[ CAS No. 1544739-25-4 ] {[proInfo.proName]}

Name: 1544739-25-4|2-(3-(Bromomethyl)-4-fluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane|97%
Brand: Ambeed
SKU: A534764
Price: 37.0 USD
Availability: InStock
Rating: 95 (22 reviews)

,{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]}

HazMat Fee +

There will be a HazMat fee per item when shipping a dangerous goods. The HazMat fee will be charged to your UPS/DHL/FedEx collect account or added to the invoice unless the package is shipped via Ground service. Ship by air in Excepted Quantity (each bottle), which is up to 1g/1mL for class 6.1 packing group I or II, and up to 25g/25ml for all other HazMat items.

Type	HazMat fee for 500 gram (Estimated)
Excepted Quantity	USD 0.00
Limited Quantity	USD 15-60
Inaccessible (Haz class 6.1), Domestic	USD 80+
Inaccessible (Haz class 6.1), International	USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic	USD 100+
Accessible (Haz class 3, 4, 5 or 8), International	USD 200+

2D 3D

Structure of 1544739-25-4 * Storage: {[proInfo.prStorage]}

Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

For Research Only 110K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 1544739-25-4 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 1544739-25-4 ]

SDS Specification

Alternatived Products of [ 1544739-25-4 ]

Product Details of [ 1544739-25-4 ]

CAS No. :	1544739-25-4	MDL No. :	MFCD23098825
Formula :	C₁₃H₁₇BBrFO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	BQOMTZAOMQFSJP-UHFFFAOYSA-N
M.W :	314.99	Pubchem ID :	75487535
Synonyms :

Calculated chemistry of [ 1544739-25-4 ]

Physicochemical Properties

Num. heavy atoms :	18
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.54
Num. rotatable bonds :	2
Num. H-bond acceptors :	3.0
Num. H-bond donors :	0.0
Molar Refractivity :	75.71
TPSA :	18.46 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	Yes
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	Yes
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.69 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	3.57
Log Po/w (WLOGP) :	3.29
Log Po/w (MLOGP) :	2.8
Log Po/w (SILICOS-IT) :	3.29
Consensus Log Po/w :	2.59

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	0.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-4.16
Solubility :	0.022 mg/ml ; 0.0000697 mol/l
Class :	Moderately soluble
Log S (Ali) :	-3.64
Solubility :	0.0716 mg/ml ; 0.000227 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-5.51
Solubility :	0.000964 mg/ml ; 0.00000306 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	3.24

Safety of [ 1544739-25-4 ]

Signal Word:	Danger	Class:	8
Precautionary Statements:	P201-P202-P261-P264-P270-P271-P280-P302+P352-P304+P340-P308+P313-P310-P330-P361-P403+P233-P405-P501	UN#:	1759
Hazard Statements:	H302-H314	Packing Group:	Ⅲ
GHS Pictogram:

Application In Synthesis of [ 1544739-25-4 ]

* 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 [ 1544739-25-4 ]

[ 1544739-25-4 ] Synthesis Path-Downstream 1~52

1
[ 1544739-07-2 ]
[ 1544739-25-4 ]
[ 1544739-24-3 ]

Yield	Reaction Conditions	Operation in experiment
	With silver carbonate In toluene at 110℃; Inert atmosphere;	2-4.C Step C: 4- [2-Fluoro-5 -(4,4,5,5 -tetramethyl- [1,3,21 dioxaborolan-2-yl)-benzyloxyl -1,1 a,6,6a- tetrahydro-3-aza -cyclopropa[alindene-1-carboxylic acid ethyl ester (2-4) Step C: 4- [2-Fluoro-5 -(4,4,5,5 -tetramethyl- [1,3,21 dioxaborolan-2-yl)-benzyloxyl -1,1 a,6,6a- tetrahydro-3-aza -cyclopropa[alindene-1-carboxylic acid ethyl ester (2-4)To a stirred solution of compound 2-3 (863 mg, 2.74 mmol) and 1-9 (500 mg, 2.28 mmol) intoluene (35 mL), was added Ag2CO3 (1.30 g, 4.56 mmol) in one portion. The resulting mixture was heated to 110°C under N2 protection overnight. TLC showed compound 2-3 was consumed.The mixture was filtered, the filtrate was concentrated to afford crude product which waspurified b by column chromatography on silica gel (PE:EA=5:1) to give 2-4. MS (ESI) mlz: 454 (M+Hj. ‘H-NMR (400 MHz, CDC13) ö: 8.10 (s, 1H), 7.93 (d, 1H, J4.0 Hz), 7.72 (t, 1H, J4.0 Hz), 7.06 (t, 1H, J=2.8 Hz), 6.61 (s, 1H), 5.36 (s, 2H), 4.12 (dd, 2H, J=2.0 and 7.2 Hz), 3.23 (dd, 1H, J=6.0 and 12.0 Hz), 2.98 (d, 1H, J=8.8 Hz), 2.88 (d, 1H, J2.8 Hz), 2.43-2.39 (m, 1H), 1.33(s, 12H), 1.26-1.23 (m, 4H).
	With silver carbonate In toluene at 110℃; Inert atmosphere;	2.4.C Step C: 4-[2-Fluoro-5-( 4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyloxy]-L 1a,6,6atetrahydro-3-aza -cyclopropa[a]indene-1-carboxylic acid ethyl ester (2-4) To a stirred solution of compound 2-3 (863 mg, 2.74 mmol) and 1-9 (500 mg, 2.28 mmol) intoluene (35 mL), was added Ag2C03 (1.30 g, 4.56 mmol) in one portion. The resulting mixturewas heated to 11 0°C under N2 protection overnight. TLC showed compound 2-3 was consumed.5 The mixture was filtered, the filtrate was concentrated to afford crude product which was purifiedb by column chromatography on silica gel (PE:EA=5: 1) to give 2-4. MS (ESI) m/z: 454 (M+H+).1H-NMR (400 MHz, CDCh) 8: 8.10 (s, 1H), 7.93 (d, 1H, J=4.0 Hz), 7.72 (t, 1H, J=4.0 Hz),7.06 (t, 1H, J=2.8 Hz), 6.61 (s, 1H), 5.36 (s, 2H), 4.12 (dd, 2H, J=2.0 and 7.2 Hz), 3.23 (dd, 1H,J=6.0 and 12.0 Hz), 2.98 (d, 1H, J=8.8 Hz), 2.88 (d, 1H, J=2.8 Hz), 2.43-2.39 (m, 1H), 1.33 (s,10 12H), 1.26-1.23 (m, 4H).

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2014/22528, 2014, A1 Location in patent: Page/Page column 90; 91
[2]Current Patent Assignee: MERCK & CO INC - WO2014/19186, 2014, A1 Location in patent: Page/Page column 76; 77

2
[ 99725-13-0 ]
[ 1544739-25-4 ]

Reference： [1]Patent: WO2014/19186,2014,A1

3
[ 73183-34-3 ]
[ 1544739-25-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate / 1,4-dioxane / 110 °C / Inert atmosphere 2: phosphorus tribromide / tetrahydrofuran / 1 h / 0 °C

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2014/19186, 2014, A1 Current Patent Assignee: MERCK & CO INC - WO2014/22528, 2014, A1

4
[ 1352733-99-3 ]
[ 1544739-25-4 ]

Yield	Reaction Conditions	Operation in experiment
	With phosphorus tribromide In tetrahydrofuran at 0℃; for 1h;	2-4.B Step B: 2-(3 -Bromomethyl-4-fluoro-phenyl)-4,4,5 ,5 -tetramethyl- [1,3 ,2ldioxaborolane (2-3) Step B: 2-(3 -Bromomethyl-4-fluoro-phenyl)-4,4,5 ,5 -tetramethyl- [1,3 ,2ldioxaborolane (2-3)To a stirred solution of compound 2-2 (7 g, 28 mmol) in THF (80 mL), was added PBr3 (7.6 g,28 mmol) dropwise at 0 °C. The resulting mixture was stirred at 0 °C for lh. H20 (50 mL) was added to the mixture and the resulting mixture was extracted with EtOAc (50 mL x 3). The combined organic layers were washed with brine, dried over Na2SO4, and concentrated to afford crude product, which was purified b by column chromatography on silica gel (PE:EA=20: 1) to give compound 2-3. MS (ESI) mlz: 315, 316 (M+Hj.
	With phosphorus tribromide In tetrahydrofuran at 0℃; for 1h;	2.4.B Step B: 2-(3-Bromomethyl-4-fluoro-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (2-3) To a stirred solution of compound 2-2 (7 g, 28 mmol) in THF (80 mL), was added PBr3 (7.6 g,15 28 mmol) dropwise at 0 °C. The resulting mixture was stirred at 0 °C for 1h. H20 (50 mL) wasadded to the mixture and the resulting mixture was extracted with EtOAc (50 mL x 3). Thecombined organic layers were washed with brine, dried over Na2S04, and concentrated to affordcrude product, which was purified b by column chromatography on silica gel (PE:EA=20:1) togive compound 2-3. MS (ESI) m/z: 315, 316 (M+H+).
	With bromine; triethylamine; triphenylphosphine In dichloromethane at 0 - 20℃; Inert atmosphere;	55.A Step A. 2-(3-(bromomethyl)-4-fluorophenyl)-4,4,5,5-tetramethyl- 1 ,3,2-dioxaborolane Step A. 2-(3-(bromomethyl)-4-fluorophenyl)-4,4,5,5-tetramethyl- 1 ,3,2-dioxaborolane A methylene chloride solution of bromine (0.698 M, 3 ml, 2.094 mmol) was added slowly to a solution of (2-fluoro-5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2- yl)phenyl)methanol (250 mg, 0.992 mmol), triethylamine (0.15 ml, 1.076 mmol) and triphenylphosphine (547 mg, 2.086 mmol) in dichloromethane (2 ml) at 0°C under N2- The mixture was stirred at RT overnight. The solvent was evaporated. The residue was purified on silica gel using hexane and EtOAc to obtain the title compound. -NMR (500 MHz, CDCI3) δ: 7.84 (dd, 1H), 7.75 (ddd, 1H), 7.06 (dd, 1H), 4.5 (s, 3H), 1.34 (s, 12H).

With bromine; triethylamine; triphenylphosphine In dichloromethane at 0 - 20℃; Inert atmosphere;

55.A Step A. 2-(3-(bromomethyl)-4-fluorophenyl)-4,4,5,5-tetramethyl- 1 ,3,2-dioxaborolane Step A. 2-(3-(bromomethyl)-4-fluorophenyl)-4,4,5,5-tetramethyl- 1 ,3,2-dioxaborolane A methylene chloride solution of bromine (0.698 M, 3 ml, 2.094 mmol) was added slowly to a solution of (2-fluoro-5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2- yl)phenyl)methanol (250 mg, 0.992 mmol), triethylamine (0.15 ml, 1.076 mmol) and triphenylphosphine (547 mg, 2.086 mmol) in dichloromethane (2 ml) at 0°C under N2- The mixture was stirred at RT overnight. The solvent was evaporated. The residue was purified on silica gel using hexane and EtOAc to obtain the title compound. -NMR (500 MHz, CDCI3) δ: 7.84 (dd, 1H), 7.75 (ddd, 1H), 7.06 (dd, 1H), 4.5 (s, 3H), 1.34 (s, 12H).

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2014/22528, 2014, A1 Location in patent: Page/Page column 90
[2]Current Patent Assignee: MERCK & CO INC - WO2014/19186, 2014, A1 Location in patent: Page/Page column 76
[3]Current Patent Assignee: MERCK & CO INC - WO2015/89809, 2015, A1 Location in patent: Page/Page column 95; 96
[4]Current Patent Assignee: MERCK & CO INC - WO2015/95256, 2015, A1 Location in patent: Page/Page column 96

5
[ 1544739-25-4 ]
[ 1544739-49-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: silver carbonate / toluene / 110 °C / Inert atmosphere 2: potassium carbonate; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; tricyclohexylphosphine / water; 1,4-dioxane / 0.17 h / 130 °C / Inert atmosphere; Microwave irradiation
	Multi-step reaction with 2 steps 1: silver carbonate / toluene / 110 °C / Inert atmosphere 2: potassium carbonate; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; tricyclohexylphosphine / water; 1,4-dioxane / 0.17 h / 130 °C / Inert atmosphere; Microwave irradiation

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2014/22528, 2014, A1
[2]Current Patent Assignee: MERCK & CO INC - WO2014/19186, 2014, A1

6
[ 1544739-25-4 ]
[ 1544739-47-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: silver carbonate / toluene / 110 °C / Inert atmosphere 2: potassium carbonate; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; tricyclohexylphosphine / water; 1,4-dioxane / 0.17 h / 130 °C / Inert atmosphere; Microwave irradiation 3: sodium hydroxide; water / methanol / 0.5 h / 50 °C
	Multi-step reaction with 3 steps 1: silver carbonate / toluene / 110 °C / Inert atmosphere 2: potassium carbonate; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; tricyclohexylphosphine / water; 1,4-dioxane / 0.17 h / 130 °C / Inert atmosphere; Microwave irradiation 3: water; sodium hydroxide / methanol / 0.5 h / 50 °C

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2014/22528, 2014, A1
[2]Current Patent Assignee: MERCK & CO INC - WO2014/19186, 2014, A1

7
[ 1544739-25-4 ]
[ 1544739-59-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: silver carbonate / toluene / 110 °C / Inert atmosphere 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / tetrahydrofuran; water / 0.5 h / 100 °C / Microwave irradiation
	Multi-step reaction with 2 steps 1: silver carbonate / toluene / 110 °C / Inert atmosphere 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / tetrahydrofuran; water / 0.5 h / 100 °C / Microwave irradiation

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2014/22528, 2014, A1
[2]Current Patent Assignee: MERCK & CO INC - WO2014/19186, 2014, A1

8
[ 1544739-25-4 ]
[ 1544739-56-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: silver carbonate / toluene / 110 °C / Inert atmosphere 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / tetrahydrofuran; water / 0.5 h / 100 °C / Microwave irradiation 3: water; lithium hydroxide / methanol / 1 h / 20 °C
	Multi-step reaction with 3 steps 1: silver carbonate / toluene / 110 °C / Inert atmosphere 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / tetrahydrofuran; water / 0.5 h / 100 °C / Microwave irradiation 3: water; lithium hydroxide / methanol / 1 h / 20 °C

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2014/22528, 2014, A1
[2]Current Patent Assignee: MERCK & CO INC - WO2014/19186, 2014, A1

9
[ 1544739-25-4 ]
[ 1544739-68-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: silver carbonate / toluene / 110 °C / Inert atmosphere 2: potassium carbonate; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; tricyclohexylphosphine / water; 1,4-dioxane / 1 h / Reflux
	Multi-step reaction with 2 steps 1: silver carbonate / toluene / 110 °C / Inert atmosphere 2: potassium carbonate; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; tricyclohexylphosphine / water; 1,4-dioxane / 1 h / Reflux

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2014/22528, 2014, A1
[2]Current Patent Assignee: MERCK & CO INC - WO2014/19186, 2014, A1

10
[ 1544739-25-4 ]
[ 1544739-61-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: silver carbonate / toluene / 110 °C / Inert atmosphere 2: potassium carbonate; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; tricyclohexylphosphine / water; 1,4-dioxane / 1 h / Reflux 3: lithium hydroxide monohydrate; water / methanol / 2 h / 40 °C
	Multi-step reaction with 3 steps 1: silver carbonate / toluene / 110 °C / Inert atmosphere 2: potassium carbonate; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; tricyclohexylphosphine / water; 1,4-dioxane / 1 h / Reflux 3: water; lithium hydroxide monohydrate / methanol / 2 h / 40 °C

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2014/22528, 2014, A1
[2]Current Patent Assignee: MERCK & CO INC - WO2014/19186, 2014, A1

11
[ 1544739-25-4 ]
[ 1544739-74-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: silver carbonate / toluene / 110 °C / Inert atmosphere 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / tetrahydrofuran; water / 0.17 h / 100 °C / Inert atmosphere; Sealed tube; Microwave irradiation
	Multi-step reaction with 2 steps 1: silver carbonate / toluene / 110 °C / Inert atmosphere 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / tetrahydrofuran; water / 0.17 h / 100 °C / Inert atmosphere; Sealed tube; Microwave irradiation

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2014/22528, 2014, A1
[2]Current Patent Assignee: MERCK & CO INC - WO2014/19186, 2014, A1

12
[ 1544739-25-4 ]
[ 1544739-71-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: silver carbonate / toluene / 110 °C / Inert atmosphere 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / tetrahydrofuran; water / 0.17 h / 100 °C / Inert atmosphere; Sealed tube; Microwave irradiation 3: lithium hydroxide monohydrate; water / tetrahydrofuran; methanol / 4 h / 20 °C
	Multi-step reaction with 3 steps 1: silver carbonate / toluene / 110 °C / Inert atmosphere 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / tetrahydrofuran; water / 0.17 h / 100 °C / Inert atmosphere; Sealed tube; Microwave irradiation 3: water; lithium hydroxide monohydrate / tetrahydrofuran; methanol / 4 h / 20 °C

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2014/22528, 2014, A1
[2]Current Patent Assignee: MERCK & CO INC - WO2014/19186, 2014, A1

13
[ 1544739-25-4 ]
[ 1544740-48-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: silver carbonate / toluene / 110 °C / Inert atmosphere 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / tetrahydrofuran; water / 2 h / 100 °C
	Multi-step reaction with 2 steps 1: silver carbonate / toluene / 110 °C / Inert atmosphere 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / tetrahydrofuran; water / 2 h / 100 °C

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2014/22528, 2014, A1
[2]Current Patent Assignee: MERCK & CO INC - WO2014/19186, 2014, A1

14
[ 1544739-25-4 ]
[ 1544740-44-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: silver carbonate / toluene / 110 °C / Inert atmosphere 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / tetrahydrofuran; water / 2 h / 100 °C 3: lithium hydroxide monohydrate; water / tetrahydrofuran; methanol / 4 h / 20 °C
	Multi-step reaction with 3 steps 1: silver carbonate / toluene / 110 °C / Inert atmosphere 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / tetrahydrofuran; water / 2 h / 100 °C 3: water; lithium hydroxide monohydrate / tetrahydrofuran; methanol / 4 h / 20 °C

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2014/22528, 2014, A1
[2]Current Patent Assignee: MERCK & CO INC - WO2014/19186, 2014, A1

15
[ 1544739-25-4 ]
[ 1544741-33-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: silver carbonate / toluene / 110 °C / Inert atmosphere 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / tetrahydrofuran; water / 0.5 h / 100 °C / Inert atmosphere; Microwave irradiation
	Multi-step reaction with 2 steps 1: silver carbonate / toluene / 110 °C / Inert atmosphere 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / tetrahydrofuran; water / 0.5 h / 100 °C / Inert atmosphere; Microwave irradiation

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2014/22528, 2014, A1
[2]Current Patent Assignee: MERCK & CO INC - WO2014/19186, 2014, A1

16
[ 1544739-25-4 ]
[ 1544740-50-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: silver carbonate / toluene / 110 °C / Inert atmosphere 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / tetrahydrofuran; water / 0.5 h / 100 °C / Inert atmosphere; Microwave irradiation 3: water; lithium hydroxide / tetrahydrofuran; methanol / 5 h / 20 °C
	Multi-step reaction with 3 steps 1: silver carbonate / toluene / 110 °C / Inert atmosphere 2: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate / tetrahydrofuran; water / 0.5 h / 100 °C / Inert atmosphere; Microwave irradiation 3: water; lithium hydroxide / tetrahydrofuran; methanol / 5 h / 20 °C

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2014/22528, 2014, A1
[2]Current Patent Assignee: MERCK & CO INC - WO2014/19186, 2014, A1

17
[ 1544739-25-4 ]
[ 1544740-80-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: silver carbonate / toluene / 110 °C / Inert atmosphere 2: dmap; copper diacetate / acetonitrile / 80 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2014/19186, 2014, A1 Current Patent Assignee: MERCK & CO INC - WO2014/22528, 2014, A1

18
[ 1544739-25-4 ]
[ 1544740-79-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: silver carbonate / toluene / 110 °C / Inert atmosphere 2: dmap; copper diacetate / acetonitrile / 80 °C / Inert atmosphere 3: sodium hydroxide; water / tetrahydrofuran; methanol / 3 h / 20 °C
	Multi-step reaction with 3 steps 1: silver carbonate / toluene / 110 °C / Inert atmosphere 2: dmap; copper diacetate / acetonitrile / 80 °C / Inert atmosphere 3: water; sodium hydroxide / tetrahydrofuran; methanol / 3 h / 20 °C

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2014/22528, 2014, A1
[2]Current Patent Assignee: MERCK & CO INC - WO2014/19186, 2014, A1

19
[ 1544739-25-4 ]
[ 1544741-16-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: silver carbonate / toluene / 110 °C / Inert atmosphere 2: sodium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / water; 1,4-dioxane / 100 °C
	Multi-step reaction with 2 steps 1: silver carbonate / toluene / 110 °C / Inert atmosphere 2: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; sodium carbonate / water; 1,4-dioxane / 100 °C

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2014/22528, 2014, A1
[2]Current Patent Assignee: MERCK & CO INC - WO2014/19186, 2014, A1

20
[ 1544739-25-4 ]
[ 1544741-12-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: silver carbonate / toluene / 110 °C / Inert atmosphere 2: sodium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / water; 1,4-dioxane / 100 °C 3: water; lithium hydroxide / tetrahydrofuran; ethanol / 20 °C
	Multi-step reaction with 3 steps 1: silver carbonate / toluene / 110 °C / Inert atmosphere 2: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; sodium carbonate / water; 1,4-dioxane / 100 °C 3: water; lithium hydroxide / tetrahydrofuran; ethanol / 20 °C

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2014/22528, 2014, A1
[2]Current Patent Assignee: MERCK & CO INC - WO2014/19186, 2014, A1

21
[ 1544739-25-4 ]
[ 1544740-41-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: silver carbonate / toluene / 110 °C / Inert atmosphere 2: tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate / 100 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2014/19186, 2014, A1

22
[ 1544739-25-4 ]
[ 1544740-38-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: silver carbonate / toluene / 110 °C / Inert atmosphere 2: tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate / 100 °C / Inert atmosphere 3: water; sodium hydroxide / methanol / 2 h / 20 °C

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2014/19186, 2014, A1

23
[ 1544739-25-4 ]
[ 1544739-36-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: silver carbonate / toluene / 110 °C / Inert atmosphere 2: potassium carbonate; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; tricyclohexylphosphine / water; 1,4-dioxane / 0.17 h / 100 °C / Inert atmosphere; Microwave irradiation

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2014/19186, 2014, A1

24
[ 1544739-25-4 ]
[ 1544739-35-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: silver carbonate / toluene / 110 °C / Inert atmosphere 2: potassium carbonate; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; tricyclohexylphosphine / water; 1,4-dioxane / 0.17 h / 100 °C / Inert atmosphere; Microwave irradiation 3: water; lithium hydroxide / methanol / 20 °C

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2014/19186, 2014, A1

25
[ 1149378-99-3 ]
[ 1544739-25-4 ]
(1S,1aS,6aR)-4-[2-fluoro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)benzyloxy]-1,1a,6,6a-tetrahydrocyclopropa[a]indene-1-carboxylic acid ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate In N,N-dimethyl-formamide at 20℃; Inert atmosphere;	55.B Step B. (l SJaS,6aR -4-((2-fluoro-5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl benzyl oxy - l, la,6,6a-tetrahydrocvcloproparalindene-l -carboxylic acid, ethyl ester Step B. (l SJaS,6aR -4-((2-fluoro-5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl benzyl oxy - l, la,6,6a-tetrahydrocvcloproparalindene-l -carboxylic acid, ethyl ester Under a dry nitrogen atmosphere, cesium carbonate (82 mg, 0.252 mmol) was added to a solution of (lS, laS,6aR)-4-hydroxy-l,la,6,6a-tetrahydrocyclopropa[a]indene-l-carboxylic acid, ethyl ester from Reference Example 1(55 mg, 0.252 mmol) and 2-(3-(bromomethyl)-4- fluorophenyl)-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (78 mg, 0.248 mmol) in DMF (1 ml) under N2 at RT. After stirring at RT overnight, the reaction mixture was quenched by addition of saturated NH4CI solution and extracted with EtOAc (3x). The combined organic phase was washed with water (3x) and brine, dried (MgS04), filtered and the solvent evaporated. The residue was purified by preparative HPLC on silica gel eluted with hexane and EtOAc to give the title compound. MS m/e: (M+Na+) 475 and (M+H)+ 453.

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2015/89809, 2015, A1 Location in patent: Page/Page column 96 Current Patent Assignee: MERCK & CO INC - WO2015/95256, 2015, A1 Location in patent: Page/Page column 96

26
[ 1544739-25-4 ]
(1S,1aS,6aR)-4-[(2-fluoro-5-{4-methyl-6-[3-(methylsulfonyl)propoxy]pyridin-3-yl}benzyl)oxy]-1,1a,6,6a-tetrahydrocyclopropa[a]indene-1-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: caesium carbonate / N,N-dimethyl-formamide / 20 °C / Inert atmosphere 2: potassium carbonate; tetrakis(triphenylphosphine) palladium⁽⁰⁾ / water; 1,4-dioxane / 5 h / 100 °C / Sealed tube; Inert atmosphere