881189-74-8|6-Bromo-4-fluoro-2,3-dihydro-1H-inden-1-one| Ambeed

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Quality Control of [ 881189-74-8 ] Purity: 95% SDS Specification

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Product Details of [ 881189-74-8 ]

CAS No. :	881189-74-8
Formula :	C₉H₆BrFO
M.W :	229.05
SMILES Code :	O=C1CCC2=C1C=C(Br)C=C2F
MDL No. :	MFCD14654077
Boiling Point :	No data available
InChI Key :	FVPXVDTWEBFLLE-UHFFFAOYSA-N
Pubchem ID :	50989426

Safety of [ 881189-74-8 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302
Precautionary Statements:	P280-P305+P351+P338

Computational Chemistry of [ 881189-74-8 ] Show Less

Physicochemical Properties

Num. heavy atoms	12
Num. arom. heavy atoms	6
Fraction Csp3	0.22
Num. rotatable bonds	0
Num. H-bond acceptors	2.0
Num. H-bond donors	0.0
Molar Refractivity	47.15
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	17.07 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.11
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	2.46
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	3.14
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.	2.84
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	3.82
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.87

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-3.18
Solubility	0.151 mg/ml ; 0.000661 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.	-2.46
Solubility	0.79 mg/ml ; 0.00345 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	-4.25
Solubility	0.0127 mg/ml ; 0.0000556 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	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.	-5.95 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)	1.99

Application In Synthesis of [ 881189-74-8 ]

* 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 [ 881189-74-8 ]

[ 881189-74-8 ] Synthesis Path-Downstream 1~33

2
[ 881189-74-8 ]
[ 1400702-00-2 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylsilane; trifluoroacetic acid; at 20℃;	To a solution of 6-bromo-4-fluoroindan-l-one (57 mg, 0.26 mmol) in trifluoroacetic acid (1.1 mL) was added triethylsilane (103 ih, 0.65 mmol), and the mixture was stirred at room temperature overnight. The reaction solution was poured into ice water, and the mixture was extracted with ethyl acetate three times. The organic layer was combined, washed with saturated aqueous sodium hydrogen carbonate solution, and the organic layer was filtered through Phase-separator (Varian Inc.), and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate = 100:0) to give a crude 6-bromo-4-fluoroindane (61 mg) as a yellow oil. The resultant was used in the next step without further purification.

References: [1]Patent: WO2012/124825,2012,A1 .Location in patent: Page/Page column 142; 143.

3
[ 881189-74-8 ]
[ 1593700-28-7 ]
[ 1593697-33-6 ]

Yield	Reaction Conditions	Operation in experiment
	With copper(l) iodide; caesium carbonate; N,N`-dimethylethylenediamine; In 1,4-dioxane; at 85℃; for 3h;Inert atmosphere;	Alternative Preparation of (R)-3-[6-(2-Cyclopropyl-ethoxy)-pyridin-3-yloxv]-1-(7-fluoro-3-oxo-indan-5-yl)-pyrrolidin-2-one (Example 1-08) A mixture of (R)-3-[6-(2-cyclopropyl-ethoxy)-pyridin-3-yloxy]-pyrrolidin-2-one (100 mg), <strong>[881189-74-8]6-bromo-4-fluoro-2,3-dihydro-1H-inden-1-one</strong> (87 mg) and 1,4-dioxane (2 mL) was purged with argon. N,N'-Dimethyl-ethylene-diamine (336 mg), cesium carbonate (248 mg) and copper(I) iodide (7 mg) were added. The mixture was heated to 85 C. for 3 hours. After cooling to r.t. the mixture was filtered and the filtrate purified by preparative HPLC to provide Example 1-08. 1H-NMR (400 MHz, DMSO) 67.99 (1H, dd, J=11.3, 1.8 Hz), 7.97 (1H, d, J=3.1 Hz), 7.77 (1H, d, J=1.8 Hz), 7.53 (1H, dd, J=9.0, 3.1 Hz), 6.77 (1H, d, J=9.0 Hz), 5.22 (1H, dd, J=8.3, 8.3 Hz), 4.24 (2H, t, J=6.8 Hz), 3.96 (1H, m), 3.86 (1H, m), 3.10 (2H, m), 2.72 (2H, m), 2.69 (1H, m), 2.14 (1H, m), 1.60 (2H, dt, J=6.8, 6.8 Hz), 0.80 (1H, m), 0.42 (2H, m), 0.10 (2H, m).
	With copper(l) iodide; caesium carbonate; N,N`-dimethylethylenediamine; In 1,4-dioxane; at 85℃; for 3h;Inert atmosphere;	A mixture of (R)-3-[6-(2-cyclopropyl-ethoxy)-pyridin-3-yloxy]-pyrrolidin-2-one (100 mg), 6-bromo-4-fluoro-2,3-dihydro-1 H-inden-1 -one (87 mg) and 1 ,4-dioxane (2 mL) was purged with argon. Lambda/,Lambda/'-Dimethyl-ethylene-diamine (336 mg), cesium carbonate (248 mg) and copper(l) iodide (7 mg) were added. The mixture was heated to 85C for 3 hours. After cooling to r.t. the mixture was filtered and the filtrate purified by preparative HPLC to provide Example 1 -08. 1H-NMR (400 MHz, DMSO) 5 7.99 (1 H, dd, J = 1 1 .3, 1 .8 Hz), 7.97 (1 H, d, J = 3.1 Hz), 7.77 (1 H, d, J= 1 .8 Hz), 7.53 (1 H, dd, J= 9.0, 3.1 Hz), 6.77 (1 H, d, J = 9.0 Hz), 5.22 (1 H, dd, J = 8.3, 8.3 Hz), 4.24 (2H, t, J = 6.8 Hz), 3.96 (1 H, m), 3.86 (1 H, m), 3.10 (2H, m), 2.72 (2H, m), 2.69 (1 H, m), 2.14 (1 H, m), 1 .60 (2H, dt, J = 6.8, 6.8 Hz), 0.80 (1 H, m), 0.42 (2H, m), 0.10 (2H, m).

References: [1]Patent: US2014/99333,2014,A1 .Location in patent: Paragraph 0266; 0267.
[2]Patent: WO2014/56938,2014,A1 .Location in patent: Page/Page column 42.

4
[ 881189-74-8 ]
[ 1593699-48-9 ]

References: [1]Patent: US2014/99333,2014,A1 .
[2]Patent: WO2014/56938,2014,A1 .

5
[ 881189-74-8 ]
[ 1593701-18-8 ]
[ 1593697-75-6 ]

Yield	Reaction Conditions	Operation in experiment
	With copper(l) iodide; caesium carbonate; N,N`-dimethylethylenediamine; In 1,4-dioxane; at 100℃; for 1.5h;Inert atmosphere;	Alternative Preparation of (R)-3-(6-Ethoxy-pyridin-3-yloxy)-1-(7-fluoro-3-oxo-indan-5-yl)-pyrrolidin-2-one (Example 2-08) To a mixture of (R)-1-(7-fluoro-3-oxo-indan-5-yl)-3-(6-hydroxy-pyridin-3-yloxy)-pyrrolidin-2-one (60 mg), ethanol (23 mg) and solvent (THF/DCM/NMP 4:4:1, 5 mL) under argon was added triphenylphosphine (polymer, 0.4 mmol). After 5 minutes DIAD (51 mg) was added. The mixture was shaken at 40 C. for 12 hours. The mixture was filtered and the filtrate was concentrated. The residue was purified by preparative HPLC to provide Example 2-08. In a further alternative preparation a mixture of (R)-3-((6-ethoxypyridin-3-yl)oxy)pyrrolidin-2-one (2.00 g), <strong>[881189-74-8]6-bromo-4-fluoro-2,3-dihydro-1H-inden-1-one</strong> (2.30 g), N,N'-dimethyl-ethylene-diamine (10 mL) and 1,4-dioxane (20 mL) was purged with argon and cesium carbonate (3.8 g) and copper(I) iodide (100 mg) were added. The mixture was heated to 100 C. for 1.5 hours. After cooling to r.t. the mixture was diluted with EA and washed with water (5 times) and brine. The organic layer was dried (Na2SO4) and concentrated. The residue was purified by SGC (eluent: heptane with 0 to 70% EA) to provide Example 2-08. 1H-NMR (400 MHz, DMSO) delta 7.99 (1H, dd, J=11.3, 1.8 Hz), 7.97 (1H, d, J=3.1 Hz), 7.77 (1H, d, J=1.8 Hz), 7.53 (1H, dd, J=8.9, 3.1 Hz), 6.76 (1H, d, J=8.9 Hz), 5.22 (1H, dd, J=8.3, 8.3 Hz), 4.24 (2H, q, J=7.0 Hz), 3.96 (1H, m), 3.86 (1H, m), 3.11 (2H, m), 2.72 (2H, m), 2.69 (1H, m), 2.13 (1H, m), 1.30 (3H, t, J=7.0 Hz).
	With copper(l) iodide; caesium carbonate; N,N`-dimethylethylenediamine; In 1,4-dioxane; at 100℃; for 1.5h;Inert atmosphere;	In a further alternative preparation a mixture of (R)-3-((6-ethoxypyridin-3- yl)oxy)pyrrolidin-2-one (2.00 g), 6-bromo-4-fluoro-2,3-dihydro-1 H-inden-1 -one (2.30 g), Lambda/,Lambda/'-dimethyl-ethylene-diamine (10 mL) and 1 ,4-dioxane (20 mL) was purged with argon and cesium carbonate (3.8 g) and copper(l) iodide (100 mg) were added. The mixture was heated to 100C for 1 .5 hours. After cooling to r.t. the mixture was diluted with EA and washed with water (5 times) and brine. The organic layer was dried (Na2SO4) and concentrated. The residue was purified by SGC (eluent: heptane with 0 to 70% EA) to provide Example 2-08. 1H-NMR (400 MHz, DMSO) delta 7.99 (1 H, dd, J = 1 1 .3, 1 .8 Hz), 7.97 (1 H, d, J = 3.1 Hz), 7.77 (1 H, d, J = 1 .8 Hz), 7.53 (1 H, dd, J = 8.9, 3.1 Hz), 6.76 (1 H, d, J = 8.9 Hz), 5.22 (1 H, dd, J = 8.3, 8.3 Hz), 4.24 (2H, q, J = 7.0 Hz), 3.96 (1 H, m), 3.86 (1 H, m), 3.1 1 (2H, m), 2.72 (2H, m), 2.69 (1 H, m), 2.13 (1 H, m), 1 .30 (3H, t, J = 7.0 Hz).

References: [1]Patent: US2014/99333,2014,A1 .Location in patent: Paragraph 0302; 0303.
[2]Patent: WO2014/56938,2014,A1 .Location in patent: Page/Page column 59.

6
[ 881189-74-8 ]
[ 1593700-31-2 ]
[ 1593697-39-2 ]

Yield	Reaction Conditions	Operation in experiment
	With copper(l) iodide; caesium carbonate; N,N`-dimethylethylenediamine; In 1,4-dioxane; at 80℃; for 4h;Inert atmosphere;	Alternative Preparation of (R)-3-(6-Cyclopropylmethoxy-pyridin-3-yloxy)-1-(7-fluoro-3-oxo-indan-5-yl)-pyrrolidin-2-one (Example 1-11) A mixture of (R)-3-[6-(2-cyclopropyl-methoxy)-pyridin-3-yloxy]-pyrrolidin-2-one (100 mg), <strong>[881189-74-8]6-bromo-4-fluoro-2,3-dihydro-1H-inden-1-one</strong> (92 mg) and 1,4-dioxane (2 mL) was purged with argon. N,N'-Dimethyl-ethylene-diamine (355 mg), cesium carbonate (263 mg) and copper(I) iodide (8 mg) were added. The mixture was heated to 80 C. for 4 hours. After cooling to r.t. the mixture was filtered and the filtrate purified by preparative HPLC to provide Example 1-11. 1H-NMR (400 MHz, DMSO) delta 7.99 (1H, dd, J=11.2, 1.8 Hz), 7.95 (1H, d, J=3.1 Hz), 7.77 (1H, d, J=1.8 Hz), 7.53 (1H, dd, J=9.0, 3.1 Hz), 6.79 (1H, d, J=9.0 Hz), 5.22 (1H, dd, J=8.3, 8.3 Hz), 4.03 (2H, d, J=7.1 Hz), 3.96 (1H, m), 3.86 (1H, m), 3.10 (2H, m), 2.72 (2H, m), 2.68 (1H, m), 2.13 (1H, m), 1.22 (1H, m), 0.54 (2H, m), 0.30 (2H, m).
	With copper(l) iodide; caesium carbonate; N,N`-dimethylethylenediamine; In 1,4-dioxane; at 80℃; for 4h;Inert atmosphere;	A mixture of (R)-3-[6-(2-cyclopropyl-methoxy)-pyridin-3-yloxy]-pyrrolidin-2-one (100 mg), 6-bromo-4-fluoro-2,3-dihydro-1 H-inden-1 -one (92 mg) and 1 ,4-dioxane (2 mL) waspurged with argon. Lambda/,Lambda/'-Dinnethyl-ethylene-diannine (355 mg), cesium carbonate (263 mg) and copper(l) iodide (8 mg) were added. The mixture was heated to 80C for 4 hours. After cooling to r.t. the mixture was filtered and the filtrate purified by preparative HPLC to provide Example 1 -1 1 . 1 H-NMR (400 MHz, DMSO) 5 7.99 (1 H, dd, J = 1 1 .2, 1 .8 Hz), 7.95 (1 H, d, J = 3.1 Hz), 7.77 (1 H, d, J = 1 .8 Hz), 7.53 (1 H, dd, J = 9.0, 3.1 Hz), 6.79 (1 H, d, J = 9.0 Hz), 5.22 (1 H, dd, J = 8.3, 8.3 Hz), 4.03 (2H, d, J = 7.1 Hz), 3.96 (1 H, m), 3.86 (1 H, m), 3.10 (2H, m), 2.72 (2H, m), 2.68 (1 H, m), 2.13 (1 H, m), 1 .22 (1 H, m), 0.54 (2H, m), 0.30 (2H, m).

References: [1]Patent: US2014/99333,2014,A1 .Location in patent: Paragraph 0267; 0268.
[2]Patent: WO2014/56938,2014,A1 .Location in patent: Page/Page column 42; 43.

7
[ 881189-74-8 ]
[ 1593700-31-2 ]
[ 1593699-97-8 ]

References: [1]Patent: US2014/99333,2014,A1 .
[2]Patent: WO2014/56938,2014,A1 .

8
[ 34368-52-0 ]
[ 881189-74-8 ]
[ 1593701-30-4 ]

Yield	Reaction Conditions	Operation in experiment
	With copper(l) iodide; caesium carbonate; N,N`-dimethylethylenediamine; In 1,4-dioxane; at 80℃; for 3h;Inert atmosphere;	(S)-1-(7-Fluoro-3-oxo-indan-5-yl)-3-hydroxy-pyrrolidin-2-one A mixture of <strong>[881189-74-8]6-bromo-4-fluoro-indan-1-one</strong> (Enamine, 453 mg), (S)-3-hydroxy-pyrrolidin-2-one (200 mg) and 1,4-dioxane (3 mL) was purged with argon. Cesium carbonate (645 mg), N,N'-dimethyl-ethylene-diamine (2.24 mL) and copper(I) iodide (38 mg) were added and the mixture was heated to 80° C. for 3 hours. After cooling to r.t. the mixture was filtered and the filtrate evaporated. The residue was purified by SGC (eluent: heptane/EA 1:1 with 0 to 20percent MeOH) to provide the title compound. MS ESI+: m/z=250 [M+H]+.
	With copper(l) iodide; caesium carbonate; N,N`-dimethylethylenediamine; In 1,4-dioxane; at 80℃; for 3h;Inert atmosphere;	A mixture of 6-bromo-4-fluoro-indan-1 -one (Enamine, 453 mg), (S)-3-hydroxy-pyrrolidin- 2-one (200 mg) and 1 ,4-dioxane (3 mL) was purged with argon. Cesium carbonate (645 mg), Lambda/,Lambda/'-dimethyl-ethylene-diamine (2.24 mL) and copper(l) iodide (38 mg) were added and the mixture was heated to 80°C for 3 hours. After cooling to r.t. the mixture was filtered and the filtrate evaporated. The residue was purified by SGC (eluent: heptane/EA 1 :1 with 0 to 20percent MeOH) to provide the title compound. MS ESI+: m/z = 250 [M+H]+.

References: [1]Patent: US2014/99333,2014,A1 .Location in patent: Paragraph 0309; 0310.
[2]Patent: WO2014/56938,2014,A1 .Location in patent: Page/Page column 63.

9
[ 881189-74-8 ]
[ 96-32-2 ]
methyl 2-(6-bromo-4-fluoro-1-oxo-2,3-dihydro-1H-inden-2-yl)acetate [ No CAS ]
(6-bromo-4-fluoro-2-methoxycarbonylmethyl-1-oxoindan-2-yl)acetic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Methyl 2-(6-bromo-4-fluoro-1 -oxo-2,3-dihydro-1 H-inden-2-yl)acetate To a mixture of diisopropylamine (1 .4 mL) and THF (25 mL) was added n-BuLi (3.4 mL, 2.6 M in toluene) at -78C. After 30 minutes a solution of 6-bromo-4-fluoro-2,3-dihydro- 1 H-inden-1 -one (2.0 g) in THF (10 mL) was added dropwise. After 30 minutes methyl 2- bromoacetate (1 .34 g) was added dropwise. The mixture was allowed to warm to RT with stirring for 2 hours. The mixture was poured into an ammonium chloride solution (10%, aqueous) and then extracted with EA (100 ml_ x 3). The organic phase was washed with brine and then dried over Na2SO4. The solvent was removed by evaporation under reduced pressure and the residue was purified by SGC (heptane to EA/heptane = 4:1 ) to provide the title compound. MS ESI+: m/z = 301 [M+H]+. As a second product (6-bromo-4-fluoro-2-methoxycarbonylmethyl-1 -oxo-indan-2-yl)-acetic acid methyl ester was isolated. MS ESI+: m/z = 373 [M+H]+.

References: [1]Patent: WO2015/150563,2015,A1 .Location in patent: Page/Page column 46-47.

10
[ 881189-74-8 ]
2-[6-[(3R)-3-[[6-(cyclopropylmethoxy)-3-pyridyl]oxy]-2-oxopyrrolidin-1-yl]-4-fluoro-2-(2-methoxy-2-oxoethyl)-1-oxoindan-2-yl]acetic acid [ No CAS ]

References: [1]Patent: WO2015/150563,2015,A1 .

11
[ 881189-74-8 ]
6-bromo-4-fluoro-2-(2-hydroxyethyl)indan-1-ol [ No CAS ]

References: [1]Patent: WO2015/150563,2015,A1 .

12
[ 881189-74-8 ]
6-bromo-4-fluoro-2-(2-hydroxyethyl)-2,3-dihydro-1H-inden-1-one [ No CAS ]

References: [1]Patent: WO2015/150563,2015,A1 .

13
[ 881189-74-8 ]
[ 1248125-21-4 ]

Yield	Reaction Conditions	Operation in experiment
92%	With sodium tetrahydroborate; In methanol; at 20℃; for 2h;	To a solution of <strong>[881189-74-8]6-bromo-4-fluoroindan-1-one</strong> (Sigma-Aldrich, cat No.775819: 120 mg, 0.54 mmol) in methanol (2 mL) was added sodium tetrahydroborate (22 mg, 0.60 mmol) in 2 portions. The reaction mixture was stirred at room temperature for 2 h leading to complete conversion. The solvent was removed and the residue partitioned between water and EtOAc. The EtOAc layer was washed with brine, dried over sodium sulfate, and the solvent was removed to the desired product (115 mg, 92%) which was used in the next step without further purification. LC-MS calculated for C9H7BrF (M+H-H2O)+: m/z=213.0. found 213.0.

References: [1]Patent: US2016/9720,2016,A1 .Location in patent: Paragraph 0520.

14
[ 881189-74-8 ]
[ 7486-35-3 ]
4-fluoro-6-vinylindan-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.235 g	With tetrakis(triphenylphosphine) palladium(0); In toluene;Reflux;	(0339) A mixture of <strong>[881189-74-8]6-bromo-4-fluoroindan-1-one</strong> (0.36 g), tetrakis(triphenylphosphine)palladium(0) (0.182 g), tributylvinyltin (600 muL) and toluene (6 mL) was stirred overnight under reflux. The reaction mixture was allowed to cool to room temperature, to the mixture were added an aqueous solution of 0.5 mol/L potassium fluoride and ethyl acetate, and the mixture was stirred for 0.5 hours at room temperature. The insoluble material was removed by filtration through a pad of Celite. The organic layer of the filtrate was washed with water and brine successively, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography (eluent:ethyl acetate/n-hexane=0/100 to 15/85) to afford the title compound (0.235 g). The structural formula is shown in Table 2. (0340) 1H-NMR (CDCl3) delta: 2.72-2.77 (2H, m), 3.11-3.17 (2H, m), 5.37 (1H, d, J=10.8 Hz), 5.81 (1H, d, J=17.5 Hz), 6.72 (1H, dd, J=10.8, 17.5 Hz), 7.33 (1H, dd, J=1.2, 9.8 Hz), 7.56-7.59 (1H, m).
0.235 g	With tetrakis(triphenylphosphine) palladium(0); In toluene;Reflux;	A mixture of <strong>[881189-74-8]6-bromo-4-fluoroindan-1-one</strong> (0.36 g), tetrakis(triphenylphosphine)palladium(0) (0.182 g), tributylvinyltin (600 muL) and toluene (6 mL) was stirred overnight under reflux. The reaction mixture was allowed to cool to room temperature, to the mixture were added an aqueous solution of 0.5 mol/L potassium fluoride and ethyl acetate, and the mixture was stirred for 0.5 hours at room temperature. The insoluble material was removed by filtration through a pad of Celite. The organic layer of the filtrate was washed with water and brine successively, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography (eluent:ethyl acetate/n-hexane=0/100 to 15/85) to afford the title compound (0.235 g). Read more: http://www.patentsencyclopedia.com/app/20160115119ixzz49dlaUClX
0.235 g	With tetrakis(triphenylphosphine) palladium(0); In toluene;Reflux;	<strong>[881189-74-8]6-bromo-4-fluoro-indan-1-one</strong> (0.36 g), tetrakis (triphenylphosphine) palladium (0) (0.182 g), heated to reflux for tributyl vinyl tin (600 uL) and toluene(6 mL) below, and the mixture was stirred overnight. The reaction mixture was allowed to cool to room temperature, added 0.5 mol / L aqueouspotassium fluoride solution and ethyl acetate, and stirred for 0.5 hours at room temperature. The insoluble material was removed by filtration throughCelite. The organic layer of the filtrate was washed successively with water and brine, dried over anhydrous magnesium sulfate. The solvent wasobtained by vacuum distillation residue was purified by silica gel column chromatography (eluting solvent ethyl acetate / n-hexane = 0 / 100-15 / 85)to give the title compound (0.235 g).

References: [1]Patent: US2016/115119,2016,A1 .Location in patent: Paragraph 0339-0340.
[2]Patent: CN105263901,2016,A .Location in patent: Page/Page column 33; 34.
[3]Patent: JP2016/94407,2016,A .Location in patent: Paragraph 0096; 0097.

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[ 881189-74-8 ]
7-bromo-5-fluoro-1,2,3,4-tetrahydroisoquinolin-1-one [ No CAS ]
7-bromo-5-fluoro-1,2,3,4-tetrahydroquinolin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium azide; methanesulfonic acid; In dichloromethane; at 0 - 20℃; for 1.5h;	A solution of 6-bromo-4-fluoro-2,3-dihydro-lH-inden-l-one (500 mg, 2.18 mmol) in a mixture of DCM (13 mL) and methanesulfonic acid (6.5 mL) at 0C was treated slowly with sodium azide (115.32 mu, 3.27 mmol). The resulting mixture warmed to r.t. and stirred for 1.5 h. Ceric ammonium nitrate solution (5.5% in water, 25 mL) was added slowly and the mixture was partitioned between DCM (50 mL) and water (25 mL). The aqueous layer was extracted with DCM (50 mL), and the combined organic layers were washed with water (25 mL) and brine (25 mL), then dried (MgS04). The solvent was removed in vacuo to give a mixture (1 :1) of the title compounds (410 mg), that was used without separation

References: [1]Patent: WO2016/198400,2016,A1 .Location in patent: Page/Page column 98.

16
C₉H₇BrClFO [ No CAS ]
[ 881189-74-8 ]