[ CAS No. 269410-26-6 ] {[proInfo.proName]}

Name: 269410-26-6|4,4,5,5-Tetramethyl-2-(4-phenoxyphenyl)-1,3,2-dioxaborolane|97%
Brand: Ambeed
SKU: A117971
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Quality Control of [ 269410-26-6 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 269410-26-6 ]

Product Details of [ 269410-26-6 ]

CAS No. :	269410-26-6	MDL No. :	MFCD06795691
Formula :	C₁₈H₂₁BO₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	SFCRPRMZQXUXOG-UHFFFAOYSA-N
M.W :	296.17	Pubchem ID :	17750275
Synonyms :

Calculated chemistry of [ 269410-26-6 ]

Physicochemical Properties

Num. heavy atoms :	22
Num. arom. heavy atoms :	12
Fraction Csp3 :	0.33
Num. rotatable bonds :	3
Num. H-bond acceptors :	3.0
Num. H-bond donors :	0.0
Molar Refractivity :	89.43
TPSA :	27.69 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	Yes
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	Yes
CYP3A4 inhibitor :	Yes
Log Kp (skin permeation) :	-4.95 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	4.44
Log Po/w (WLOGP) :	3.78
Log Po/w (MLOGP) :	2.66
Log Po/w (SILICOS-IT) :	2.98
Consensus Log Po/w :	2.77

Druglikeness

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

Water Solubility

Log S (ESOL) :	-4.68
Solubility :	0.0062 mg/ml ; 0.0000209 mol/l
Class :	Moderately soluble
Log S (Ali) :	-4.74
Solubility :	0.00539 mg/ml ; 0.0000182 mol/l
Class :	Moderately soluble
Log S (SILICOS-IT) :	-6.24
Solubility :	0.000169 mg/ml ; 0.00000057 mol/l
Class :	Poorly soluble

Medicinal Chemistry

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

Safety of [ 269410-26-6 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 269410-26-6 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 269410-26-6 ]
Downstream synthetic route of [ 269410-26-6 ]

[ 269410-26-6 ] Synthesis Path-Upstream 1~14

1
[ 101-55-3 ]
[ 61676-62-8 ]
[ 269410-26-6 ]

Yield	Reaction Conditions	Operation in experiment
72%	With n-butyllithium In tetrahydrofuran at -78 - -40℃; for 18 h; Inert atmosphere	4-bromodiphenyl ether(6.2g, 25.0mmol) Isopropanol pinacol borate (10.3 mL, 50 mmol)Soluble in dry tetrahydrofuran,Cooled to -78°C under nitrogen protection.n-Butyllithium (2.5M, 18 mL, 45 mmol) was added dropwise,After completion of the addition, the mixture was stirred for 6 hours and slowly warmed to -40°C for 12 hours.The reaction was added to saturated ammonium chloride solution and extracted three times with ethyl acetate.The organic phases were combined and dried over anhydrous sodium sulfate.It was evaporated to dryness by rotary evaporation and purified by column to give 5.4 g of the target compound in a yield of 72percent.

Reference： [1] Patent: CN107759602, 2018, A, . Location in patent: Paragraph 0180-0182

2
[ 101-55-3 ]
[ 25015-63-8 ]
[ 269410-26-6 ]

Reference： [1] Patent: US6680401, 2004, B1, . Location in patent: Page column 69

3
[ 330-84-7 ]
[ 73183-34-3 ]
[ 269410-26-6 ]
[ 99770-93-1 ]

Reference： [1] ACS Catalysis, 2017, vol. 7, # 7, p. 4535 - 4541

4
[ 76-09-5 ]
[ 269410-26-6 ]

Reference： [1] Tetrahedron Letters, 2013, vol. 54, # 2, p. 166 - 169

5
[ 1374791-08-8 ]
[ 73183-34-3 ]
[ 269410-26-6 ]

Reference： [1] Journal of the American Chemical Society, 2015, vol. 137, # 4, p. 1593 - 1600

6
[ 73183-34-3 ]
[ 269410-26-6 ]

Reference： [1] Chemical Communications, 2015, vol. 51, # 74, p. 14068 - 14071

7
[ 101-55-3 ]
[ 73183-34-3 ]
[ 269410-26-6 ]

Reference： [1] Advanced Synthesis and Catalysis, 2016, vol. 358, # 6, p. 977 - 983
[2] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 24, p. 7543 - 7546

8
[ 101-55-3 ]
[ 269410-26-6 ]

Reference： [1] Tetrahedron Letters, 2013, vol. 54, # 2, p. 166 - 169

9
[ 831-82-3 ]
[ 269410-26-6 ]

Reference： [1] Journal of the American Chemical Society, 2015, vol. 137, # 4, p. 1593 - 1600

10
[ 101-84-8 ]
[ 269410-26-6 ]

Reference： [1] Chemical Communications, 2015, vol. 51, # 74, p. 14068 - 14071

11
[ 76-09-5 ]
[ 51067-38-0 ]
[ 269410-26-6 ]

Reference： [1] Bulletin of the Chemical Society of Japan, 2009, vol. 82, # 7, p. 870 - 878

12
[ 101-84-8 ]
[ 25015-63-8 ]
[ 269410-26-6 ]
[ 864772-18-9 ]

Reference： [1] Organic and Biomolecular Chemistry, 2015, vol. 13, # 41, p. 10336 - 10340

13
[ 101-84-8 ]
[ 25015-63-8 ]
[ 269410-26-6 ]
[ 864772-18-9 ]

Reference： [1] Organic and Biomolecular Chemistry, 2015, vol. 13, # 41, p. 10336 - 10340

14
[ 269410-26-6 ]
[ 1022150-11-3 ]

Reference： [1] Patent: CN107759602, 2018, A,

[ 269410-26-6 ] Synthesis Path-Downstream 1~67

1
[ 101-55-3 ]
[ 25015-63-8 ]
[ 269410-26-6 ]

Yield	Reaction Conditions	Operation in experiment
		[00432] In a reaction tube under nitrogen, a mixture of PdCl2(dppf)CH2Cl2 (22 mg; 0.027 mmol) and triethylamine (0.36 ml; 2.58 mmol) in dioxane (4 ml; dried over 4 ? sieves) was sealed and stirred at 80 C. overnight (18 h). After cooling to room temperature, HB(pin) (0.19 ml;, 1.31 mmol) and 4-bromodiphenyl ether (216 mg; 0.865 mmol) were added and the reaction mixture was stirred at 80 C. GC analysis after 18 h showed a peak at 13.84 mins which was identified by GC/MS as the desired compound.

Reference： [1]Patent: US6680401,2004,B1 .Location in patent: Page column 69

2
[ 269410-26-6 ]
[ 1187951-46-7 ]
[ 1187951-67-2 ]

Reference： [1]Bulletin of the Chemical Society of Japan,2009,vol. 82,p. 870 - 878

3
[ 269410-26-6 ]
[ 1187951-53-6 ]
[ 1187951-71-8 ]

Reference： [1]Bulletin of the Chemical Society of Japan,2009,vol. 82,p. 870 - 878

4
[ 76-09-5 ]
[ 51067-38-0 ]
[ 269410-26-6 ]

Reference： [1]Angewandte Chemie - International Edition,2019,vol. 58,p. 6549 - 6553
Angew. Chem.,2019,vol. 131,p. 6621 - 6625,5
[2]Bulletin of the Chemical Society of Japan,2009,vol. 82,p. 870 - 878

5
[ 269410-26-6 ]
[ 1152617-11-2 ]
[ 1152616-18-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 175 - 179

6
[ 269410-26-6 ]
potassium (trifluoromethyl)trimethoxyborate [ No CAS ]
[ 2367-02-4 ]

Reference： [1]Chemistry - A European Journal,2012,vol. 18,p. 1577 - 1581

7
[ 101-55-3 ]
[ 269410-26-6 ]

Reference： [1]Tetrahedron Letters,2013,vol. 54,p. 166 - 169

8
[ 76-09-5 ]
C₁₈H₁₃BO₃ [ No CAS ]
[ 269410-26-6 ]

Yield	Reaction Conditions	Operation in experiment
	In dimethyl sulfoxide; at 20℃; for 0.5h;	General procedure: General procedure: The synthetic procedure for pentafluorophenyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzenesulfonate (a) is presented as an example (Scheme 1). 2,2'-Bis(1,3,2-benzodioxaborole) (cat2B2, 262 mg, 1.10 mmol), PdCl2(dppf) (25 mg, 0.030 mmol), AcOK (294 mg, 3.0 mmol), pentafluorophenyl 4-bromobenzenesulfonate (403 mg, 1.0 mmol), and EtOH (6.0 mL) were charged in a reaction vessel under an Ar atmosphere. The resulting mixture was stirred for 2 h at 80 C. After cooling to room temperature, pinacol (260 mg, 2.20 mmol) was added to the mixture. The mixture was further stirred for 30 min at room temperature. H2O and n-hexane were added to the mixture and the product was extracted into the organic layer. After drying the organic layer with anhydrous MgSO4, solids were removed by filtration. The filtrate was concentrated. The product was obtained as a white solid by Kugelrohr distillation.

Reference： [1]Tetrahedron Letters,2013,vol. 54,p. 166 - 169

9
[ 101-55-3 ]
[ 73183-34-3 ]
[ 269410-26-6 ]

Reference： [1]Advanced Synthesis and Catalysis,2016,vol. 358,p. 977 - 983
[2]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 7543 - 7546

10
[ 269410-26-6 ]
[ 1194-21-4 ]
[ 1415309-83-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 7543 - 7546

11
[ 269410-26-6 ]
[ 27126-76-7 ]
[ 1417418-04-2 ]

Reference： [1]Angewandte Chemie - International Edition,2012,vol. 51,p. 12555 - 12558
Angew. Chem.,2012,vol. 124,p. 12723 - 12726,4

12
[ 269410-26-6 ]
[ 1418272-79-3 ]
[ 1418272-80-6 ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 60 - 90℃;	b) tert-butyl 6-(4-amino-3-(4-phenoxyphenyl)-lH-pyrazolo[3.4-dlpyrimidin-l-yl)-1.4-oxazepane-4- carboxylate tert-butyl 6-(4-amino-3-iodo-lH-pyrazolo[3,4-d]pyrimidin-l-yl)-l,4-oxazepane-4-carboxylate (1.18 mmol) is dissolved in ethylene glycol dimethylether (50 mL) and water (10 mL). 4,4,5,5- tetramethyl-2-(4-phenoxyphenyl)-l,3,2-dioxaborolane (1.47 mmol), palladium tetrakistriphenylphosphine (0.059 mmol) and sodium carbonate (2.95 mmol) are added and the reaction is heated for 12-20 hours. Additional boronate and palladium tetrakistriphenylphosphine are added and the reaction is heated at 60- 90 C for a further 20-24 hours. The reaction is concentrated under reduced pressure. The remaining residue was partitioned between dichloromethane and water. The organic layer is dried then concentrated under reduced pressure to yield the title comound.

Reference： [1]Patent: WO2013/10136,2013,A2 .Location in patent: Paragraph 00371

13
[ 269410-26-6 ]
[ 13162-26-0 ]
[ 1497436-17-5 ]

Reference： [1]Journal of Heterocyclic Chemistry,2013,vol. 50,p. 1395 - 1399

14
[ 1374791-08-8 ]
[ 73183-34-3 ]
[ 269410-26-6 ]

Reference： [1]Journal of the American Chemical Society,2015,vol. 137,p. 1593 - 1600
[2]Organic Letters,2020

15
[ 831-82-3 ]
[ 269410-26-6 ]

Reference： [1]Journal of the American Chemical Society,2015,vol. 137,p. 1593 - 1600

16
[ 269410-26-6 ]
[ 330792-72-8 ]
[ 330786-13-5 ]

Yield	Reaction Conditions	Operation in experiment
0.7 g	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; ethanol; at 80℃; for 36h;Inert atmosphere;	4,4,5,5-Tetramethyl-2-(4-phenoxyphenyl)-1,3,2-dioxaborolane (1.0 g, 3.38 mmol) was dissolved in ethylene glycol dimethyl ether (38 mL) and ethanol (11 mL), and 4-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexanone (0.5 g, 1.35 mmol), a saturated sodium carbonate solution (12 mL), and tetrakis(triphenylphosphine)palladium (0.1 g, 0.10 mmol) were sequentially added to the solution. The mixture was stirred all night and half a day in an argon atmosphere at 80C. After the mixture was left to cool naturally, the mixture was extracted by adding dichloromethane thereto, and the extract was partitioned and washed with saturated brine. The organic layer was dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. An oily substance thus obtained was purified by silica gel column chromatography (dichloromethane/methanol = 10/1 ? dichloromethane/methanol = 95/5), and thus 4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)cyclohexanone (0.7 g) was obtained.

Reference： [1]Patent: EP2878601,2015,A1 .Location in patent: Paragraph 0190; 0357

17
[ 364355-46-4 ]
[ 269410-26-6 ]
tert-butyl 4-(4-chloro-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.6 g	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 80℃;	tert-Butyl 4-(4-chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)piperidine-1-carboxylate (0.7 g, 1.49 mmol) and <strong>[269410-26-6]<strong>[269410-26-6]4,4,5,5-tetramethyl-2-(4-phenoxyphenyl)-1,3,2-dioxaborolan</strong>e</strong> (0.5 mg, 1.79 mmol) were dissolved in ethylene glycol dimethyl ether (25 mL), and a saturated aqueous solution of sodium carbonate (5 mL) and tetrakis(triphenylphosphine)palladium (0.1 g, 0.10 mmol) were sequentially added thereto. The mixture was stirred overnight at 80C. After the mixture was left to cool naturally, water was added thereto, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue thus obtained was purified by silica gel column chromatography (hexane/ethyl acetate = 3/1), and thus the title compound (yellow solid, 0.6 g) was obtained.

Reference： [1]Patent: EP2878601,2015,A1 .Location in patent: Paragraph 0178

18
[ 269410-26-6 ]
[ 262444-48-4 ]
[ 490030-16-5 ]

Yield	Reaction Conditions	Operation in experiment
5.22 g	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 80℃; for 3.5h;	4-Phenoxyphenylboronic acid pinacol ester (8.44 g) was dissolved in ethylene glycol dimethyl ether (300 mL), and 4-chloro-7-(1,4-dioxaspiro[4.5]decan-8-yl)-5-iodo-7H-pyrrolo[2,3-d]pyrimidine (7.97 g), sodium carbonate (6.02 g), water (200 mL) and tetrakis(triphenylphosphine)palladium (1.32 g) were sequentially added to the solution. The mixture was stirred at 80C for 3.5 hours. The mixture was left to cool naturally, subsequently ethyl acetate (400 mL) was added thereto, and the mixture was partitioned. The organic layer was washed with water (250 mL) and saturated brine (250 mL) and dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. A pale brown oily substance (13.8 g) was obtained, and hexane/ethyl acetate (5 : 1, 40 mL) and dichloromethane (15 mL) were added thereto. A white solid precipitated therefrom was collected by filtration and dried, and thus 4-chloro-5-(4-phenoxyphenyl)-7-(1,4-dioxaspiro[4.5]decan-8-yl)-7H-pyrrolo[2,3-d]pyrimidin e (5.22 g) was obtained.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 4994 - 4998
[2]Patent: EP2878601,2015,A1 .Location in patent: Paragraph 0155

19
[ 101-84-8 ]
[ 25015-63-8 ]
[ 269410-26-6 ]
[ 864772-18-9 ]

Reference： [1]Organic and Biomolecular Chemistry,2015,vol. 13,p. 10336 - 10340

20
[ 269410-26-6 ]
[ 2519-16-6 ]

Reference： [1]Chemical Communications,2015,vol. 51,p. 14068 - 14071

21
bis(4-phenoxyphenyl)iodonium acetate [ No CAS ]
[ 73183-34-3 ]
[ 269410-26-6 ]

Reference： [1]Chemical Communications,2015,vol. 51,p. 14068 - 14071

22
bis(4-phenoxyphenyl)iodonium 4-methylbenzenesulfonate [ No CAS ]
[ 269410-26-6 ]

Reference： [1]Chemical Communications,2015,vol. 51,p. 14068 - 14071

23
bis(4-phenoxyphenyl)iodonium chloride [ No CAS ]
[ 269410-26-6 ]

Reference： [1]Chemical Communications,2015,vol. 51,p. 14068 - 14071

24
[ 101-84-8 ]
[ 269410-26-6 ]

Reference： [1]Chemical Communications,2015,vol. 51,p. 14068 - 14071
[2]Science China Chemistry,2020,vol. 63,p. 336 - 340

25
[ 269410-26-6 ]
(S)-methyl 1-(8-amino-1-bromoimidazo[1,5-a]pyrazin-3-yl)piperidine-3-carboxylate [ No CAS ]
(S)-1-(8-amino-1-(4-phenoxyphenyl)imidazo[1,5-a]pyrazin-3-yl)piperidine-3-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; at 100℃; for 1h;	A solution of (S)-methyl l-(8-amino-l-bromoimidazo[l,5-a]pyrazin-3- yl)piperidine-3-carboxylate (80 mg, 0.15 mmol) and 4,4,5, 5-tetramethyl-2-(4-phenoxyphenyl)- 1,3,2-dioxaborolane (65.5 mg, 0.3 mmol) in dioxane (1.5 mL) was added a solution of K2CO3(95.2mg,0.6 mmol ), pd(dppf)Cl2 (10.35 mg, 0.014mmol), then the mixture was heated at 100 C for lhour. After the raction,the mixture was cooled to room temperature and purified by pre-HPLC to give (S)-l-(8-amino-l-(4-phenoxyphenyl)imidazo[l,5-a]pyrazin-3-yl)piperidine-3- carboxylic acid . 1HNMR (400MHz, CDC13): delta= 13.79 (br. s., IH), 11.22 (br. s., IH), 8.26 - 8.15 (m, IH), 7.56 (d, J=8.5 Hz, 2H), 7.41 (t, J=7.5 Hz, 2H), 7.27 (s, IH), 7.21 (d, J=7.5 Hz, IH), 7.11 (dd, J=8.0, 16.1 Hz, 4H), 6.11 (br. s., IH), 4.00 - 3.88 (m, IH), 3.57 (d, J=l 1.5 Hz, IH), 3.24 (br. s., IH), 3.01 - 2.93 (m, IH), 2.85 (br. s., IH), 2.48 (d, J=11.5 Hz, IH), 1.77 (br. s., IH), 1.37 - 1.19 (m, IH) ppm. MS (ESI): M/Z (M+l)+= 429.5.

Reference： [1]Patent: WO2016/109219,2016,A1 .Location in patent: Page/Page column 63-64

26
[ 269410-26-6 ]
[ 38078-09-0 ]
C₁₆H₁₉NO₂S [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2016,vol. 55,p. 10811 - 10815
Angew. Chem.,2016,vol. 128,p. 10969 - 10973,5

27
[ 269410-26-6 ]
[ 51010-74-3 ]
C₁₆H₁₇NO₃S [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2016,vol. 55,p. 10811 - 10815
Angew. Chem.,2016,vol. 128,p. 10969 - 10973,5

28
[ 269410-26-6 ]
tert-butyl 2-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)morpholinyl-4-carboxylate [ No CAS ]
tert-butyl 2-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)morpholin-4-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With bis-triphenylphosphine-palladium(II) chloride; caesium carbonate; In N,N-dimethyl-formamide; at 90℃;	Weigh 220 mg of the compound prepared in Step 1 tert-butyl 2-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)morpholinyl-4-carboxylate In a reaction flask, After adding 10 ml of DMF, 296 mg of <strong>[269410-26-6]4-phenoxybenzeneboronic acid pinacol ester</strong> was added, 17mg of bis(triphenylphosphine)palladium dichloride, 326 mg of cesium carbonate (Cs2C03), After stirring at 90 C until the reaction is complete,Add water to quench, Ethyl acetate extraction, dry, filter, concentrate, Column chromatography, The title compound was obtained.

Reference： [1]Patent: CN105461720,2016,A .Location in patent: Paragraph 0089; 0090; 0091

29
[ 269410-26-6 ]
(S)-6-(8-amino-1-bromoimidazo[1,5-a]pyrazin-3-yl)-5-azaspiro[2.4]heptane-5-carboxylic acid tert-butyl ester [ No CAS ]
C₂₉H₃₁N₅O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
865.6 mg	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; ethanol; water; at 90℃; for 3h;Inert atmosphere;	Under nitrogen protection,To a solution of (S) -6- (8-amino-1-bromoimidazo [1,5-a] pyrazin-3-yl) -5-azaspiro [2.4] Ester (1 g, 2.45 mmol),4,4,5,5-tetramethyl-2- (4-phenoxyphenyl) -1,3,2-dioxaborolane (796.7 mg, 2.69 mmol)Na2CO3 (519.4 mg, 4.9 mmol)Of dioxane / EtOH / water (12 mL / 4 mL / 4 mL)In the mixed solution,Pd (PPh3) 4 (141.56 mg, 0.1225 mmol) was added,The reaction mixture was stirred for 3h at 90 ,TLC shows the raw material reaction is complete,The reaction solution was quenched by the addition of water,Extracted with EA (10 mL x 3)Organic phase with saturated salt water backwash,Anhydrous Na2SO4 dried,After evaporation in vacuo, the residue was purified by column chromatography (DCM / MeOH = 60/1 to 30/1)To give 865.6 mg of the title compound

Reference： [1]Patent: CN106831787,2017,A .Location in patent: Paragraph 0329; 0330; 0331; 0332

30
[ 269410-26-6 ]
[ 330793-99-2 ]
[ 1418272-69-1 ]

Reference： [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 8407 - 8424

31
[ 269410-26-6 ]
[ 73183-34-3 ]
[ 99770-93-1 ]

Reference： [1]ACS Catalysis,2017,vol. 7,p. 4535 - 4541

32
[ 330-84-7 ]
[ 73183-34-3 ]
[ 269410-26-6 ]
[ 99770-93-1 ]

Reference： [1]ACS Catalysis,2017,vol. 7,p. 4535 - 4541

33
[ 101-55-3 ]
[ 61676-62-8 ]
[ 269410-26-6 ]

Yield	Reaction Conditions	Operation in experiment
72%	With n-butyllithium; In tetrahydrofuran; at -78 - -40℃; for 18h;Inert atmosphere;	4-bromodiphenyl ether(6.2g, 25.0mmol) Isopropanol pinacol borate (10.3 mL, 50 mmol)Soluble in dry tetrahydrofuran,Cooled to -78C under nitrogen protection.n-Butyllithium (2.5M, 18 mL, 45 mmol) was added dropwise,After completion of the addition, the mixture was stirred for 6 hours and slowly warmed to -40C for 12 hours.The reaction was added to saturated ammonium chloride solution and extracted three times with ethyl acetate.The organic phases were combined and dried over anhydrous sodium sulfate.It was evaporated to dryness by rotary evaporation and purified by column to give 5.4 g of the target compound in a yield of 72%.

Reference： [1]Patent: CN107759602,2018,A .Location in patent: Paragraph 0180-0182

34
[ 269410-26-6 ]
[ 1022150-11-3 ]