380894-77-9|Diethyl ((5-(3-fluorophenyl)pyridin-2-yl)methyl)phosphonate| Ambeed

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Quality Control of [ 380894-77-9 ] Purity: 97% SDS Specification

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Product Details of [ 380894-77-9 ]

CAS No. :	380894-77-9
Formula :	C₁₆H₁₉FNO₃P
M.W :	323.30
SMILES Code :	FC1=CC(C2=CN=C(CP(OCC)(OCC)=O)C=C2)=CC=C1
MDL No. :	MFCD22376876
InChI Key :	CPOPYWOLIYKTLP-UHFFFAOYSA-N
Pubchem ID :	16743266

Safety of [ 380894-77-9 ]

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

Computational Chemistry of [ 380894-77-9 ] Show Less

Physicochemical Properties

Num. heavy atoms	22
Num. arom. heavy atoms	12
Fraction Csp3	0.31
Num. rotatable bonds	7
Num. H-bond acceptors	5.0
Num. H-bond donors	0.0
Molar Refractivity	84.66
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	58.23 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.85
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	2.39
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	4.92
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.	2.32
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	3.57
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	3.21

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-3.29
Solubility	0.165 mg/ml ; 0.000511 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.	-3.25
Solubility	0.18 mg/ml ; 0.000557 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	-6.29
Solubility	0.000167 mg/ml ; 0.000000518 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Poorly 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	Yes
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	Yes
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	Yes
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-6.58 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<0.0
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)	3.46

Application In Synthesis of [ 380894-77-9 ]

* 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 [ 380894-77-9 ]

[ 380894-77-9 ] Synthesis Path-Downstream 1~35

1
[ 380893-73-2 ]
[ 768-35-4 ]
[ 380894-77-9 ]

Yield	Reaction Conditions	Operation in experiment
75%	With sodium carbonate;5%-palladium/activated carbon; In 2-methylpropyl acetate; water; at 70 - 80℃; for 3h;	Example 1; Preparation of [5-(3-Fluoro-phenyl)-pyridin-2-ylmethyl]-phosphonic acid diethyl ester; To a reaction vessel was charged (100 g, 0.29 mol) of phosphonate compound 139 (where R9 is ethyl- for all occurrences), 5% Pd/C 50% wet (5.0 g), 3-fluorophenylboronic acid (61 g; 0.44 mol) and sodium carbonate (100 g; 0.94 mol). 600 ml of iso-butyl acetate was charged and the mixture agitated. 400 ml of water was charged, and the agitated mixture was heated to 70-80 C. for at least 3 h at which time an HPLC assay indicated complete reaction. Upon completion, the reaction mixture was cooled to 25 C. and filtered to remove the Pd/C catalyst. The catalyst cake was washed with 200 ml iso-butyl acetate (combined with the filtrate/batch) and 100 ml water (waste). 25% sodium hydroxide solution was used to adjust batch to pH 11-13. During the process the reaction mixture was maintained at a temperature of from 20 C. to 30 C. The organic layer was separated and washed with 500 ml water with agitation. A 25% sodium hydroxide solution was used to adjust the pH of the batch to a pH value of from pH 11 to pH13. Throughout the was the temperature was maintained at a value of from about 20 C. to about 30 C. After washing the layers were separated and the organic layer was washed with 300 ml of 2% sodium chloride solution with 10-15 minutes with agitation. The layers were separated and an HPLC assay of the organic layer indicated impurities were reduced to a desirable level. Darco (10 g) was added to the organic layer. The resultant slurry was agitated for 1 hour, and then filtered to remove the de-coloring agent. The filter cake was washed with 200 ml iso-butyl acetate (combined with the filtrate/batch) and the batch was concentrated under reduced pressure to about 200 ml at from 40 C. to 50 C., then cooled to a temperature of from 15 C. to 25 C. Heptanes (1000 ml) were charged into the cold concentrate over 2.5-3 hr, maintaining the temperature at from about 15 C. to 25 C. The mixture was cooled to a temperature of from -15 C. to -5 C. over 3 hr and agitated at the same temperature for 1 hr. The crystalline solid was filtered, washed with 200 ml heptanes, and dried overnight under vacuum at a temperature of from about 25 C. to 35 C. to provide 70.37 g (75%). Mp 61-63 C. 1H NMR (CDCl3) delta 1.3 (t, J=7.05 Hz, 6H), 3.47 (d, J=22.02 Hz, 2H), 4.12 (q, J=7.08 Hz, 4H), 7.10 (ddd, J=8.42, 2.55, 0.88, Hz, 1H), 7.28 (ddd, J=9.85, 2.36, 1.80 Hz, 1 H), 7.36 (dt, J=7.86, 1.27, Hz, 1H), 7.46 (m, 1H), 7.83 (ddd, J=8.1, 2.2, 0.32 Hz, 1H), 8.76 (d, J=2.38, 1H).

References: [1]Patent: US2008/4449,2008,A1 .Location in patent: Page/Page column 13.

2
[ 380894-77-9 ]
[ 1018438-21-5 ]
[ 1018438-22-6 ]

Yield	Reaction Conditions	Operation in experiment
	With n-butyllithium; In tetrahydrofuran;	Step 6: The aldehyde 18, was further reacted with a diethylether 19 under the Emmons-Wadsworth reaction conditions to yield the ketal 20.

References: [1]Patent: US2008/85923,2008,A1 .Location in patent: Page/Page column 35.

3
[ 514203-78-2 ]
[ 380894-77-9 ]
C₂₅H₂₆FNO₃ [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 5147 - 5160.

4
[ 514203-63-5 ]
[ 380894-77-9 ]
C₂₈H₃₁FN₂O₄ [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 5147 - 5160.

5
[ 814-49-3 ]
[ 380894-77-9 ]

Yield	Reaction Conditions	Operation in experiment
85%		To a 10 L three-necked round bottomed flask equipped with an agitator, thermometer and a nitrogen inlet tube, was added 20Og ofCompound 8 (1.07 mol, from Synergetica, Philadelphia, Pennsylvania). THF (1000 mL) was added to dissolve Compound 8. After the solution was cooled to -80 0C to -50 0C, 2.0 M LDA in hexane/THF(1175 mL, 2.2 eq) was added while maintaining the batch temperature below -50 0C. After about 15 minutes of agitation at -800C to -50 0C, diethyl chlorophosphate (185 mL, 1.2 eq) was added while maintaining the batch temperature below -50 0C. The mixture was agitated at a temperature from -800C to - 50 0C for about 15 minutes and diluted with n-heptane (1000 mL). This mixture was warmed up to about -35 0C and quenched with aqueous ammonium chloride (400 g in 1400 mL water) at a temperature below -10 0C. This mixture was agitated at -150C to -10 0C EPO <DP n="32"/>for about 15 minutes followed by agitation at 150C to 25 0C for about 15 minutes. The aqueous layer was split and extracted with toluene (400 mL). The combined organic layers were extracted with 2N hydrochloric acid (700 mL) twice. The product-containing hydrochloric acid layers were combined and added slowly to a mixture of toluene (1200 mL) and aqueous potassium carbonate (300 g in 800 mL water) at a temperature below 30 0C. The aqueous layer was extracted with toluene (1200 mL). The organic layers were combined and concentrated under vacuum to about 600 ml and filtered to remove inorganic salts. To the filtrate was added n-heptane (1000 ml) at about 55 0C. The mixture was cooled slowly to 40 0C, seeded, and cooled further slowly to -10 0C. The resulting slurry was aged at about -10 0C for 1 h, filtered, washed with n- heptane, and dried under vacuum to give a light brown solid (294 g, 85% yield), m.p. 52 0C (DSC onset point). 1H NMR (CDCl3) delta 8.73 (d, J = 1.5 Hz, IH), 7.85 (dd, Ji = 8.0 Hz, J2 = 1.5 Hz, IH), 7.49 (dd, Ji = 8.0 Hz, J2 = 1.3 Hz, IH), 7.42 (m, IH), 7.32 (d, J = 7.8 Hz, IH), 7.24 (m, IH), 7.08 (dt, Ji = 8.3 Hz, J2 = 2.3 Hz, IH), 4.09 (m, 4H), 3.48 (d, J = 22.0 Hz, 2H), 1.27 (t, J = 7.0 Hz, 6H). MS (ESI) for M+H calcd. 324, found 324.

References: [1]Patent: WO2006/76564,2006,A1 .Location in patent: Page/Page column 30-31.

6
[ 380893-73-2 ]
3-fluorophenylboronic acid [ No CAS ]
[ 380894-77-9 ]

Yield	Reaction Conditions	Operation in experiment
75%	With sodium carbonate;5%-palladium/activated carbon; In water; toluene; at 75℃; for 5h;	To a reaction vessel was charged sodium carbonate (8 g; 75.5 mmol), 30 ml of water and stirred until dissolved. To this solution were added 3-fluorophenylboronic acid (6 g; 42.9 mmol) and 5% Pd/ C 50% wet (0.5 g). The toluene solution of Compound 38 from above was then added and the mixture was heated to 75 0C for at least 5 h at which time an HPLC assay indicated complete reaction. Upon completion, the reaction mixture was cooled to 25 C and filtered to remove the Pd/ C catalyst. The layers were separated and the organic layer was washed and concentrated under reduced pressure to about 20ml. Heptane (20 EPO <DP n="50"/>ml) was slowly added, seed ciystals were added, and the mixture was cooled to -10 0C over 2 h. The crystalline solid was filtered, washed with heptane and dried overnight under vacuum at 30 0C to provide 8 g (75%). Mp 61 - 63 C. 5 1.3 (t, J = 7.08 Hz, 3H), 3.42 (s, IH), 3.49 (s, IH), 4.1 (q, J = 7.08 Hz, 2H), 7.04 - 7.11 (m, IH), 7.23 - 7.3 (m, IH), 7.32 - 7.3 (m, IH), 7.32 -7.36 (m, IH), 7.39 -7.48 (m, IH), 7.81 (ddd, J = 8.08, 2.3, 0.41 Hz, IH), 8.74 (d, J = 2.36, IH).

References: [1]Patent: WO2006/76415,2006,A2 .Location in patent: Page/Page column 47-48.

7
[ 380894-77-9 ]
[ 942608-68-6 ]
(10R,10aS)-10-{(E)-2-[5-(3-fluoro-phenyl)-pyridin-2-yl]-vinyl}-1,5,10,10a-tetrahydro-oxazolo[3,4-b]isoquinolin-3-one [ No CAS ]
(10S,10aS)-10-{(E)-2-[5-(3-fluoro-phenyl)-pyridin-2-yl]-vinyl}-1,5,10,10a-tetrahydro-oxazolo[3,4-b]isoquinolin-3-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With titanium(IV) isopropylate; n-butyllithium; In tetrahydrofuran; at 0 - 20℃;	The crude tricyclic aldehyde (compound 10) from step 8 in THF (3 mL) was added to a reaction mixture that was prepared by cooling a solution of <strong>[380894-77-9][5-(3-Fluoro-phenyl)-pyridin-2-ylmethyl]-phosphonic acid diethyl ester</strong> (compound 11) (162 mg, 0.5 mmol) in THF (3 mL) to 0 C. using an ice bath then adding 2.5 M n-BuLi (0.2 mL, 0.5 mmol) and stirring it at 0 C. for 15 min followed by addition of titanium tetraisopropoxide (Ti(O-iPr)4) (142 mg, 0.5 mol) then warming the reaction mixture to room temperature. The reaction mixture, now containing the crude tricyclic aldehyde (compound 10) was stirred at room temperature overnight, diluted with ethyl acetate (50 mL), washed with saturated K-Na-tartrate, dried with MgSO4 and separated by column chromatography, which afforded target compounds 12 and 13, which are isomeric at the benzylic carbon. Target compounds 12: 387 (M+1); Thrombin Receptor Angagonist Activity: 27% inhibition at 1 muM and 13: 387 (M+1); Thrombin Receptor Antagonist Activity: 15% inhibition at 1 muM.

References: [1]Patent: US2007/149518,2007,A1 .Location in patent: Page/Page column 26.

8
[ 380894-77-9 ]
[ 942912-37-0 ]
10-{2-[5-(3-fluoro-phenyl)-pyridin-2-yl]-vinyl}-decahydro-oxazolo[3,4-b]isoquinolin-3-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With titanium(IV) isopropylate; n-butyllithium; In tetrahydrofuran; at 0 - 20℃;	The crude tricyclic aldehyde (compound 15) from step 8b in THF (3 mL) was added to a reaction mixture that was prepared by cooling a solution of <strong>[380894-77-9][5-(3-Fluoro-phenyl)-pyridin-2-ylmethyl]-phosphonic acid diethyl ester</strong> (compound 11) (162 mg, 0.5 mmol) in THF (3 mL) to 0 C. using an ice bath then adding 2.5 M n-BuLi (0.2 mL, 0.5 mmol) and stirring it at 0 C. for 15 min followed by addition of titanium tetraisopropoxide (Ti(O-iPr)4) (142 mg, 0.5 mol) and warming the reaction mixture to room temperature. The reaction mixture, now containing the crude tricyclic aldehyde (compound 10), was stirred at room temperature overnight, diluted with ethyl acetate (50 mL), washed with saturated K-Na-tartrate, dried with MgSO4 and separated by column chromatography, which afforded 25 mg of product (compound 16). 16: 393 (M+1), (Target compound 16 (Thrombin Receptor Ki=12 nM)).

References: [1]Patent: US2007/149518,2007,A1 .Location in patent: Page/Page column 27.

9
[ 380894-77-9 ]
[ 1018327-82-6 ]
[ 1018327-86-0 ]

Yield	Reaction Conditions	Operation in experiment
71%		To a solution of 53 (162 mg, 0.50 mmol) in THF (3.0 mL) at 0 C. was added n-BuLi (0.20 mL, 0.48 mmol) and stirred for 15 minutes. To this was added a solution of 49 (20 mg, 0.08 mmol) in THF (3.0 mL)1 followed by Ti(OiPr)4 (0.15 mL, 0.50 mmol) and stirred for 4 hours. The reaction mixture was washed with H2O, dried over MgSO4 and evaporated. The residue was purified via preparative TLC (Ethyl acetate, 100%) to afford compound 54 (23 mg, 0.06 mmol, 71%). MS: m/z 406 [MH+]; Another alternative preparation of isolactone analogs is presented below. Alcohol 7 was protected as benzyl ether and alpha-oxygenated to provide 42. Dibal reduction followed by Dess-Martin reaction gave formate 44 which was converted to enone 45. Conjugate addition of cyanide followed by reduction and hydrolysis gave lactone 47 which was converted to targets 51, 52 and 54.

References: [1]Patent: US2008/90830,2008,A1 .Location in patent: Page/Page column 32-34.

10
[ 380894-77-9 ]
C₁₆H₂₆O₃ [ No CAS ]
C₂₈H₃₄FNO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Step 5: To a solution of phosphonate 7 (1.07 g, 3.31 mmol, 2 eq.) in 15 ml THF at 0 C. was added a solution of 2.5M BuLi in hexanes (1.32 ml, 3.30 mmol, 2 eq.) and stirred for 20 min. To this was added Ti(OiPr)4 (975 mul, 3.30 mmol, 2 eq.) followed by a solution of aldehyde 6 (440 mg, 1.65 mmol) in 3 ml THF. The mixture was stirred for 1 hr and poured into 100 ml aq. sodium potassium tartrate solution. The aqueous slurry was extracted with 3×30 ml EtOAc and the combined organic phase was washed with 30 ml brine, dried over MgSO4, filtered and evaporated to give a residue. This was purified by chromatography to provide 510 mg of 8. MS: m/e 436.1 (MH+)

References: [1]Patent: US2006/223808,2006,A1 .Location in patent: Page/Page column 14; 16-17.

11
[ 111770-91-3 ]
[ 380894-77-9 ]

References: [1]Patent: WO2011/162562,2011,A2 .
[2]ACS Medicinal Chemistry Letters,2013,vol. 4,p. 1054 - 1058.
[3]Journal of Medicinal Chemistry,2017,vol. 60,p. 7166 - 7185.

12
[ 713143-67-0 ]
[ 814-49-3 ]
[ 380894-77-9 ]

Yield	Reaction Conditions	Operation in experiment
		In anhydrous THF (5 mL) was dissolved the Step 2 compound (0.9 g, 4.80 mmol), to which was added Li i Pr2NH (1.8 M in THF) (3.0 mL, 4.80 mmol) at -78 C. After stirring for 10 min, n-BuLi (1.6 M in THF) (6.0 mL, 9.61 mmol) and diethylchlorophosphonate (0.96 mL, 4.80 mmol) were slowly added. After stirring for 2 h, the mixture was extracted with ethyl acetate and washed twice with saturated aqueous sodium chloride solution. The organic layer was dried over MgSO4 and filtered. The filtrate was concentrated and purified by silica gel column chromatography (CH2Cl2:CH3OH=20:1) to give the title compound (0.55 g, 1.56 mmol). [777] 1H-NMR (300 MHz, CDCl3) delta 1.29(t, J = 6.9 Hz, 7.2 Hz, 6H), 3.46 (d, J = 21.9 Hz, 2H), 4.09~4.16(m, 4H), 7.06~7.12(m, 1H), 7.24~7.49 (m, 4H), 7.82 (dd, J = 2.4 Hz, 2.4 Hz, 1H), 8.76 (d, J = 2.4 Hz, 1H).

References: [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 7166 - 7185.
[2]Patent: WO2011/162562,2011,A2 .Location in patent: Page/Page column 62-63.
[3]ACS Medicinal Chemistry Letters,2013,vol. 4,p. 1054 - 1058.

13
[ 1121-78-4 ]
[ 380894-77-9 ]

References: [1]Patent: WO2011/162562,2011,A2 .
[2]ACS Medicinal Chemistry Letters,2013,vol. 4,p. 1054 - 1058.
[3]Journal of Medicinal Chemistry,2017,vol. 60,p. 7166 - 7185.

14
[ 380894-77-9 ]
(±)-(1R,3aS,7aS)-1-{(E)-2-[5-(3-fluorophenyl)pyridin-2-yl]vinyl}hexahydro-1H-inden-2(3H)-one [ No CAS ]

References: [1]Patent: WO2011/162562,2011,A2 .
[2]ACS Medicinal Chemistry Letters,2013,vol. 4,p. 1054 - 1058.

15
[ 380894-77-9 ]
(+/-)-(1S,3aR,7aR,Z)-1-{(E)-2-[5-(3-fluorophenyl)pyridin-2-yl]vinyl}hexahydro-1H-inden-2(3H)-one oxime [ No CAS ]
(+/-)-(1S,3aR,7aR,E)-1-{(E)-2-[5-(3-fluorophenyl)pyridin-2-yl]vinyl}hexahydro-1H-inden-2(3H)-one oxime [ No CAS ]

References: [1]Patent: WO2011/162562,2011,A2 .

16
[ 380894-77-9 ]
(+/-)-(1S,2S,3aR,7aR)-1-{(E)-2-[5-(3-fluorophenyl)pyridin-2-yl]vinyl}octahydro-1H-inden-2(3H)-ol [ No CAS ]

References: [1]Patent: WO2011/162562,2011,A2 .

17
[ 380894-77-9 ]
(+/-)-5-(3-fluorophenyl)-2-{(E)-2-[(1S,2S,3aR,7aR)-2-methoxyoctahydro-1H-inden-1-yl]vinyl}pyridine [ No CAS ]

References: [1]Patent: WO2011/162562,2011,A2 .

18
[ 380894-77-9 ]
(+/-)-(1S,2S,3aR,7aR)-1-{(E)-2-[5-(3-fluorophenyl)pyridin-2-yl]vinyl}octahydro-1H-inden-2-yl acetate [ No CAS ]

References: [1]Patent: WO2011/162562,2011,A2 .

19
[ 380894-77-9 ]
(+/-)-5-(3-fluorophenyl)-2-{(E)-2-[(1S,2S,3aR,7aR)-2-(benzyloxy)octahydro-1H-inden-1-yl]vinyl}pyridine [ No CAS ]

References: [1]Patent: WO2011/162562,2011,A2 .

20
[ 380894-77-9 ]
(+/-)-(1S,2S,3aR,7aR)-1-{(E)-2-[5-(3-fluorophenyl)pyridin-2-yl]vinyl}octahydro-1H-inden-2-yl methanesulfonate [ No CAS ]

References: [1]Patent: WO2011/162562,2011,A2 .

21
[ 380894-77-9 ]
(+/-)-(1S,2S,3aR,7aR)-1-{(E)-2-[5-(3-fluorophenyl)pyridin-2-yl]vinyl}octahydro-1H-inden-2-yl phenylcarbamate [ No CAS ]

References: [1]Patent: WO2011/162562,2011,A2 .

22
[ 380894-77-9 ]
(+/-)-(1S,2S,3aR,7aR)-1-{(E)-2-[5-(3-fluorophenyl)pyridin-2-yl]vinyl}octahydro-1H-inden-2-yl dimethylcarbamothioate [ No CAS ]

References: [1]Patent: WO2011/162562,2011,A2 .

23
[ 380894-77-9 ]
(±)-(1S,3aS,7aS)-octahydrospiro[[1,3]dioxolane-2,2'-indene]-1-carbaldehyde [ No CAS ]
(±)-5-(3-fluorophenyl)-2-{(E)-2-[(1'R,3a'S,7a'S)-octahydrospiro[(1,3)-dioxolane-2,2'-inden]-1’-yl]vinyl}pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
44%		The Preparation 15 compound (1.4 g, 4.56 mmol) was dissolved in anhydrous THF (15 mL), to which was slowly added n-BuLi (2.5M toluene solution, 1.8 mL) at 0 C. After stirring for 30 min, the Preparation 1 compound (0.5 g, 2.38 mmol) dissolved in THF (10 mL) was slowly added thereto. After stirring for 2 h at room temperature, the mixture was extracted with ethyl acetate and washed twice with saturated aqueous sodium chloride solution. The organic layer was dried over MgSO4 and filtered. The filtrate was concentrated and purified by silica gel column chromatography (hexane:ethyl acetate=10:1) to give the title compound (0.450 g, 44%). [801] 1H-NMR (300 MHz, CDCl3) delta 0.85~1.78 (m, 8H), 2.02~2.18 (m, 4H), 2.84~2.91 (m, 1H), 3.76~3.97 (m, 4H), 6.53~6.76 (m, 2H), 7.05~7.11 (m, 1H), 7.28~7.47 (m, 4H), 7.78 (m, 1H), 8.86 (d, J = 0.4 Hz, 1H).

References: [1]Patent: WO2011/162562,2011,A2 .Location in patent: Page/Page column 65.

24
[ 380894-77-9 ]
[ 380893-74-3 ]
C₂₅H₂₈FNO₂ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 2544 - 2549.

25
[ 380894-77-9 ]
(±)-(1S,3aR,7aS)-octahydrospiro[[1,3]dioxolane-2,2'-indene]-1-carbaldehyde [ No CAS ]
(±)-5-(3-fluorophenyl)-2-{(E)-2-[(1'R,3a'R,7a'S)-octahydrospiro[(1,3)-dioxolane-2,2'-inden]-1’-yl]vinyl}pyridine [ No CAS ]