386,2014,A1 .Location in patent: Paragraph 0461

15
[ 879132-48-6 ]
[ 69189-19-1 ]
[ 1189569-87-6 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate; In methanol; for 18.0833h;	INTERMEDIATE 14(d-V5-Bromo- 1 '-( [2-(trimethylsilyl)ethoxy]methvB - 1 ,3-dihvdrospirormdene-23'-pyitauolof2.3- b]pyridinl-2Yl'H)-oneTo a solution of l,2-w(bromomethyl)-4-bromobenzene (40.9 g, 132 mmol) and l-[2-(trimethylsilyl)emoxy]memyl}-13-dihydro-2i/-pyrrolo[2,3-3pyridin-2-one (31.5 g, 119 mmol, described in Intermediate 3) in MeOH (2 L) was added cesium carbonate (129 g, 397 mmol), portionwise, over 5 min. After 18 h, the mixture was concentrated to a volume of about 500 mL, then partitioned between EtOAc (1.5 L) and H2O (1 L). The organic layer was washed with H2O (1 L), then brine (500 mL), then dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of hexane:EtOAc from 100:0 to 0:100, to give the title compound. MS: mlz = 445 (M + 1).
	With caesium carbonate; In methanol; for 18h;	INTERMEDIATE 13 (+-)-5-Bromo- 1 '- {r2-(trimethylsilyl)ethoxy1methyl} - 1 ,3-dihvdrospirorindene-2,3'-pyrrolor2,3- b1pyridin1-2'(TH)-oneTo a solution of l,2-/ro(bromomethyl)-4-bromobenzene (40.9 g, 132 mmol) and l-[2-(trimethylsilyl)ethoxy]methyl}-l,3-dihydro-2H-pyrrolo[2,3-?]pyridin-2-one (31.5 g, 119 MRL-NOP-22563mmol, described in Intermediate 4) in MeOH (2 L) was added cesium carbonate (129 g, 397 mmol), portionwise, over 5 min. After 18 h, the mixture was concentrated to a volume of about 500 mL, then partitioned between EtOAc (1.5 L) and H2O (1 L). The organic layer was washed with H2O (1 L), then brine (500 mL), then dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of hexane:EtOAc - 100:0 to 0: 100, to give the title compound. MS: mlz = 445 (M + 1).

Reference： [1]Patent: WO2010/77752,2010,A1 .Location in patent: Page/Page column 90
[2]Patent: WO2009/120652,2009,A2 .Location in patent: Page/Page column 89-90

16
[ 59-48-3 ]
[ 69189-19-1 ]
[ 879132-40-8 ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of oxindole (363 mg, 2.73 mmol) at -78 0C in TEtaF (15 mL) was added butyllithium (2.5 M in hexanes, 2.29 mL, 5.73 mmol) dropwise, followed by the dropwise addition of tetramethylethylenediamine (0.905 mL, 6.00 mmol). The solution was stirred for 1 h at -78 0C, then a solution of 4-bromo-l,2-"(bromomethyl)benzene [Anderson et ah, J. Org. Chem. 1979, 44(9), 1519- 1533] (1.87 g, 5.45 mmol) in TEtaF (5 mL) was added dropwise. The reaction solution was stirred at -10 to -20 0C for 2 h and at ambient temperature for 16 h. The reaction mixture was partitioned between saturated NH4Cl (50 mL) and EtOAc (50 mL). The aqueous phase was further extracted with EtOAc (2 x 50 mL), and the combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel chromatography, eluting with a gradient of hexane:EtOAc - 100:0 to 50:50, to give the title compound. MS: mlz = 315 (M + 1).
		To a solution of oxindole (363 mg, 2.73 mmol) at -78 0C in TEtaF (15 mL) was added butyllithium (2.5 M in hexanes, 2.29 mL, 5.73 mmol) drop wise, followed by the drop wise addition of tetramethylethylenediamine (0.905 mL, 6.00 mmol). The solution was stirred for 1 h at -78 0C, then a solution of 4-bromo-l,2-Z>/s(bromomethyl)benzene [Anderson et al, J. Org. Chem. 1979, 44(9), 1519- 1533] (1.87 g, 5.45 mmol) in TEtaF (5 mL) was added drop wise. The reaction solution was stirred at -10 to -20 °C for 2 h and at ambient temperature for 16 h. The reaction mixture was partitioned between saturated NH4Cl (50 mL) and EtOAc (50 mL). The aqueous phase was further extracted with EtOAc (2 x 50 mL), and the combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel chromatography, eluting with a gradient of hexane: EtOAc - 100:0 to 50:50, to give the title compound. MS: mlz = 315 (M + 1).
		To a solution of oxindole (363 mg, 2.73 mmol) at -78 0C in TEtaF (15 mL) was added butyllithium (2.5 M in hexanes, 2.29 mL, 5.73 mmol) drop wise, followed by the drop wise addition of tetramethylethylenediamine (0.905 mL, 6.00 mmol). The solution was stirred for 1 h at -78 0C, then a solution of 4-bromo-l,2-toe(bromomethyl)benzene [Anderson et al., J. Org. Chem. 1979, 44(9), 1519- 1533] (1.87 g, 5.45 mmol) in TEtaF (5 mL) was added drop wise. .The reaction solution was stirred at -10 to -20 0C for 2 h and at ambient temperature for 16 h. The reaction mixture was partitioned between saturated NELjCl (50 mL) and EtOAc (50 mL). The aqueous phase was further extracted with EtOAc (2 x 50 mL), and the combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel chromatography, eluting with a gradient of hexane:EtOAc - 100:0 to 50:50, to give the title compound. MS: mlz = 315 (M + 1).

To a solution of oxindole (363 mg, 2.73 mmol) at -78 0C in TetaF (15 mL) was added butyUithium (2.5 M in hexanes, 2.29 mL, 5.73 mmol) dropwise, followed by the dropwise addition of <n="89"/>tetramethylethylenediamine (0.905 mL, 6.00 mmol). The solution was stirred for 1 h at -78 0C, then a solution of 4-bromo-l,2-6/s(bromomethyl)benzene [Anderson et al., J. Org. Chem. 1979, 44(9), 1519- 1533] (1.87 g, 5.45 mmol) in THF (5 mL) was added dropwise. The reaction solution was stirred at -10 to -20 0C for 2 h and at ambient temperature for 16 h. The reaction mixture was partitioned between saturated NBUCl (50 mL) and EtOAc- (50 mL). The aqueous phase was further extracted with EtOAc (2 x 50 mL), and the combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel chromatography, eluting with a gradient of hexane:EtOAc - 100:0 to 50:50, to give the title compound. MS: m/z = 315 (M + 1).

Reference： [1]Patent: WO2006/31491,2006,A2 .Location in patent: Page/Page column 35; 56
[2]Patent: WO2006/31513,2006,A2 .Location in patent: Page/Page column 35; 42
[3]Patent: WO2006/31610,2006,A2 .Location in patent: Page/Page column 36; 50
[4]Patent: WO2007/61696,2007,A2 .Location in patent: Page/Page column 62; 87-88

17
[ 1383854-78-1 ]
[ 69189-19-1 ]
[ 1383854-76-9 ]

Reference： [1]Research on Chemical Intermediates,2013,vol. 39,p. 139 - 146

18
[ 69189-19-1 ]
[ 130-15-4 ]
[ 126963-18-6 ]

Reference： [1]Research on Chemical Intermediates,2013,vol. 39,p. 139 - 146

19
[ 86-90-8 ]
[ 69189-19-1 ]

Reference： [1]Research on Chemical Intermediates,2013,vol. 39,p. 139 - 146
[2]Synlett,2013,vol. 24,p. 2510 - 2514

20
[ 69189-19-1 ]
2-bromo-tetracene [ No CAS ]

Reference： [1]Research on Chemical Intermediates,2013,vol. 39,p. 139 - 146

21
[ 1352928-76-7 ]
[ 69189-19-1 ]
[ 1383854-75-8 ]

Reference： [1]Research on Chemical Intermediates,2013,vol. 39,p. 139 - 146

22
C₁₀H₂₀N₄ [ No CAS ]
[ 69189-19-1 ]
C₁₈H₂₅BrN₄ [ No CAS ]

Reference： [1]Journal of Porphyrins and Phthalocyanines,2014,vol. 18,p. 35 - 48

23
[ 69189-19-1 ]
9a,9b-dimethyl-octahydro-1,3a,6a,9-tetraaza-phenalene [ No CAS ]
C₁₉H₂₇BrN₄ [ No CAS ]

Reference： [1]Journal of Porphyrins and Phthalocyanines,2014,vol. 18,p. 35 - 48

24
[ 773837-37-9 ]
[ 69189-19-1 ]
4-bromo-1,2-bis(cyanomethyl)benzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	In ethanol; water; at 0℃; for 0.5h;Inert atmosphere; Reflux;	A solution of NaCN (1.32 g, 27.0 mM) in H2O (20 mL) was added to a solution of 12 (3.70 g, 10.8 mM)in EtOH (75 mL) at 0 °C under argon and the whole was refluxed for 0.5 h and evaporated. After theresidue was dissolved in AcOEt (30 mL) the mixture was partitioned with H2O (20 mL). The aqueoussolution was extracted with AcOEt (30 mL × 3). The organic solutions were washed with brine (20 mL),dried (MgSO4), and evaporated. Purification of the residue by column chromatography (SiO2, hexane :AcOEt = 3 : 1) gave 18 (2.10 g, 83percent) as yellow plates, mp 72-73 °C.

Reference： [1]Synlett,2013,vol. 24,p. 2510 - 2514

25
[ 69189-19-1 ]
4-bromo-1,2-bis(aminomethyl)benzene dihydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%		A solution of NaN3 (125 mg, 1.72 mM) in H2O (1 mL) was added to a solution of 12 (269 mg, 0.784mM) in THF-EtOH-H2O (4 : 3 : 1) (16 mL) at rt and the whole was refluxed for 1.5 h. After completion of N2 evolution by slow addition (10 min) of PPh3 (476 mg, 1.72 mM), the mixture was refluxed for 0.5h and cooled to 0 °C. After addition of conc HCl aq (1.5 mL), the mixture was refluxed for 2 h andevaporated. The residue was washed with AcOEt (20 mL × 5) and dissolved in 10percent HCl aq (5 mL),made alkaline (pH ca 11) by addition of 20percent NaOH aq, and extracted with Et2O (15 mL × 5). Theorganic solutions were washed with brine (10 mL), dried (K2CO3), and concentrated (to ca 10 mL). Theconcentrate was stirred with sat solution of HCl in Et2O (5 mL) for 0.5 h and filtered to give 13·2HCl(198 mg, 88percent) as colorless solids, mp 281-288 °C.

Reference： [1]Synlett,2013,vol. 24,p. 2510 - 2514

26
[ 69189-19-1 ]
[ 1609568-26-4 ]

Reference： [1]Synlett,2013,vol. 24,p. 2510 - 2514

27
[ 69189-19-1 ]
[ 1609574-30-2 ]

Reference： [1]Synlett,2013,vol. 24,p. 2510 - 2514

28
[ 69189-19-1 ]
[ 1609574-33-5 ]

Reference： [1]Synlett,2013,vol. 24,p. 2510 - 2514

29
[ 69189-19-1 ]
[ 1609574-36-8 ]

Reference： [1]Synlett,2013,vol. 24,p. 2510 - 2514

30
[ 69189-19-1 ]
3-[(3,4-bisaminoethyl)phenyl]propan-1-ol dihydrochloride [ No CAS ]

Reference： [1]Synlett,2013,vol. 24,p. 2510 - 2514

31
[ 69189-19-1 ]
3-[3,4-bis(1,3-dimethylimidazolin-2-ylideneaminoethyl)phenyl]propan-1-ol [ No CAS ]

Reference： [1]Synlett,2013,vol. 24,p. 2510 - 2514

32
[ 69189-19-1 ]
[ 127168-84-7 ]