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Quality Control of [ 158690-56-3 ] Purity: 97% SDS Specification

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Product Details of [ 158690-56-3 ]

CAS No. :	158690-56-3
Formula :	C₁₄H₂₁NO₅S
M.W :	315.39
SMILES Code :	O=S(C1=CC=C(C)C=C1)(OCCNC(OC(C)(C)C)=O)=O
MDL No. :	MFCD07776965
InChI Key :	OWNIGLWHXOENAA-UHFFFAOYSA-N
Pubchem ID :	10781634

Safety of [ 158690-56-3 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Computational Chemistry of [ 158690-56-3 ] Show Less

Physicochemical Properties

Num. heavy atoms	21
Num. arom. heavy atoms	6
Fraction Csp3	0.5
Num. rotatable bonds	8
Num. H-bond acceptors	5.0
Num. H-bond donors	1.0
Molar Refractivity	78.94
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	90.08 ?2

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	3.26
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	2.27
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	3.31
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	2.15
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	1.43
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.48

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.91
Solubility	0.389 mg/ml ; 0.00123 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.	-3.8
Solubility	0.0502 mg/ml ; 0.000159 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	-4.19
Solubility	0.0202 mg/ml ; 0.0000641 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	No
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.	-6.61 cm/s

Druglikeness

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

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	1.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<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)	3.01

Application In Synthesis of [ 158690-56-3 ]

* 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 [ 158690-56-3 ]
Downstream synthetic route of [ 158690-56-3 ]

[ 158690-56-3 ] Synthesis Path-Upstream 1~1

1
[ 158690-56-3 ]
[ 97308-23-1 ]

References: [1] Organic Letters, 2013, vol. 15, # 8, p. 1946 - 1949.
[2] Angewandte Chemie - International Edition, 2018, vol. 57, # 34, p. 10980 - 10984[3] Angew. Chem., 2018, vol. 130, # 34, p. 11146 - 11150,5.

[ 158690-56-3 ] Synthesis Path-Downstream 1~33

1
[ 1121-78-4 ]
[ 158690-56-3 ]
[ 914086-49-0 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate; In N,N-dimethyl-formamide; at 100℃; for 2h;	(Reference Example 7) Synthesis of 2-((6-methylpyridin-3-yl)oxy)ethylamine dihydrochloride To a solution of tert-butyl N-(2-hydroxyethyl)carbamate (49.9 g, 310 mmol) and 4-dimethylaminopyridine (42 g, 340 mmol) in dichloromethane (500 mL) was slowly added tosyl chloride (59 g, 310 mmol) under ice-cooling. The mixture was allowed to cool to room temperature, stirred for 15 hr, washed with water and saturated brine, and concentrated to give 2-((tert-butoxycarbonyl)amino)ethyl 4-methyl benzenesulfonate (98 g). 66 g (209 mmol) of these was dissolved in DMF (500 mL), 5-hydroxy-2-methylpyridine (22.8 g, 209 mmol) and cesium carbonate (102 g, 314 mmol) were added, and the mixture was stirred at 100C for 2 hr. The reaction mixture was allowed to cool to room temperature, poured into cool water, and extracted with ethyl acetate three times. The organic layer was washed with saturated brine, and concentrated to give crystals (35 g). The crystals were washed with tert-butyl-methyl ether to give tert-butyl (2-((6-methylpyridin-3-yl)oxy)ethyl)carbamate (24.5 g) as white crystals. The crystals were treated with 2N-HCl/Dioxane solution (140 ml) at room temperature, and the obtained insoluble substance was collected by filtration to give the object compound of 2-((6-methylpyridin-3-yl)oxy)ethylamine dihydrochloride (17.6 g). 1H-NMR(300MHz, DMSO-d6)δ(ppm) : 8.49(d,1H), 8.42(br-s,2H), 8.05(dd,1H), 7.78(d,1H), 4.40(t,2H)3.23-3.13(m,2H)

References: [1]Patent: EP1876178,2008,A1 .Location in patent: Page/Page column 9-10.

2
[ 47491-38-3 ]
[ 158690-56-3 ]
[ 955359-90-7 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; sodium iodide; In acetone; at 66℃;Heating / reflux;	Intermediate 191 ,1 -Dimethylethyl (2-{4-[4-[(4-chlorophenyl)methyl]-1 -oxo-2(1 H)-phthalazinyl] hexahydro-1H-azepin-1-yl}ethyl)carbamateA solution of 4-[(4-chlorophenyl)methyl]-2-(hexahydro-1H-azepin-4-yl)-1 (2/-/)- phthalazinone (for example, as prepared for Intermediate 16) (0.16 g, 0.43 mmol) in acetone (5 ml) was treated with a solution of 2-([(1 ,1- dimethylethyl)oxy]carbonyl}amino)ethyl 4-methylbenzenesulfonate (for example, as disclosed in LE. Canne, R.L. Winston, S.B.H. Kent, Tet. Lett., 38:3361-4, (1997), see <n="70"/>compound 2) (0.15 g, 0.47 mmol) in acetone (2 ml), followed by sodium iodide (64.7 mg, 0.43 mmol) and DIPEA (51.8 μl, 0.43 mmol) and the mixture was heated to 66 0C under nitrogen overnight. The following morning another portion of 2-([(1 ,1- dimethylethyl)oxy]carbonyl}amino)ethyl 4-methylbenzenesulfonate (75 mg) and DIPEA (26 μl) were added and the mixture heated for another day. The mixture was then applied to an SCX-2 cartridge (20 g), washed with MeOH and eluted with 10% aq. ammonia in MeOH. The ammoniacal fractions were concentrated under reduced pressure and the residue was purified by chromatography (Flashmaster II, 50 g cartridge) eluting with 0 to 30% MeOH containing 1 % NEt3 - DCM over 30 min to give the title compound (133.8 mg). LCMS RT = 2.80 min, ES+ve m/z 51 1 (M+H)+.

References: [1]Patent: WO2007/122156,2007,A1 .Location in patent: Page/Page column 68-69.

3
[ 24424-99-5 ]
[ 158690-56-3 ]

References: [1]Journal of labelled compounds and radiopharmaceuticals,2002,vol. 45,p. 115 - 137.
[2]Patent: US2008/153802,2008,A1 .
[3]Patent: WO2017/64628,2017,A1 .
[4]Patent: US2018/111897,2018,A1 .
[5]Organic Letters,2019,vol. 21,p. 3891 - 3894.

4
[ 24424-99-5 ]
pentacarbonyl<1-<<(1R,2S,5R)-5-methyl-2-(1-methyl-1-phenylethyl)cyclohexyl>oxy>-(E)-3-phenyl-2-propenylidene>chromium [ No CAS ]
[ 158690-56-3 ]

References: [1]Journal of labelled compounds and radiopharmaceuticals,1998,vol. 41,p. 491 - 502.

5
[ 158690-56-3 ]
[ 142604-13-5 ]

References: [1]Tetrahedron Letters,1997,vol. 38,p. 3361 - 3364.
[2]Patent: US2015/31674,2015,A1 .

6
[ 158690-56-3 ]
2-<<(N-t-Boc)-2-aminoethyl>sulphonyl>ethyl p-nitrophenyl carbonate [ No CAS ]

References: [1]Tetrahedron Letters,1997,vol. 38,p. 3361 - 3364.

7
[ 178814-33-0 ]
[ 158690-56-3 ]
[ 752253-15-9 ]

Yield	Reaction Conditions	Operation in experiment
32%	With sodium hydroxide; tetra(n-butyl)ammonium hydrogensulfate; In water; toluene; at 20℃; for 12h;	Zu einer Mischung aus 50. 0 G (91.4 MMOL) 1,3, 5-TOD-2, 4,6- TRISHYDROXYMETHYLBENZEN, und 3 G (8.7 MMOL) Tetrabutylammoniumhydrogensulfat in 200 mi 32proz. NaOH-L?sung und 300 ML Toluol werden bei Raumtemp. 142 G (450 mmol) Toluolsulfons?ure-2- TERT-BUTOXYCARBONYLAMINOETHYLESTER (Canne et AL., Tetrahedron Letters, 38, 1997,3361) gel?st in 250 ML Toluol zugetropft und anschlie?end 12 h gerührt. Es wird mit 300 M . WASSER versetzt und zweimal mit je 300 mi Toluol extrahiert. Die vereinigten organischen Phasen werden über Natriumsulfat getrocknet, das L?sungsmittel zur Trockene eingeengt und an Kieselgel chromatographiert (Laufmittel HEXAN/ETHYLACETAT 10 : 1). Die das Produkt enthaltenden Fraktionen werden vereinigt und eingedampft. Ausbeute 28.6 G (32 % d. Th. ) eines farblosen Feststoffes Elementaranalyse : ber. : C 36.94 H 4.96 N 4. 31 137. 75 gef. : C 36.98 H 4.90 N 4. 27 1 37. 64
32%	With sodium hydroxide; tetra(n-butyl)ammonium hydrogensulfate; In toluene; at 20℃; for 12h;	142 g (450 mmol) of toluenesulfonic acid-2-tert-butoxycarbonylaminoethyl ester (Canne et al., Tetrahedron Letters, 38, 1997, 3361), dissolved in 250 ml of toluene, is added in drops to a mixture that consists of 50.0 g (91.4 mmol) of 1,3,5-triiodo-2,4,6-trishydroxymethylbenzene, and 3 g (8.7 mmol) of tetrabutylammonium hydrogen sulfate in 200 ml of 32% NaOH solution and 300 ml of toluene at room temperature, and then it is stirred for 12 hours. It is mixed with water and extracted twice with 300 ml each of toluene. The combined organic phases are dried on sodium sulfate, the solvent is evaporated to the dry state and chromatographed on silica gel (mobile solvent:hexane/ethyl acetate 10: 1). The fractions that contain the product are combined and concentrated by evaporation. [0366] Yield: 28.6 g (32% of theory) of a colorless solid [0367] Elementary analysis: Cld.: C, 36.94; H, 4.96; N, 4.31; I, 37.75. Fnd.: C, 36.98; H, 4.90; N, 4.27; I, 37.64.

References: [1]Patent: WO2004/74267,2004,A1 .Location in patent: Page 63.
[2]Patent: US2004/265236,2004,A1 .Location in patent: Page/Page column 21.

8
[ 872373-76-7 ]
[ 158690-56-3 ]
[ 872373-81-4 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate; In DMF (N,N-dimethyl-formamide); at 80℃; for 19h;	To a solution of crude 19 (105 mg) in DMF (3.0 ml) were added Cs2C03 (654 mg, 2.00 mmol) and tert-butyl N- (2-tosyloxyethyl)-carbamate mg, 1.67 mmol), and heated to 80 C under nitrogen. After stirring for 4 h, additional Cs2C03 (654 mg, 2.00 mmol) and tert-butyl N- (2-tosyloxyethyl)-carbamate mg, 1.67 mmol) were added. After stirring further 15 h, the reaction mixture was taken into AcOEt and IN HCI. The organic layer was washed with IN HCl x2, water and brine, dried over Na2S04. The solvent was removed under vacuum and purified by preparative TLC (CHCl3/MeOH = 10/1) to afford 20, which was dissolved in DMF (2 ml) and acetic anhydride (0.5 ml) was added. After stirring at 80 C for 1 h, the mixture was diluted with AcOEt and washed with water x3, saturated Na2C03, brine, dried over Na2S04. The solvent was removed under vacuum and purified by preparative TLC (AcOEt/hexane = 1/1) to afford 21 (38 mg, 16 % yield from 18).

References: [1]Patent: WO2005/123676,2005,A1 .Location in patent: Page/Page column 41; 44.

9
[ 100-53-8 ]
[ 158690-56-3 ]
[ 873330-01-9 ]

Yield	Reaction Conditions	Operation in experiment
83%	With caesium carbonate; In N,N-dimethyl-formamide; for 18h;	67C: N-Boc-2-Benzylsulfanyl-ethylamine; N-Boc-2-Tosyl-ethylamine (100 mg, 0.32 mmol) was added to a mixture of benzylmercaptan (45 mL, 0.38 mmol) and CsaCOs (68 mg, 0.21 mmol) in 1.6 mL of dry DMF. The reaction was stirred for 18 hours after which time the reaction mixture was poured onto water. The aqueous layer was extracted three times with AcOEt. The combined organic layers were washed with water, saturated NaHCOs and brine, dried over Na2SC>4 and concentrated. The residue was purified using SiC>2 with AcOEt/Petroleum ether 5:95 to 15:75. A yellow oil was obtained (72 mg, 83%). NMR 'H (ppm, CDC13): 7.31-7.25 (m, 5H), 4.79 (br. s., 1H), 3.70 (s, 2H), 3.25 (m, 2H), 2.55-2.53 (m, 2H), 1.43 (s, 9H).
83%	With caesium carbonate; In N,N-dimethyl-formamide; for 18h;	67C: N-Boc-2-Benzylsulfanyl-ethylamine; N-Boc-2-Tosyl-ethylamine (100 mg, 0.32 mmol) was added to a mixture of benzylmercaptan (45 mL, 0.38 mmol) and Cs2CO3 (68 mg, 0.21 mmol) in 1.6 mL of dry DMF. The reaction was stirred for 18 hours after which time the reaction mixture was poured onto water. The aqueous layer was extracted three times with AcOEt. The combined organic layers were washed with water, saturated NaHCO3 and brine, dried over Na2SO4 and concentrated. The residue was purified using SiO2 with AcOEt/Petroleum ether 5:95 to 15:75. A yellow oil was obtained (72 mg, 83%). NMR 1H (ppm, CDCl3): 7.31-7.25 (m, 5H), 4.79 (br. s., 1H), 3.70 (s, 2H), 3.25 (m, 2H), 2.55-2.53 (m, 2H), 1.43 (s, 9H).

References: [1]Patent: WO2006/2474,2006,A1 .Location in patent: Page/Page column 174.
[2]Patent: US2008/153802,2008,A1 .Location in patent: Page/Page column 86-87.

10
[ 16732-80-2 ]
[ 158690-56-3 ]
ethyl 1-(2-tert-butoxycarbonylaminoethyl)-4-methyl-1H-indole-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In N,N-dimethyl-formamide;	c) Synthesis of ethyl 1-(2-tert-butoxycarbonylaminoethyl)-4-methyl-1H-indole-2-carboxylate A mixture of <strong>[16732-80-2]ethyl 4-methyl-1H-indole-2-carboxylate</strong> (42.9 g, 211 mmol), 60% sodium hydride (9.29 g, 232 mmol) and N,N-dimethylformamide (300 ml) was stirred at room temperature for 1 hour. A solution of 2-tert-butoxycarbonylaminoethyl 4-toluenesulfonate (86.6 g, 275 mmol) in N,N-dimethylformamide (200 ml) was added dropwise and the resulting mixture was stirred at room temperature for 9 hours. The reaction mixture was poured into ice water and extracted twice with ethyl acetate, and the extract solution was washed with a 5% aqueous sodium chloride solution and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and the resulting residue was purified by a silica gel column chromatography (eluent:ethyl acetate/n-hexobtain 2 3/97) to obtain 24.4 g of ethyl 1-(2-tert-butoxycarbonylaminoethyl)-4-methyl-1H-indole-2-carboxylate. M.p. 93-94 C. (after recrystallization from isopropanol).

References: [1]Patent: US5834454,1998,A .

11
[ 34137-14-9 ]
[ 158690-56-3 ]
[ 942998-95-0 ]

Yield	Reaction Conditions	Operation in experiment
86%	With caesium carbonate; In N,N-dimethyl-formamide; at 50℃;	Methyl 4-(2-(tert-butyloxycarbonylamino)ethoxy-3,5 -dimethylbenzoate. A stirred solution of methyl 4-hydroxy-3,5-dimethylbenzoate (8.65 g, 48.06 mmol) and caesium carbonate (23.5 g, 72.08 mmol) in N,N-dimethylformamide (50 ml) at 50 C was treated with N- (tert-butyloxycarbonyl)-O-(4-methylphenylsulphonyl)-ethanolamine (23.0 g, 0.73 mmol) in small portions over a period of 8 h. The mixture was stirred at 50 C overnight and the solvent removed in vacuo. The residues were partitioned between 2 M sodium hydroxide and dichloromethane, the organic layer separated and evaporated to dryness in vacuo to afford the crude product as a brown oil. Purification by column chromatography on silica eluting with 5-20% ethyl acetate in petroleum ether afforded the product as a colorless solid (13.4 g, 86%). 1H NMR (DMSOd6) 7.65 (2H, s), 7.09 (IH, t), 3.82 (3H, s), 3.78 (2H, m), 3.30 (2H, m), 2.26 (6H, s), 1.40 (9H, s). LC/MS: (PS-A2) Rt 3.38 [M+H]+ 324.

References: [1]Patent: WO2007/72041,2007,A1 .Location in patent: Page/Page column 59.
[2]Journal of Medicinal Chemistry,2008,vol. 51,p. 183 - 186.

12
[ 288-32-4 ]
[ 158690-56-3 ]
[ 558441-67-1 ]

Yield	Reaction Conditions	Operation in experiment
29%		[0199] Tosyl chloride (1.50 g, 7.87 mmol) was added to a solution of (2-hydroxy-ethyl)-carbamic acid tert-butyl ester (0.84 g, 5.2 mmol) and Et3N (1.23 mL, 8.82 mmol) in CH2Cl2 (26 mL), and the solution was stirred at room temperature for 17 h. The solution was washed with H2O (15 mL), and the aqueous phase was extracted with CH2Cl2 (10 mL). The combined organic phases were dried (MgSO4) and concentrated in vacuo. Purification of the crude material by column chromatography on silica gel (20% EtOAc/hexanes) gave yellow crystals (1.29 g, 79%). 1H NMR (CDCl3) δ 1.41 (s, 9H), 2.45 (s, 3H), 3.38 (m, 2H), 4.07 (m, 2H), 4.82 (br s, 1H), 7.35 (d, 2H, J=8.1 Hz), 7.79 (d, 2H, J=8.1 Hz). [0200] (2-Imidazol-1-yl-ethyl)-carbamic Acid Tert-Butyl Ester. [CHEMMOL-00028] [0201] A solution of imidazole (253 mg, 3.72 mmol) in DMF (2 mL) was added to a suspension of NaH (60% in mineral oil, 164 mg, 4.10 mmol) in DMF (8 mL), and the mixture was stirred at room temperature for 45 minutes. A solution of <strong>[158690-56-3]toluene-4-sulfonic acid 2-tert-butoxycarbonylamino-ethyl ester</strong> (1.29 g, 4.09 mmol) in DMF (6 mL) was added, and the mixture was stirred at room temperature for 16 h then concentrated in vacuo. The residue was partitioned between H2O (25 mL) and EtOAc (25 mL), and the aqueous phase was extracted with EtOAc (25 mL). The combined organic phases were dried (MgSO4) and concentrated in vacuo. Purification of the crude material by column chromatography on silica gel (200:5:1-100:5:1 CH2Cl2/MeOH/NH4OH) gave a colourless oil (224 mg, 29%). 1H NMR (CDCl3) δ 1.44 (s, 9H), 3.43 (m, 2H), 4.08 (m, 2H), 4.64 (br s, 1H), 6.92 (s, 1H), 7.09 (s, 11H), 7.46 (s, 1H). [0202] (2-Imidazol-1-yl-ethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amine. [CHEMMOL-00029] [0203] A solution of (2-imidazol-1-yl-ethyl)-carbamic acid tert-butyl ester (224 mg, 1.06 mmol) in 1:1 TFA/CH2Cl2 (4 mL) was stirred at room temperature for 1 h then concentrated in vacuo. The residue was dissolved in 1 N NaOH(aq) (10 mL) then saturated with sodium chloride and extracted with CHCl3 (5×15 mL). The combined organic extracts were dried (MgSO4) and concentrated in vacuo to give a yellow oil (55 mg). [0204] Using General Procedure B: To a stirred solution of the amine from above (55 mg), 6,7-dihydro-5H-quinolin-8-one (73 mg, 0.50 mmol), and AcOH (0.030 mL, 0.52 mmol) in THF (5 mL) was added NaBH(OAc)3 (315 mg, 1.49 mmol) and the mixture was stirred at room temperature for 2 h. The crude material was dissolved in saturated HBr/AcOH (2 mL) and stirred at room temperature for 15 minutes. The solution was made basic with 10 N NaOH(aq) and extracted with CH2Cl2 (3×15 mL). The combined organic extracts were dried (MgSO4) and concentrated in vacuo. Purification of the crude material by column chromatography on silica gel (200:5:1 CH2Cl21MeOH/NH4OH) gave a yellow oil (92 mg, 77%). 1H NMR (CDCl3) δ 1.73 (m, 2H), 1.91-2.13 (m, 2H), 2.76 (m, 2H), 3.12 (m, 2H), 3.78 (m, 1H), 4.11 (m, 2H), 7.01 (s, 1H), 7.08 (m, 2H), 7.38 (d, 1H, J=7.5 Hz), 7.56 (s, 1H), 8.37 (d, 1H, J=3.9 Hz). [0205] 2-[(2-Imidazol-1-yl-ethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzimidazole-1-carboxylic Acid Tert-Butyl Ester. [CHEMMOL-00030] [0206] A mixture of (2-imidazol-1-yl-ethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amine (92 mg, 0.37 mmol), 2-chloromethyl-benzimidazole-1-carboxylic acid tert-butyl ester (101 mg, 0.379 mmol), potassium iodide (3 mg, 0.02 mmol), and N,N-diisopropylethylamine (0.10 mL, 0.57 mmol) in acetonitrile (4 mL) was heated at 60 C. for 15 h. Saturated NaHCO3 (aq) (15 mL) was added, and the mixture was extracted with CH2Cl2 (3×15 mL). The combined organic extracts were dried (MgSO4) and concentrated in vacuo. Purification of the crude material by column chromatography on silica gel (250:5:1 CH2Cl2/MeOH/NH4OH) gave a yellow oil (21 mg, 12%). 1H NMR (CDCl3) δ 1.45 (m, 1H), 1.66 (m, 10H), 1.91 (m, 2H), 2.69 (m, 2H), 2.92 (m, 1H), 3.18 (m, 1H), 3.67 (m, 2H), 4.20 (dd, 1H, J=10, 5.6 Hz), 4.67 (d, 1H, J=15 Hz), 4.80 (d, 1H, J=15 Hz), 6.74 (s, 1H), 6.90 (s, 1H), 7.01 (dd, 1H, J=7.7, 4.7 Hz), 7.33 (m, 4H), 7.73 (m, 1H), 7.86 (m, 1H), 8.38 (d, 1H, J=3.3 Hz). [0207] (1H-Benzimidazol-2-ylmethyl)-(2-imidazol-1-yl-ethyl)-(5,6,78-tetrahydro-quinolin-8-yl)-amine (COMPOUND 12). [0208] A solution of 2-[(2-imidazol-1-yl-ethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzimidazole-1-carboxylic acid tert-butyl ester (21 mg, 0.044 mmol) in 3:1 TFA/CH2Cl2 (4 mL) was stirred at room temperature for 30 minutes then concentrated in vacuo. The residue was partitioned between CH2Cl2 (20 mL) and 1 N NaOH(aq) (10 mL), and the aqueous phase was extracted with CH2Cl2 (10 mL). The combined organic extracts were dried (MgSO4) and concentrated in vacuo to afford COMPOUND 12 as a yellow foam (15 mg, 83%). 1H NMR (CDCl3) δ 1.73 (m, 2H), 1.99 (m, 1H), 2.20 (m, 1H), 2.69-2.88 (m, 2H), 2.92-3.08 (m, 2H), 3.82-3.98 (m, 2H), 4.04 (d, 1H, J=17 Hz), 4.09 (m, 1H), 4.19 (d, 1H, J=17 Hz), 6.70 (s, 1H), 6.93 (s, 1H), 7.18 (m, 3H...
29%	With NaH; In N,N-dimethyl-formamide; mineral oil;	(2-Imidazol-1-yl-ethyl)-carbamic acid tert-butyl Ester. A solution of imidazole (253 mg, 3.72 mmol) in DMF (2 mL) was added to a suspension of NaH (60% in mineral oil, 164 mg, 4.10 mmol) in DMF (8 mL), and the mixture was stirred at room temperature for 45 minutes. A solution of <strong>[158690-56-3]toluene-4-sulfonic acid 2-tert-butoxycarbonylamino-ethyl ester</strong> (1.29 g, 4.09 mmol) in DMF (6 mL) was added, and the mixture was stirred at room temperature for 16 h then concentrated in vacuo. The residue was partitioned between H2O (25 mL) and EtOAc (25 mL), and the aqueous phase was extracted with EtOAc (25 mL). The combined organic phases were dried (MgSO4) and concentrated in vacuo. Purification of the crude material by column chromatography on silica gel (200:5:1-100:5:1 CH2Cl2/MeOH/NH4OH) gave a colourless oil (224 mg, 29%). 1H NMR (CDCl3) δ 1.44 (s, 9H), 3.43 (m, 2H), 4.08 (m, 2H), 4.64 (br s, 1H), 6.92 (s, 1H), 7.09 (s, 1H), 7.46 (s, 1H).

References: [1]Patent: US2003/220341,2003,A1 .Location in patent: Page/Page column 17-19.
[2]Patent: US2004/19058,2004,A1 .

13
[ 591-27-5 ]
[ 158690-56-3 ]
[ 246240-10-8 ]

Yield	Reaction Conditions	Operation in experiment
58%	With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; for 15h;Inert atmosphere;	Step 1: A mixture of 1-aminophenol (1) (207 mg, 1.9 mmol), 2-(fert-butoxycarbonylamino)ethyl 4- methylbenzenesulfonate (2) (500 mg, 1.9 mmol), and cesium carbonate (770 mg, 2.2 mmol) in DMF (6 ml) was stirred at room temperature under argon for 15 hours. The mixture was concentrated under reduced pressure. The residue was partitioned between EtOAc and water. The organic layer was washed with brine, dried over Na2SO4 and concentrated under reduced pressure. Purification by flash chromatography (40 to 60% EtOAc -hexanes gradient) gave tert-buty 2-(3- aminophenoxy)ethylcarbamate (3) as colorless oil. Yield (220 mg, 58%). 1H NMR (400 MHz, DMSO-J6) δ 6.92 (t, J = 5.2 Hz, IH), 6.85 (t, J = 8.0 Hz, IH), 6.08-6.12 (m, 2H), 6.02-6.04 (m, IH), 4.99 (bs, 2H), 3.79 (t, J= 6.0 Hz, 2H), 3.21 (q, J= 6.0 Hz, 2H), 1.36 (s, 9H).

References: [1]Patent: WO2010/48332,2010,A2 .Location in patent: Page/Page column 155.

14
[ 158690-56-3 ]
[ 117861-38-8 ]

References: [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 8588 - 8602.
[2]Heterocycles,2009,vol. 77,p. 865 - 872.

15
[ 1240325-36-3 ]
[ 158690-56-3 ]
C₃₉H₄₂N₂O₆ [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 5956 - 5969.

16
[ 518-47-8 ]
[ 158690-56-3 ]
fluorescein-di-O,O'-N-Boc-ethylamine [ No CAS ]

References: [1]Organic and Biomolecular Chemistry,2012,vol. 10,p. 3379 - 3383.

17
[ 158690-56-3 ]
fluorescein-O'-N-Boc-ethylamine [ No CAS ]

References: [1]Organic and Biomolecular Chemistry,2012,vol. 10,p. 3379 - 3383.

18
[ 158690-56-3 ]
[ 1394248-15-7 ]