10133-22-9|5-(Bromomethyl)benzo[b]thiophene| Ambeed

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Structure of 10133-22-9

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Quality Control of [ 10133-22-9 ] Purity: 97% SDS Specification

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Product Details of [ 10133-22-9 ]

CAS No. :	10133-22-9
Formula :	C₉H₇BrS
M.W :	227.12
SMILES Code :	BrCC1=CC=C2C(C=CS2)=C1
MDL No. :	MFCD18451809
InChI Key :	FOQVMHRXEHFCNW-UHFFFAOYSA-N
Pubchem ID :	11160498

Safety of [ 10133-22-9 ]

GHS Pictogram:
Signal Word:	Danger
Hazard Statements:	H302-H314
Precautionary Statements:	P264-P270-P271-P280-P303+P361+P353-P304+P340-P305+P351+P338-P310-P330-P331-P363-P403+P233-P501
Class:	8
UN#:	3261
Packing Group:	Ⅱ

Computational Chemistry of [ 10133-22-9 ] Show Less

Physicochemical Properties

Num. heavy atoms	11
Num. arom. heavy atoms	9
Fraction Csp3	0.11
Num. rotatable bonds	1
Num. H-bond acceptors	0.0
Num. H-bond donors	0.0
Molar Refractivity	54.66
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	28.24 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.48
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	3.5
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	3.64
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.	3.41
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	4.66
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	3.54

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-3.99
Solubility	0.0231 mg/ml ; 0.000102 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.	-3.78
Solubility	0.038 mg/ml ; 0.000167 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	-4.61
Solubility	0.00563 mg/ml ; 0.0000248 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	Yes
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-5.2 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	1.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
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)	1.98

Application In Synthesis of [ 10133-22-9 ]

* 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 [ 10133-22-9 ]

[ 10133-22-9 ] Synthesis Path-Downstream 1~35

1
[ 14315-14-1 ]
[ 10133-22-9 ]

Yield	Reaction Conditions	Operation in experiment
76%	With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); In tetrachloromethane; for 3h;Heating / reflux;	5-Methylbenzo (b) thiophene (0.37g, 2. 48mmol) is dissolved in carbon tetrachloride (4ml) and treated with N-bromosuccinimide (0.46g, 2. 58mmol) and 2,2'-azobis-isobutyronitrile (lOmg). The mixture is stirred and warmed under reflux for 3h and then left to cool to room temperature overnight. The mixture is filtered and the filtrate evaporated to dryness in vacuum at 40C. The residual brown oil is treated with iso-hexane and warmed until it dissolves, before leaving to cool. The mixture is chilled and scratched until crystalline solid forms. The temperature is allowed to warm back up to room temperature and then the solid is isolated by filtration. The solid is then washed with more iso-hexane. The filtrate is concentrated to half the volume and then chilled again with scratching. Solid is re-formed and isolated by filtration, and air drying. The desired product is formed as a white solid, this material is used as'seed'crystals. The procedure is then repeated on a larger scale. Thus 5-methylbenzo (b) thiophene (51.3g, 0. 35mol) is dissolved in carbon tetrachloride (540ml), N-Bromosuccinimide (63.8g, 0. 36mol, 1.04eq), 2,2'-azobis-isobutyronitrile (0.4g) are then added. The crude product is crystallised from iso-hexane (no heating) using'seed'crystals. The material immediately formed and is isolated by filtration and dried. This material is dried further in vacuo at room temperature to give the desired product (69.62g) which is recrystallised from hot iso-hexane and left to cool. The solid is isolated by filtration and dried in vacuo at room temperature to give the required product (59.6g, 76%) ; 1H NMR (300 MHz, CDC13) : 8= 7. 88-7. 81 (2 H, m), 7.50-7. 45 (1 H, m), 7.41-7. 35 (1 H, m), 7.34-7. 30 (1 H, m) and 4.65 (2 H, s).
41%	With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); In tetrachloromethane; for 3h;Reflux;	5-Methylbenzo[b]thiophene (500 mg, 3.37 mmol), 108 N-bromosuccinimide (560 mg, 3.37 mmol) and 109 AIBN (28 mg, 0.05 mmol) were dissolved in 110 carbon tetrachloride (45 mL). The reaction mixture was refluxed for 3 hours. The reaction mixture was cooled, and the suspension was filtered. The filtrate was concentrated under reduced pressure. The resulting residue was purified on an ISCO chromatography (100% hexane) to give the 114 product as a white solid (312 mg, 41%); 1H NMR (300 MHz) (CDCl3) delta 7.87-7.85 (m, 2H), 7.48 (d, J=6 Hz, 1H), 7.39 (dd, J=8 Hz, J=2 Hz, 1H), 7.32 (dd, J=6 Hz, 1H), 4.66 (s, 2H).
	With N-Bromosuccinimide;	5-Bromomethylbenzo[b]thiophene was prepared from 5-methylbenzo[b]thiophene and N-bromosuccinimide as in Example 6 except that the reaction was refluxed 15 hours. The title compound was prepared as in example 7 from the corresponding beta-keto ester and anhydrous hydrazine.

	With N-Bromosuccinimide;	5-Bromomethylbenzo[b]thiophene was prepared from 5-methylbenzo[b]thiophene and N-bromosuccinimide as in Example 1 except that the reaction was refluxed 15 hours. The title compound was prepared as in example 1 from the corresponding beta-keto ester and anhydrous hydrazine.
	With N-Bromosuccinimide; dibenzoyl peroxide;	EXAMPLE 123 N-?5-[(R)-1-(Hydroxy-2-[[1-(benzo[b]thiophen-5-yl)-2-phenylethyl]amino]ethyl)-2-hydroxyphenyl]methanesulfonamide, trifluoroacetate salt STR176 A. 5-Benzo[b]thiophenylcarboxaldehyde A mixture of 5-methylbenzo[b]thiophene (3.8 g, 25.6 mmol), NBS (4.7 g, 27 mmol), and benzoyl peroxide (310 mg, 1.3 mmol) were refluxed one hour in CCl4 (100 mL) while being irradiated with a sunlamp. Upon completion, the reaction was cooled, diluted with Et2 O, filtered and concentrated to yield 5.8 g of 5-bromomethylbenzo[b]thiophene.
	With N-Bromosuccinimide; In tetrachloromethane; for 4h;Heating / reflux;	A solution containing 5-methylbenzo[b]thiophene (37 g), N-bromosuccinimide (46 g), and tetrachloromethane (400 ml) was refluxed for 4 h, cooled, and filtered. The filtrate was evaporated and the resultant residue crystallised from hexane to give the subtitle compound (40 g).
	With N-Bromosuccinimide; 1,1'-azobis(1-cyanocyclohexanenitrile); In tetrachloromethane; for 6h;Inert atmosphere; Reflux;	Preparative Example 485-(BROMOMETHYL)-1-BENZOTHIOPHENEN-Bromosuccinimide (4.53 g, 25.4 mmol, 1.20 eq) and 1,1'-azobis(cyclohexane-carbonitrile) (260 mg, 1.06 mmol, 0.05 eq) were added to a solution of 5-methyl-1-benzothiophene (3.14 g, 21.2 mmol, 1 eq) in carbon tetrachloride (90 mL) under nitrogen. The reaction mixture was heated under reflux and after 3 h a further amount of 1,1'-azobis(cyclohexane-carbonitrile) (260 mg, 1.06 mmol, 0.05 eq) was added. After an additional 3 h of heating under reflux, the reaction mixture was cooled down to room temperature and filtered. The filtrate was transferred to a separatory funnel, washed with a saturated aqueous solution of sodium bicarbonate, and the organic phase was dried over sodium sulfate, filtered and concentrated. Purification by flash chromatography on silica gel (ethyl acetate/hexane, 2:98 to 4:96) afforded 5-(bromomethyl)-1-benzothiophene.
	With N-Bromosuccinimide; In ethyl acetate; at 30℃; for 0.0333333h;Flow reactor; Irradiation;	A solution of 1.1 g of 5-methyl-1-benzothiophene (Compound B) in 3.3 mL of ethyl acetate was prepared (solution I). Separately, a solution of 0.66 g of NBS in 25 mL of ethyl acetate was prepared (solution II). The solutions I and II were each fed by a syringe pump to an in-line mixer connected to a FEP tube having an inner diameter of 0.5 mm, where the flow rates of the solutions I and II were adjusted so that the amount of NBS was 1.1 equivalents based on that of Compound B. After mixing the solutions I and II in the in-line mixer, the FEP tube was irradiated with a high pressure mercury lamp (UM-102, manufactured by Ushio Inc.). The average residence time the solution takes to pass through the section irradiated with the high-pressure mercury lamp was set to 2 minutes. Further, the in-line mixer and a high pressure mercury lamp wrapped with the reaction tube were immersed in a water bath and the water temperature was held at 30 C. The obtained reaction solution was measured by HPLC, and it was determined that the peak area ratio of Compound A was 90%. The peak area ratios of Compounds B, C and D are shown in Table 2.

References: [1]Patent: WO2005/92885,2005,A1 .Location in patent: Page/Page column 56; 57.
[2]Patent: US2019/31624,2019,A1 .Location in patent: Paragraph 0454-0455.
[3]Journal of Medicinal Chemistry,1991,vol. 34,p. 65 - 73.
[4]Patent: US5183825,1993,A .
[5]Patent: US5194435,1993,A .
[6]Patent: US5776983,1998,A .
[7]Patent: US2003/199571,2003,A1 .Location in patent: Page/Page column 7.
[8]Patent: US2010/279983,2010,A1 .Location in patent: Page/Page column 27.
[9]Patent: US2019/119242,2019,A1 .Location in patent: Paragraph 0125; 0138.

2
[ 10133-22-9 ]
[ 216873-06-2 ]
[ 130219-90-8 ]
[ 130219-90-8 ]

References: [1]Journal of Medicinal Chemistry,1991,vol. 34,p. 65 - 73.

3
[ 10133-22-9 ]
[ 372-31-6 ]
2-Benzo[b]thiophen-5-ylmethyl-4,4,4-trifluoro-3-oxo-butyric acid ethyl ester [ No CAS ]

References: [1]Journal of Medicinal Chemistry,1995,vol. 38,p. 617 - 628.

4
[ 10133-22-9 ]
[ 348080-83-1 ]

References: [1]Synthetic Communications,2003,vol. 33,p. 627 - 632.

5
[ 10133-22-9 ]
[ 17381-54-3 ]

References: [1]Journal of Medicinal Chemistry,1997,vol. 40,p. 1049 - 1062.

6
[ 10133-22-9 ]
[ 96803-30-4 ]

References: [1]Journal of Medicinal Chemistry,1997,vol. 40,p. 1049 - 1062.

7
[ 10133-22-9 ]
[ 188111-49-1 ]

References: [1]Journal of Medicinal Chemistry,1997,vol. 40,p. 1049 - 1062.

8
[ 10133-22-9 ]
[ 188111-50-4 ]

References: [1]Journal of Medicinal Chemistry,1997,vol. 40,p. 1049 - 1062.

9
[ 10133-22-9 ]
2-Benzo[b]thiophen-5-yl-N-((R)-5-methoxy-1,2,3,4-tetrahydro-naphthalen-1-ylmethyl)-N-methyl-acetamide [ No CAS ]

References: [1]Journal of Medicinal Chemistry,1997,vol. 40,p. 1049 - 1062.

10
[ 10133-22-9 ]
N-[2-(Benzothiophen-5-yl)ethyl]-N-[(R)-(+)-5-methoxy-1,2,3,4-tetrahydronaphthalen-1-ylmethyl]-N-methylamine [ No CAS ]

References: [1]Journal of Medicinal Chemistry,1997,vol. 40,p. 1049 - 1062.

11
[ 10133-22-9 ]
[2-(1,1-Dioxo-1H-1λ⁶-benzo[b]thiophen-5-yl)-ethyl]-((R)-5-methoxy-1,2,3,4-tetrahydro-naphthalen-1-ylmethyl)-methyl-amine [ No CAS ]

References: [1]Journal of Medicinal Chemistry,1997,vol. 40,p. 1049 - 1062.

12
[ 179556-97-9 ]
[ 10133-22-9 ]
[ 866328-90-7 ]

Yield	Reaction Conditions	Operation in experiment
100%	With potassium carbonate; In acetonitrile; for 16h;Heating / reflux;	To a solution of 5-bromomethyl-benzo [b] thiophene (1. 55g, 6.8mmol, 2.4 eq) and 1,1- dimethylethyl 4-[(2-methylpropyl) amino] piperidine-1-carboxylate (0. 71g, 2. 8mmol, 1 eq) in acetonitrile (25ml) is added potassium carbonate (0.62g, 4.4mmol, 1.6eq). The mixture is heated to reflux for 16 hours. The solution is filtered and the solvent removed in vacuo. The resulting oil is purified on a 40g Redisep column using a gradient of 0-20% ethyl acetate/iso-hexane to give 1, 1-dimethylethyl 4-f [ (1-benzothienyl-5-yl) methyl]- (2- methylpropyl) amino}-piperidine-l-carboxylate as an oil (1.12 g, 100 %). mass spectrum (LCMS): m/z= 403.5 (M++1), Rt= 3.38 (6 min gradient) ; 1H NMR (300 MHz, CDC13) : 8= 7. 80-7. 60 (2 H, m), 7.37-7. 33 (1 H, m), 7.32-7. 26 (1 H, m), 7.25-7. 20 (1 H, m), 4.17- 3.94 (2 H, m), 3.65 (2 H, s), 2. 65-2. 36 (3 H, m), 2.24-2. 10 (2 H, d), 1.71-1. 28 (5 H, m), 1.38 (9 H, s), 0.88-0. 69 (6 H, d).
46%	With potassium carbonate; In acetonitrile;	Add potassium carbonate (0.619 g, 4.4 mmol, 1.6 eq) followed by 5-bromomethyl- benzo [b] thiophene (17.7 g, 78 mmol, 1 eq) in one portion to a stirred solution of 1,1- dimethylethyl 4- [ (2-methylpropyl) amino] piperidine-1-carboxylate (20 g, 78 mmol, 1 eq) in acetonitrile (400 ml). Cool, add water (250 ml) then filter. Wash the solid with ice cold acetonitrile and leave to dry on sinter for 1 hr. Purify on a 330 g Redisep column (20 g per column) using a gradient of 0-40% Ethyl acetate/iso-hexane to give 1,1- dimethylethyl 4- { [ (l-benzothienyl-5-yl] methyl]- (2-methylpropyl) amino}-piperidine-1- carboxylate (7.64 g, 46 %) as yellow solid. LCMS Rt= 3.38 (6 min gradient) M++1 : 403.5. 1H NMR (300 MHz, CDC13) 6 ppm 7.80-7. 60 (2 H, m), 7.37-7. 33 (1 H, m), 7.32- 7.26 (1 H, m), 7.25-7. 20 (1 H, m), 4.17-3. 94 (2 H, m), 3.65 (2 H, s), 2.65-2. 36 (3 H, m), 2.24-2. 10 (2 H, d), 1.71-1. 28 (5 H, m), 1.38 (9 H, s), 0.88-0. 69 (6 H, d).

References: [1]Patent: WO2005/92885,2005,A1 .Location in patent: Page/Page column 57; 58.
[2]Patent: WO2005/92885,2005,A1 .Location in patent: Page/Page column 59.

13
[ 2472-88-0 ]
[ 10133-22-9 ]
[ 1643-19-2 ]
tetrabutylammonium benzo[b]thiophene-5-methanesulfonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; sodium sulfite; In dichloromethane; water;	A mixture containing <strong>[10133-22-9]5-bromomethylbenzo[b]thiophene</strong> (40 g), tetra-n-butylammonium hydrogen sulfate (135 g), sodium hydroxide (14 g), sodium sulfite (45 g), dichloromethane (300 ml), and water (300 ml) was stirred vigorously overnight. The organic layer was dried (MgSO4), evaporated, dissolved in THP (130 ml), re-evaporated, and dissolved again in THF (130 ml). Addition of ether (200 ml) gave the crystalline subtitle compound containing an equimolar amount of tetra-n-butylammonium bromide (132 g).

References: [1]Patent: US2003/199571,2003,A1 .Location in patent: Page/Page column 7.

14
[ 14315-14-1 ]
[ 94-36-0 ]
[ 10133-22-9 ]

Yield	Reaction Conditions	Operation in experiment
6.37 g (83%)	With N-Bromosuccinimide; In tetrachloromethane; n-heptane; ethyl acetate;	Step 1 5-Bromomethylbenzo[b]thiophene A mixture of 5-methylbenzo[b]thiophene (5.0 g, 33.7 mmol), N-bromosuccinimide (5.7 g, 32.0 mmol) and dibenzoylperoxide (0.25 g, 1.01 mmol) in tetrachloromethane was heated to reflux for 2 hours. It was cooled to room temperature and left for 16 hours. The solid was filtered off. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (300 g), using ethyl acetate/heptane (1:10) as eluent, to give 6.37 g (83%) of 5-bromomethylbenzo[b]thiophene. 1H NMR (CDCl3): delta4.60 (s, 2 H), 7.28 (d, 1 H), 7.35 (d, 1 H), 7.45 (d, 1 H), 7.70 (m, 2 H).

References: [1]Patent: US2002/58659,2002,A1 .

15
[ 10133-22-9 ]
benzo[b]thiophen-5-ylmethanamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.40 g (19%)	With ammonium hydroxide; In n-heptane; ethyl acetate; N,N-dimethyl-formamide;	Step 2 ((Benzo[b]thiophen-5-yl)methyl)amine A solution of <strong>[10133-22-9]5-bromomethylbenzo[b]thiophene</strong> (3.0 g, 13.20 mmol) in DMF (15 ml) was added to a solution of 25% aqueous ammonia (10 ml, 132 mmol) in DMF (10 ml). The reaction mixture was stirred for 4 hours at room temperature. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (40 g), using first ethyl acetate/heptane (1:1; 60 ml) and subsequently DCM/methanol/25% aqueous ammonia (100:10:1) as eluent, to give 0.40 g (19%) of ((benzo[b]thiophen-5-yl)methyl)amine. 1H NMR (DSMO-d6) delta3.85 (s, 2 H), 7.40 (m, 2 H), 7.75 (d, 1 H), 7.85 (s, 1 H), 7.92 (d, 1 H).

References: [1]Patent: US2002/58659,2002,A1 .

16
tert-butyl (3RS,4RS)-3-hydroxy-4-[4-[3-(2-phenyl-[ 1,3 ]dioxolan-2-yl)-propoxy]-phenyl]-piperidine-1-carboxylate [ No CAS ]
[ 10133-22-9 ]
tert-butyl (3RS,4RS)-3-(benzo[b]thiophen-5-ylmethoxy)-4-{4-[3-(2-phenyl-[1,3]dioxolan-2-yl)-propoxy]-phenyl}-piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		The following compounds were obtained in an analogous manner to that described in Example 46(d)-(e) and, respectively, 3(c)-(e): 1)--From tert-butyl (3RS,4RS)-3-hydroxy-4-[4-[3-(2-phenyl-[1,3]dioxolan-2-yl)-propoxy]-phenyl]-piperidine-1-carboxylate by alkylation with <strong>[10133-22-9]5-bromomethyl-benzo[b]thiophene</strong> there was obtained tert-butyl (3RS,4RS)-3-(benzo[b]thiophen-5-ylmethoxy)-4-{4-[3-(2-phenyl-[1,3]dioxolan-2-yl)-propoxy]-phenyl}-piperidine-1-carboxylate, MS: 630 (M+H)+, as a light yellow resin.

References: [1]Patent: US6051712,2000,A .

17
[ 18441-43-5 ]
[ 10133-22-9 ]
[ 188862-35-3 ]

Yield	Reaction Conditions	Operation in experiment
	With N-Bromosuccinimide; In tetrachloromethane;	The 5-bromomethyl-benzo[b]furan used as the alkylating agent was prepared as follows: By brominating 5-methyl-benzo[b]furan[Synth. Commun. 19, 257(1989)] with N-bromosuccinimide in carbon tetrachloride in an analogous manner to the procedure for the preparation of 5-bromomethyl-benzo[b]thiophene [J. Med. Chem. 34(1), 65(1991)] from 5-methyl-benzo[b]thiophene there was obtained 5-bromomethyl-benzo[b]furan as a light yellow solid; MS: 210, 212 (M)+.

References: [1]Patent: US6051712,2000,A .

18
[ 42270-37-1 ]
[ 10133-22-9 ]
[ 56607-36-4 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; In N-methyl-acetamide; ethanol; toluene;	First method A solution of 8.6 g (0.0506 mole) of 1-(2-thiazolyl) piperazine and 5.75 g (0.0253 mole) of <strong>[10133-22-9]5-bromomethyl benzo [b ] thiophene</strong> (MP 37 C) in 145 ml of anhydrous toluene containing 5 ml of dimethylformamide was stirred at 25 for 24 hours. At the completion of the reaction, the thiazolyl piperazine hydrobromide which had formed was filtered off and the solvent was evaporated from the filtrate under reduced pressure. There were obtained 10 g of a yellow oil which was treated with 50 ml of a 2N hydrochloric acid solution. The acid solution was washed with ether and the base was salted out with an excess of potassium carbonate. There were obtained 6 g of a crude crystallized product, which was recrystallized in 20 ml of ethanol to give 5 g of 1-(5-benzo [b] thienylmethyl)-4-(2-thiazolyl) piperazine as beige crystals melting at 80-82 C.

References: [1]Patent: US3954765,1976,A .

Yield	Reaction Conditions	Operation in experiment
		PREPARATION 3 5-Bromomethylbenzo[b]thiophene Refer to Chart A (conversion of LXXXVII to XCII). The titled compound is prepared from the compound of Preparation 1 using the procedure of Y. Matsuki, et al., Nippon Kugaku Zasshi 87:186 (1966). The compound has a melting point of 97 C.

20
[ 862791-12-6 ]
[ 10133-22-9 ]
[ 1198791-03-5 ]
[ 1198791-04-6 ]

References: [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 191 - 200.

21
[ 110-91-8 ]
[ 10133-22-9 ]
[ 959144-98-0 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In dimethyl sulfoxide; at 20℃; for 18h;Inert atmosphere;	Preparative Example 50PREPARATION OF 4-(1-BENZOTHIEN-5-YLMETHYL)MORPHOLINETo a stirred solution of <strong>[10133-22-9]5-(bromomethyl)-1-benzothiophene</strong> (2.3 g, 10.1 mmol, 1 eq) in dimethylsulfoxide (10 mL) were added morpholine (0.97 mL, 11 mmol, 1.1 eq) and diisopropylethylamine (2.6 mL, 15.2 mmol, 1.5 eq). The solution was stirred at room temperature under nitrogen for 18 h then water (200 mL) was added. The solution was made alkaline (pH 12) with aqueous sodium hydroxide (1N) and the aqueous phase was extracted twice with ethyl acetate. Combined organic phases were washed with brine, dried over sodium sulfate and concentrated. Purification by flash chromatography on silica gel (methanol/dichloromethane, 1:99) afforded 4-(1-benzothien-5-ylmethyl)morpholine.1H NMR (400 MHz, CDCl3) delta (ppm): 7.84 (d, J=8.0 Hz, 1H), 7.79 (s, 1H), 7.45 (d, J=5.6 Hz, 1H), 7.37 (d, J=8.0 Hz, 1H), 7.32 (d, J=5.6 Hz, 1H), 3.82-3.72 (m, 4H), 3.72-3.63 (bs, 2H), 2.54 (bs, 4H); MS m/z 234 (M+1).

References: [1]Patent: US2010/279983,2010,A1 .Location in patent: Page/Page column 28.

22
[ 50-00-0 ]
[ 10133-22-9 ]
[ 1033775-44-8 ]

Yield	Reaction Conditions	Operation in experiment
		Preparative Example 49PREPARATION OF 5-VINYL-1-BENZOTHIOPHENETriphenylphosphine (1.20 g, 4.58 mmol) and <strong>[10133-22-9]5-(bromomethyl)-1-benzothiophene</strong> (1.00 g, 4.40 mmol) in toluene (50 mL) was heated under reflux for 2 h. The mixture was then cooled and the resulting white crystalline precipitate was isolated by suction filtration, rinsed with a small amount of hexanes, and dried in vacuo. The solid was suspended in aqueous formaldehyde (37%, 20 mL) and aqueous sodium hydroxide (3M, 10 mL) was added dropwise. The resulting mixture was stirred for 3 h at r.t. It was then extracted with hexanes, dried (MgSO4), and concentrated under reduced pressure. Column chromatography of the residue (hexanes) afforded the product.1H NMR (400 MHz, CDCl3) delta (ppm): 7.83-7.80 (m, 2H); 7.48-7.42 (m, 2H); 7.31 (dd, J=5.2, 0.8, 1H); 6.83 (dd, J=17.0, 11.0, 1H); 5.82 (d, J=17.4, 1H); 5.28 (d, J=11.0, 1H).

References: [1]Patent: US2010/279983,2010,A1 .Location in patent: Page/Page column 27-28.

23
[ 862791-12-6 ]
[ 10133-22-9 ]
[ 1198791-03-5 ]
C₃₇H₄₈O₅S₂Si₂ [ No CAS ]