62058-03-1|Rel-(1R,3S,4R)-4-aminoadamantan-1-ol| Ambeed

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Quality Control of [ 62058-03-1 ] Purity: 95% SDS Specification

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Product Details of [ 62058-03-1 ]

CAS No. :	62058-03-1
Formula :	C₁₀H₁₇NO
M.W :	167.25
SMILES Code :	O[C@]12C[C@@]3([H])[C@H](N)C(C2)CC(C3)C1
MDL No. :	MFCD12761603

Safety of [ 62058-03-1 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H332-H335
Precautionary Statements:	P261-P280-P305+P351+P338

Computational Chemistry of [ 62058-03-1 ] Show Less

Physicochemical Properties

Num. heavy atoms	12
Num. arom. heavy atoms	0
Fraction Csp3	1.0
Num. rotatable bonds	0
Num. H-bond acceptors	2.0
Num. H-bond donors	2.0
Molar Refractivity	47.75
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	46.25 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.8
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	0.43
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	0.88
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.	1.52
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	0.95
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.12

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-1.15
Solubility	11.9 mg/ml ; 0.0711 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-0.97
Solubility	18.0 mg/ml ; 0.107 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very 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	-0.77
Solubility	28.1 mg/ml ; 0.168 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	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	No
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	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.	-7.01 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	0.0 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)	3.77

Application In Synthesis of [ 62058-03-1 ]

* 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.

Downstream synthetic route of [ 62058-03-1 ]

[ 62058-03-1 ] Synthesis Path-Downstream 1~35

1
2-adamantylammonium para-chlorobenzenesulfonate [ No CAS ]
(1 s,3R,4r,5S,7s)-4-aminoadamantan-1-ol [ No CAS ]
[ 62058-03-1 ]

References: [1]Organic Letters,2000,vol. 2,p. 831 - 834.

2
[ 332-77-4 ]
[ 62058-03-1 ]
C₁₄H₁₉NO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; In water; at 20℃;	A mixture of 2,5-dihydro-2,5-dimethoxy- furan (0.01 mol) and 4-amino-, (la,3a,4a,5i,7a)- tricyclo[3.3.1. 13,7]decan-l-ol (0.01 mol) in water (50 ml) was stirred at room temperature. Hydrochloric acid concentrated (2 ml) was added and the reaction mixture was stirred overnight. The acidic mixture was neutralized with an aqueous NaHC03 solution. This mixture was extracted with DCM (3 x). The combined organic layers were dried, filtered and the solvent evaporated, yielding 1.5 g of intermediate 13.

References: [1]Patent: WO2005/108361,2005,A1 .Location in patent: Page/Page column 19.

3
[ 20769-85-1 ]
(1 s,3R,4r,5S,7s)-4-aminoadamantan-1-ol [ No CAS ]
[ 62058-03-1 ]
E-2-bromo-N-(5-hydroxy-adamantyl-2-yl)-2-methyl-propionamide [ No CAS ]
Z-2-bromo-N-(5-hydroxy-adamantyl-2-yl)-2-methyl-propionamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0 - 20℃; for 2h;	Example IB E-2-bromo-N-r5-hvdroxy-adamantan-2-ylV2-methyl-propionamide; A solution of E- and Z-5-hydroxy-2-adamantamine (0.868g, 5.2 mmoles) in DCM (15.0 mL) and DIPEpsilonA (2.5 mL) was cooled in an ice bath and treated with 2-bromoisobutyryl bromide (0.72 mL, 5.8 mmoles) in DCM (2.5 mL). The mixture was stirred for 2 hours at room temperature and DCM was removed under reduced pressure. The residue was partitioned between water and ethyl acetate. The organic layer was washed with saturated sodium bicarbonate, water, dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure to provide the title compound as dark beige solid (1.17 g, 71percent). The isomers were separated by column chromatography (silica gel, 5-35percent acetone in hexane) to furnish 0.78 g of E-2-bromo-N-(5-hydroxy-adamantan-2-yl)-2-methyl-propionamide and 0.39 g of Z-2-bromo-N-(5-hydroxy-adamantan-2-yl)-2-methyl-propionamide.Example 1C

References: [1]Patent: WO2006/74244,2006,A2 .Location in patent: Page/Page column 51.

4
[ 937746-45-7 ]
[ 62058-03-1 ]
C₂₈H₄₃N₃O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In N,N-dimethyl-formamide; at 20℃; for 24h;	To a solution of Compound 21(181mg) in dimethyl formamide were added hydroxy adamantanamine(94mg), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride(118mg), 1-hydroxybenzotriazole(21mg) and triethylamine(121mul), then the resulting solution was stirred at room temperature for 24hrs. After termination of the reaction, the solution was diluted with 2N HCl aqueous soln. and extracted with ethyl acetate. The organic layer was washed with sat. sodium hydrogencarbonate soln. and brine successively, and dried with magnesium sulfate. The residue was purified by silicagel columnchromatography to give Compound 22(176mg).

References: [1]Patent: EP1953145,2008,A1 .Location in patent: Page/Page column 36-37.

5
[ 937746-51-5 ]
[ 62058-03-1 ]
C₂₅H₃₈N₄O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 20℃; for 13h;	To a solution of Compound 29(102mg) in methylene chloride(2ml) were added hydroxy adamantanamine(81mg), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride(82mg), 1-hydroxybenzotriazole(14mg) and triethylamine(115mul), then the resulting solution was stirred at room temperature for 13hrs. After termination of the reaction, the solution was acidified with 2N HCl aqueous soln. and extracted with methylene chloride. The organic layer was washed with sat. sodium hydrogencarbonate soln. and brine successively, and dried with sodium sulfate. The residue was purified by silicagel columnchromatography to afford Compound C-202(123mg).

References: [1]Patent: EP1953145,2008,A1 .Location in patent: Page/Page column 38.

6
[ 937746-53-7 ]
[ 62058-03-1 ]
C₂₄H₃₇N₅O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In N,N-dimethyl-formamide; at 20℃; for 18h;	To a solution of Compound 32(193mg) in dimethyl formamide(4ml) were added hydroxy adamantanamine(152mg), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride(155mg), 1-hydroxybenzotriazole(26mg) and triethylamine(217mul), then the resulting solution was stirred at room temperature for 18hrs. After termination of the reaction, the solution was acidified with 2N HCl aqueous soln. and extracted with methylene chloride. The organic layer was washed with sat. sodium hydrogencarbonate soln. and brine successively, and dried with sodium sulfate. The residue was purified by silicagel columnchromatography to give Compound C-186(36mg).

References: [1]Patent: EP1953145,2008,A1 .Location in patent: Page/Page column 39.

7
C₁₂H₂₀N₂O₅S [ No CAS ]
[ 62058-03-1 ]
C₂₂H₃₅N₃O₅S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane;	Example 37; [Show Image] According to the above scheme, Compound C-159 was synthesized.

References: [1]Patent: EP1953145,2008,A1 .Location in patent: Page/Page column 42-43.

8
[ 1023272-73-2 ]
[ 62058-03-1 ]
C₁₉H₂₉N₃O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In N,N-dimethyl-formamide; at 20℃; for 14h;	Example 8; [Show Image] To a dimethylformamide solution (DMF) (5 ml) of a compound V-1 (150 mg) were added monohydroxy-2-adamantamine (140 mg), 1-hydroxybenzotriazole (HOBT) (31 mg), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (WSC) (174 mg), and triethylamine (TEA) (180 mul) under the nitrogen atmosphere, and the mixture was stirred at room temperature for 14 hours. After completion of the reaction, 2N hydrochloric acid (30 ml) was added thereto followed by extraction with ethyl acetate. The organic layer was washed successively with aqueous saturated sodium hydrogen carbonate solution and saturated brine, and dried with magnesium sulfate. A solvent was evaporated, and the residue was purified by silica gel chromatography to obtain a compound VI-1 (226 mg). 1H NMR: (CDCl3); d 1.06 (d, J = 6.6 Hz, 6H), 1.53 - 2.20 (m, 14H), 3.72 (s, 3H), 3.98 (d, J = 6.6 Hz, 2H), 6.25 - 6.30 (m, 1H), 7.71 (s, 1H).(Reference Example 1) The mother washed liquid at filtration obtained in Example 2 was concentrated under reduced pressure, the solvent was evaporated, thereafter, silica gel chromatography (chloroform : methanol = 100 : 0 to 94 : 6) was performed, and fraction solutions corresponding to the formula (III-1'):

References: [1]Patent: EP2088136,2009,A1 .Location in patent: Page/Page column 24-25.

9
C₁₇H₂₃NO [ No CAS ]
[ 62058-03-1 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogen;palladium on activated charcoal; In tetrahydrofuran; for 2.5h;	Example 3; [Show Image] [Show Image] A compound III-1 (150 mg) was dissolved in tetrahydrofuran (3 ml), 10percent palladium carbon (30 mg) was added thereto, and hydrogen gas was introduced therein for 2.5 hours. After the catalyst was filtered, the filtrate was evaporated under reduced pressure to obtain the residue of a compound IV (100 mg, crude yield = 102.6percent). Compound (IV) 1H NMR (300 MHz, d6-DMSO): d 1.17 - 1.95 (m, 11H), 2.50 (m, 2H), 2.84 (brs, 1H). 13C NMR (75.4 MHz, CDCl3): d 29.3 (2C), 30.0 (1C), 36.8 (2C), 44.8 (2C), 45.6 (1C), 54.3 (1C), 67.5 (1C).

References: [1]Patent: EP2088136,2009,A1 .Location in patent: Page/Page column 21-22.

10
[ 13074-39-0 ]
(1 s,3R,4r,5S,7s)-4-aminoadamantan-1-ol [ No CAS ]
[ 62058-03-1 ]

References: [1]Russian Journal of Organic Chemistry,2009,vol. 45,p. 1137 - 1142.

11
[ 17413-73-9 ]
[ 62058-03-1 ]
2-(3-chloro-phenoxy)-<i>N</i>-(5-hydroxy-adamantan-2-yl)-2-methyl-propionamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Example B.18 a) Preparation of compound 43; To a mixture of 2-(3-chlorophenoxy)-2-methyl-propanoic acid [17413-73-9] (0.010 mol) and CH2Cl2 (70 ml), HOBt (0.012 mol) was added at room temperature. The mixture was stirred until complete dissolution of HOBt. EDCI (0.012 mol) was added and the mixture was stirred at room temperature for 30 minutes. (lalpha,3alpha,4alpha,5beta,7alpha)- 4-aminotricyclo[3.3.1.13'7]decan-l-ol [62058-03-1] (0.012 mol) was added and the mixture was stirred at room temperature overnight. The solvent was evaporated. The residue was dissolved in CH2CI2 and washed with 15percent citric acid solution, IM Na2CO3 and water. The organic layer was separated, dried (MgSO4), filtered and the solvent was evaporated. The residue was purified by column chromatography (eluent: CH2C12/CH3OH 100/0 to 98/2). Two product fraction groups were collected and the solvents were evaporated. The residue was crystallized from DIPE. The precipitate was filtered off and dried, yielding 1.97g of compound 43.

References: [1]Patent: WO2006/24627,2006,A2 .Location in patent: Page/Page column 51-52; 60.

12
[ 62058-03-1 ]
[ 212578-38-6 ]
C₂₀H₂₆N₂O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Example B .5 Preparation of compound 6; iV-(ethylcarbonimidoyl)-iV,iV-dimethyl-l,3-propanediamine, monohydrochloride [25952-53-8] (0.0022 mol) and 1 -hydroxy- lH-benzotriazole (0.0022 mol) were added to a solution of intermediate 6 [212578-38-6] (0.002 mol) in DMF (25 ml) and the mixture was stirred and warmed (40°C). Then a solution of 4-amino- (lalpha,3alpha,4alpha,5beta,7alpha) tricyclo[3.3.1.13'7]decan-l-ol [62058-03-1] (0.0024 mol) in hot DMF was added and the reaction mixture was stirred overnight at room temperature. The mixture was poured out into ice-water and was extracted with EtOAc. The obtained extract was washed with water and with brine and then dried and concentrated, yielding 0.040 g of compound 6. Example B .6

References: [1]Patent: WO2006/24627,2006,A2 .Location in patent: Page/Page column 45; 55.

13
[ 28361-38-8 ]
[ 62058-03-1 ]
C₂₀H₂₆ClNO₄S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Example B .3 Preparation of compound 3; A mixture of 2-[(p-chlorophenyl)sulfonyl]-2-methylpropionic acid [28361-38-8] (0.00028 mol) in dichloromethane (5 ml) and DMF (5 ml) was stirred and 1-hydroxy- lH-benzotriazole (O.OOO33 mol) was added. Then the mixture was stirred for 10 minutes and iV-(ethylcarbonimidoyl)-iV,iV-dimethyl-l,3-propanediamine, monohydrochloride [25952-53-8] (O.OOO33 mol) was added. The resulting mixture was stirred for 10 minutes and (lalpha,3alpha,4alpha,5beta,7alpha) -4-aminotricyclo[3.3.1.13'7]decan-l-ol [62058-03-1] (O.OOO33 mol) was added. The reaction mixture was stirred overnight at room temperature and then the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2CyCH3OH 98/2). The product fractions were collected and the solvent was evaporated, yielding 0.094 g of compound 3.

References: [1]Patent: WO2006/24627,2006,A2 .Location in patent: Page/Page column 44; 56.

14
[ 24673-56-1 ]
[ 62058-03-1 ]
C₂₀H₂₃NO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Example B .6 Preparation of compound 7; 1 -Hydroxy- lH-benzotriazo Ie (0.001 mol) was added to a stirred mixture of 3-methylbenzofurancarboxylic acid [24673-56-1] (0.0009 mol) in dichloromethane (5 ml) and DMF (5 ml). The mixture was stirred for 10 minutes and iV-(ethyl- carbonimidoyl)-iV,iV-dimethyl-l,3-propanediamine, monohydrochloride [25952-53-8] (0.001 mol) was added. The resulting mixture was stirred for 1 hour before (lalpha,3alpha,4alpha,5beta,7alpha)-4-aminotricyclo[3.3.1.13'7]decan-l-ol [62058-03-1] (0.001 mol) was added. The reaction mixture was stirred at room temperature overnight and then (Polystyrylmethyl)-trimethylammonium bicarbonate (I g; Novabiochem Cat. No.: 01-64-0419) and Methylisocyanate polystyrene (I g; Novabiochem Cat. No.: 01-64-0169) were added. The resulting mixture was shaken for 1 hour and filtered. The filtrate was evaporated and the obtained residue was purified by flash column chromatography (eluent: CH2CyCH3OH 90/10). The product fractions were collected and the solvent was evaporated, yielding 0.144 g of compound 7.

References: [1]Patent: WO2006/24627,2006,A2 .Location in patent: Page/Page column 46; 55.

15
[ 117755-95-0 ]
[ 62058-03-1 ]
C₂₁H₃₀N₂O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
44%		Example B.11 Preparation of compound 34; To a mixture of 2-methyl-iV-o-tolyl-alanine [117755-95-0] (0.006 mol), EDCI (0.009 mol), HOBt (0.009 mol), NMM (0.024 mol) and CH2Cl2 (80 ml), a solution of (lalpha,3alpha,4alpha,5beta,7alpha)-4-amino-tricyclo[3.3.1.13'7]decan-l-ol [62058-03-1] (0.006 mol) in DMF (20 ml) was added after 10 minutes. The reaction mixture was stirred for 16 hours at 20°C under N2 flow. The mixture was poured out into a column comprising diatomaceous earth. Then the column was washed with CH3OH/CH2C12 5/95. The filtrate was purified by flash chromatography (eluent: CH3OH(2-3percent)/CH2Cl2) over SiO2, yielding 0.89 g (44percent) of compound 34

References: [1]Patent: WO2006/24627,2006,A2 .Location in patent: Page/Page column 48; 59.

16
[ 23438-11-1 ]
[ 62058-03-1 ]
C₂₁H₂₉NO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
54%		Example B.16 a) Preparation of compound 13; To a mixture of 2-methyl-2-(4-methylphenoxy)propanoic acid [23438-11-1] (0.015 mol) and DMF (100 ml), HOBt (0.0165 mol) was added at room temperature. The reaction mixture was stirred until complete dissolution. EDCI (0.0165 mol) was added and the mixture was stirred at room temperature for 30 minutes. (lalpha,3alpha,4alpha,5beta,7alpha)- 4-amino-tricyclo[3.3.1.13'7]decan-l-ol [62058-03-1] (0.0165 mol) was added and the mixture was stirred at room temperature for 3 hours. The solvent was evaporated. The residue was purified by column chromatography (eluent: CH2CyCH3OH 100/0 to 98/2). The product fractions were collected and the solvent was evaporated, yielding 0.29Og (54percent) of compound 13

References: [1]Patent: WO2006/24627,2006,A2 .Location in patent: Page/Page column 50; 55.

17
[ 17413-74-0 ]
[ 62058-03-1 ]
C₂₀H₂₆ClNO₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Example B .4 a) Preparation of compound 4; A mixture of 2-[(4-chlorophenyl)thio]-2-methylpropanoic acid [17413-74-0] (0.0007 mol) in dichloromethane (5 ml), DMF (5 ml) and DIPEA (0.5 ml) was stirred and l-[bis(dimethylamino)methylene]-lH-benzotriazolium, hexafluorophosphate(l-), 3-oxide (EtaBTU)(0.0075 mol) was added. After stirring for 15 minutes (lalpha,3alpha,4alpha,5beta,7alpha) -4-aminotricyclo[3.3.1.13'7]decan-l-ol [62058-03-1] (0.00075 mol) was added. The reaction mixture was stirred overnight at 40°C and the solvent was evaporated. The residue was dissolved in dichloromethane and then the solution was washed with a 15 percent citric acid solution and with a sodium carbonate solution. The organic layer was separated, dried, filtered off and the solvent was evaporated. The obtained residue was purified by column chromatography over silica gel (Supelco) (eluent: dichloromethane). The product fractions were collected and the solvent was evaporated, yielding 0.164 g of compound 4.

References: [1]Patent: WO2006/24627,2006,A2 .Location in patent: Page/Page column 44-45; 56.

18
[ 42936-88-9 ]
[ 62058-03-1 ]
C₂₁H₂₈ClNO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Example B.I Preparation of compound 1; 1 -Hydroxy- lH-benzotriazo Ie (0.0007 mol) was added to a solution of intermediate 1 (0.0006 mol) in dichloromethane (10 ml) and DMF (5 ml) and the mixture was stirred for 10 minutes. Then JV"-(ethylcarbonimidoyl)-iV,iV-dimethyl- 1,3-propanediamine, monohydrochloride [25952-53-8] (0.0007 mol) was added and the mixture was stirred for 20 minutes. After addition of (lalpha,3alpha,4alpha,5beta,7alpha)- 4-aminotricyclo[3.3.1.13'7]decan-l-ol [62058-03-1] (0.0007 mol), the reaction mixture was stirred overnight and the solvent was evaporated. The obtained residue was dissolved in dichloromethane and then washed with a 15 percent citric acid solution and with a Na2CO3 solution. The organic layer was dried through Extrelut and the solvent was evaporated, yielding 0.17O g of compound 1.

References: [1]Patent: WO2006/24627,2006,A2 .Location in patent: Page/Page column 43; 56.

19
[ 1000052-78-7 ]
[ 62058-03-1 ]
tert-butyl {(2S,3S,5R)-1-[4-(2-chlorophenyl)-2,2-dimethyl-5-oxopiperazin-1-yl]-3-hydroxy-5-[(2s,5s)-5-(hydroxyadamantan-2-yl)carbamoyl]heptan-2-yl}carbamate [ No CAS ]

References: [1]ACS Medicinal Chemistry Letters,2012,vol. 3,p. 754 - 758.

20
[ 1431330-66-3 ]
[ 62058-03-1 ]
C₂₄H₃₀N₄O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: To a solution of ethyl 1-phenyl-5-(2-methyl-4-oxobutan-2-yl)-1H-pyrazole-4-carboxylate 14b (45 mg, 0.15 mmol) in CHCl3 (9 mL) was added trans-<strong>[62058-03-1]5-hydroxy-2-adamantylamine</strong> (25 mg, 0.15 mmol), acetic acid (0.025 mL, 0.45 mmol) and sodium triacetoxyborohydride (85 mg, 0.45 mmol) at room temperature. After stirring at ambient temperature for 16 hours, the reaction mixture was quenched with aq. NaHCO3, extracted with CHCl3, and washed with aq. NaCl. The combined organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was dissolved in methanol (0.30 mL), and added 1.0 N NaOH (0.22 mL, 0.22 mmol) at room temperature. After stirring at ambient temperature for 16 hours, the solvent was removed under vacuum. The mixture of the residue in CHCl3 (1.5 mL) and DIPEA (0.078 mL, 0.45 mmol) and HBTU (35 mg, 0.15 mmol) was stirred at room temperature. After 16 hours, the reaction mixture was quenched with aq. NaHCO3, extracted with CHCl3, and washed with aq. NaCl., then purified with column chromatography (silica gel, eluting with CHCl3/methanol) to give the title compound as a white solid (0.025 g, 42 percent yield).