[ CAS No. 27329-70-0 ] {[proInfo.proName]}

Name: 27329-70-0|(5-Formylfuran-2-yl)boronic acid|97%
Brand: Ambeed
SKU: A184848
Price: 11.0 USD
Availability: InStock
Rating: 90 (35 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 27329-70-0 * 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 [ 27329-70-0 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 27329-70-0 ]

SDS Specification

Alternatived Products of [ 27329-70-0 ]

Product Details of [ 27329-70-0 ]

CAS No. :	27329-70-0	MDL No. :	MFCD01114696
Formula :	C₅H₅BO₄	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	JUWYQISLQJRRNT-UHFFFAOYSA-N
M.W :	139.90	Pubchem ID :	2734355
Synonyms :

Calculated chemistry of [ 27329-70-0 ]

Physicochemical Properties

Num. heavy atoms :	10
Num. arom. heavy atoms :	5
Fraction Csp3 :	0.0
Num. rotatable bonds :	2
Num. H-bond acceptors :	4.0
Num. H-bond donors :	2.0
Molar Refractivity :	33.92
TPSA :	70.67 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-7.35 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	-0.28
Log Po/w (WLOGP) :	-1.23
Log Po/w (MLOGP) :	-2.29
Log Po/w (SILICOS-IT) :	-1.09
Consensus Log Po/w :	-0.98

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-0.77
Solubility :	23.8 mg/ml ; 0.17 mol/l
Class :	Very soluble
Log S (Ali) :	-0.74
Solubility :	25.2 mg/ml ; 0.18 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-0.42
Solubility :	52.8 mg/ml ; 0.378 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.56

Safety of [ 27329-70-0 ]

Signal Word:	Danger	Class:	9
Precautionary Statements:	P261-P264-P271-P280-P302+P352-P304+P340-P305+P351+P338-P310-P362+P364-P403+P233-P501	UN#:	3077
Hazard Statements:	H315-H318-H335-H411	Packing Group:	Ⅲ
GHS Pictogram:

Application In Synthesis of [ 27329-70-0 ]

* 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 [ 27329-70-0 ]
Downstream synthetic route of [ 27329-70-0 ]

[ 27329-70-0 ] Synthesis Path-Upstream 1~13

1
[ 27329-70-0 ]
[ 52938-97-3 ]

Reference： [1] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 21, p. 6384 - 6393,10

2
[ 637-87-6 ]
[ 27329-70-0 ]
[ 34035-03-5 ]

Yield	Reaction Conditions	Operation in experiment
95%	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In 1,2-dimethoxyethane; ethanol; water at 65℃; for 1 h;	General procedure: 1.00 mmol arylhalide, 1.30 mmol furfural-boronic acid and 0.05 mmolBis(triphenylphosphine)palladium(II) dichloride were treated with 0.30 mLdimethoxyethane, 0.50 mL ethanol and 0.30 mL aqueous 2M sodium carbonate solution.The reaction was heated to 65°C for 1h or until the TLC showed no remaining startingmaterial. The mixture was evaporated and extracted three times with ethyl acetate. Thecombined organic layers were washed with brine, dried over MgSO4, filtered andconcentrated. The crude product was purified by column chromatography usinghexanes/ethyl acetate (9:1).

Reference： [1] European Journal of Medicinal Chemistry, 2017, vol. 126, p. 929 - 936
[2] Chemical Biology and Drug Design, 2017, vol. 89, # 4, p. 585 - 598

3
[ 106-39-8 ]
[ 27329-70-0 ]
[ 34035-03-5 ]

Yield	Reaction Conditions	Operation in experiment
63%	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In 1,2-dimethoxyethane; ethanol; water at 60℃; for 2 h;	General procedure: To a solution of 1-bromo-4-chlorobenzene (478 mg, 2.50 mmol) in a mixture of DME (7.5 mL) and EtOH (5.0 mL) were added PdCl₂(PPh₃)₂ (36.5 mg, 52.0 μmol), 5-formyl-2-furanboronic acid (365 mg, 2.61 mmol), and 2 M aqueous Na₂CO₃ solution. The reaction mixture was stirred for 2 h at 60 °C, then cooled to room temperature, and volatile materials were removed under reduced pressure. To the obtained residue was added H₂O and the resulting mixture was extracted with EtOAc. The organic layer was washed with brine, dried over MgSO₄, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/EtOAc = 5:1) to afford 19e (323 mg, 63percent) as a yellow solid. ¹H NMR (500 MHz, CDCl₃) δ 9.64 (1H, s), 7.73 (2H, d, J = 8.5 Hz), 7.40 (2H, d, J = 8.5 Hz), 7.30 (1H, d, J = 3.6 Hz), 6.81 (1H, d, J = 3.6 Hz); MS (FAB) m/z 207 (M+H)⁺.

Reference： [1] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 21, p. 6384 - 6393,10
[2] Organic and Biomolecular Chemistry, 2012, vol. 10, # 36, p. 7402 - 7417

4
[ 27329-70-0 ]
[ 586-78-7 ]
[ 7147-77-5 ]

Reference： [1] Organic and Biomolecular Chemistry, 2012, vol. 10, # 36, p. 7402 - 7417

5
[ 636-98-6 ]
[ 27329-70-0 ]
[ 7147-77-5 ]

Reference： [1] Chemical Biology and Drug Design, 2017, vol. 89, # 4, p. 585 - 598
[2] Chemical Biology and Drug Design, 2018, vol. 91, # 1, p. 257 - 268

6
[ 27329-70-0 ]
[ 589-87-7 ]
[ 20005-42-9 ]

Yield	Reaction Conditions	Operation in experiment
85%	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In 1,2-dimethoxyethane; ethanol; water at 65℃; for 1 h;	General procedure: 1.00 mmol arylhalide, 1.30 mmol furfural-boronic acid and 0.05 mmolBis(triphenylphosphine)palladium(II) dichloride were treated with 0.30 mLdimethoxyethane, 0.50 mL ethanol and 0.30 mL aqueous 2M sodium carbonate solution.The reaction was heated to 65°C for 1h or until the TLC showed no remaining startingmaterial. The mixture was evaporated and extracted three times with ethyl acetate. Thecombined organic layers were washed with brine, dried over MgSO4, filtered andconcentrated. The crude product was purified by column chromatography usinghexanes/ethyl acetate (9:1).
68%	Stage #1: With bis-triphenylphosphine-palladium(II) chloride In 1,2-dimethoxyethane; ethanol for 0.5 h; Stage #2: With sodium carbonate In 1,2-dimethoxyethane; ethanol; water for 12 h; Reflux	General procedure: Method A: To a solution of 3a (150 mg, 0.47 mmol) in a mixture of dry DME (3 mL) and dry EtOH (3 mL), bis(triphenylphosphine)palladium(II) dichloride (17 mg, 0.02 mmol) was added. After 30 min, a solution of sodium carbonate (299 mg, 2.82 mmol) in H2O(2 mL) and a solution of 5-formyl-2-furanylboronic acid 4 (93 mg,0.66 mmol) in dry EtOH (1.5 mL) were added in this order. The reaction was heated under reflux for 12 h. After this time, H2O (4 mL)was added at 25 C and the organic phase was extracted with EtOAc(3 5 mL), dried over sodium sulfate, filtered and evaporated in vacuo. The crude product was purified by flash chromatography on silica gel (2percent EtOAc in petroleum ether) to give 5a as orange solid(79 mg, 60percent). Method B: To a suspension of 16a (1.0 g, 4.8 mmol) in H2O (20 mL), HCl (37percent, 2 mL) was added. The resulting solution was cooled at 0 C and a solution of sodium nitrite (397 mg, 5.76 mmol) in H2O (2 mL) was added dropwise. After 1 h, a solution of 17(400 mL, 4.8 mmol) in acetone (2 mL) and solid copper(II) chloride(128 mg, 0.96 mmol) were added. The mixture kept at 25 C for 12 h. EtOAc was added (3 10 mL) and the organic phase was separated, dried over sodium sulfate, filtered and evaporated in vacuo. The crude product was purified by flash chromatography on silica gel (2percent EtOAc in petroleum ether) to give 5a as orange solid(1.23 g, 90percent).

Reference： [1] European Journal of Medicinal Chemistry, 2017, vol. 126, p. 929 - 936
[2] European Journal of Medicinal Chemistry, 2018, vol. 150, p. 698 - 718

7
[ 27329-70-0 ]
[ 106-37-6 ]
[ 20005-42-9 ]

Reference： [1] Organic and Biomolecular Chemistry, 2012, vol. 10, # 36, p. 7402 - 7417

8
[ 27329-70-0 ]
[ 619-44-3 ]
[ 53355-29-6 ]

Yield	Reaction Conditions	Operation in experiment
75%	With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate In 1,4-dioxane; water at 100℃; Inert atmosphere	General procedure: A mixture of substituted iodobenzene (2 mmol), (5-formylfuran-2-yl)boronic acid (420 mg, 3mmol, 1.5 equiv), Pd(Ph3P)2Cl2 (0.1 mmol, 0.05 equiv, 70 mg) and potassium carbonate (6 mmol,3 equiv, 828 mg) in dioxone/H2O (6 mL/2 mL) was stirred at 100 °C under argon atmosphereuntil the starting material was consumed (typically 20 h). The reaction mixture was then diluted with 25 mL of saturated brine. The mixture was then extracted with EtOAc (25 mL × 2), and the organic layers were combined, dried over Na2SO4. The concentrated crude product was purifie dby column chromatography to afford c2a-e. The second step is the same as procedure A.

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 6, p. 1024 - 1029
[2] Patent: CN106977474, 2017, A, . Location in patent: Paragraph 0034; 0037; 0038
[3] Chemical Biology and Drug Design, 2018, vol. 91, # 1, p. 257 - 268

9
[ 27329-70-0 ]
[ 619-42-1 ]
[ 53355-29-6 ]

Reference： [1] Bioorganic and Medicinal Chemistry, 2004, vol. 12, # 17, p. 4585 - 4600
[2] Bioorganic and Medicinal Chemistry Letters, 2003, vol. 13, # 13, p. 2159 - 2161

10
[ 13529-27-6 ]
[ 27329-70-0 ]

Yield	Reaction Conditions	Operation in experiment
75%	Stage #1: With Triisopropyl borate; lithium diisopropyl amide In tetrahydrofuran; n-heptane; ethylbenzene at -10 - 0℃; for 1 h; Stage #2: With hydrogenchloride In tetrahydrofuran; n-heptane; ethylbenzene; water at 30℃;	A dried 500 mL 3-neck flask with mechanical stirrer, internal thermometer and addition funnel under nitrogen is charged with 20,16 g (0,118 mol) furfuraldiethylacetal, 33,4 g (0,177 mol) triisopropylborate and 40 mL of anhydrous THF. The water content of the reaction mixture was measured according to the Karl-Fischer-titration method and was determined to be less than 800 μg/mL of water. The solution is cooled to an internal temperature of -10°C. Keeping the temperature at -10°C to 0°C 84 mL (25 wtpercent, 1.84 M solution THF, heptane, ethylbenzene from Chemmetal, content determined by titration, 1.3 equivalents) LDA was added via addition funnel to the reaction mixture over a period of 1 hour. Using a canula the reaction mixture was subsequently transferred to precooled aqueous hydrochloric acid which was obtained by mixing 33 mL of concentrated hydrochloric acid and 55 mL water. The reaction temperature was maintained at a temperature of less than 30°C. The resulting tan slurry of 5-formyl-2-furylboronic acid was cooled to 0°C and filtered. The filter cake was washed twice with 20 mL of cold water to give 17.6 g of wet cake. Drying (40°C, vacuum oven) gave 12.41 g of an off-white product. The overall yield of 5-formyl-2-furylboronic acid was 75percent. The content of unreacted furfural in the crude product was determined to be less than 0,1percent.

Reference： [1] Patent: EP1403271, 2004, A1, . Location in patent: Page 3, 4
[2] Organic and Biomolecular Chemistry, 2003, vol. 1, # 9, p. 1447 - 1449

11
[ 13529-27-6 ]
[ 121-43-7 ]
[ 27329-70-0 ]

Reference： [1] Patent: WO2004/24738, 2004, A1, . Location in patent: Page/Page column 13
[2] Organic and Biomolecular Chemistry, 2003, vol. 1, # 9, p. 1447 - 1449

12
[ 1708-41-4 ]
[ 27329-70-0 ]

Reference： [1] Patent: US2009/131685, 2009, A1, . Location in patent: Page/Page column 9
[2] Patent: US2009/131685, 2009, A1, . Location in patent: Page/Page column 8-9
[3] Patent: US2009/131685, 2009, A1, . Location in patent: Page/Page column 9
[4] Patent: US2009/131685, 2009, A1, . Location in patent: Page/Page column 9

13
[ 1899-24-7 ]
[ 5419-55-6 ]
[ 27329-70-0 ]

Reference： [1] Chemical Biology and Drug Design, 2017, vol. 89, # 4, p. 585 - 598

[ 27329-70-0 ] Synthesis Path-Downstream 1~88

1
[ 13195-50-1 ]
[ 27329-70-0 ]
5-(5-nitrothiophen-2-yl)-furan-2-carbaldehyde [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2003,vol. 1,p. 1447 - 1449

2
[ 13529-27-6 ]
[ 27329-70-0 ]

Yield	Reaction Conditions	Operation in experiment
75%		A dried 500 mL 3-neck flask with mechanical stirrer, internal thermometer and addition funnel under nitrogen is charged with 20,16 g (0,118 mol) furfuraldiethylacetal, 33,4 g (0,177 mol) triisopropylborate and 40 mL of anhydrous THF. The water content of the reaction mixture was measured according to the Karl-Fischer-titration method and was determined to be less than 800 mug/mL of water. The solution is cooled to an internal temperature of -10C. Keeping the temperature at -10C to 0C 84 mL (25 wt%, 1.84 M solution THF, heptane, ethylbenzene from Chemmetal, content determined by titration, 1.3 equivalents) LDA was added via addition funnel to the reaction mixture over a period of 1 hour. Using a canula the reaction mixture was subsequently transferred to precooled aqueous hydrochloric acid which was obtained by mixing 33 mL of concentrated hydrochloric acid and 55 mL water. The reaction temperature was maintained at a temperature of less than 30C. The resulting tan slurry of 5-formyl-2-furylboronic acid was cooled to 0C and filtered. The filter cake was washed twice with 20 mL of cold water to give 17.6 g of wet cake. Drying (40C, vacuum oven) gave 12.41 g of an off-white product. The overall yield of 5-formyl-2-furylboronic acid was 75%. The content of unreacted furfural in the crude product was determined to be less than 0,1%.

Reference： [1]Patent: EP1403271,2004,A1 .Location in patent: Page 3, 4
[2]Organic and Biomolecular Chemistry,2003,vol. 1,p. 1447 - 1449

3
[ 27329-70-0 ]
[ 619-42-1 ]
[ 53355-29-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 4585 - 4600
[2]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 2159 - 2161

4
[ 626-55-1 ]
[ 27329-70-0 ]
[ 38588-49-7 ]

Yield	Reaction Conditions	Operation in experiment
96%	With tetrabutylammomium bromide; potassium carbonate; In methanol; water; at 80℃; for 0.333333h;Reflux;	General procedure: A mixture of hetarylboronic acid 4a-d(1.2 mmol), aryl(hetaryl) bromide 5a-h or hetaryl chloride7a,b (1 mmol), Bu4NBr (3 mg, 1 mol %, for water-insolublearyl(hetaryl) halides 5b-g and 7a,b), and K2CO3 (346 mg,2.5 mmol) in 2 (5 ml) was heated to 80 and treated byadding 0.1-1 mol % of Pd-Ni(Co)-B-L (an aliquot of0.1 M solution of bimetallic catalyst in MeOH-H2Omixture). The reactor was fitted with a reflux condenserand placed in a hot silicone oil bath (150). The reactionmixture was vigorously stirred at reflux until completeconversion of the starting materials was achieved. Thereaction progress was controlled by TLC method (eluenthexane-Et2O, 3:1). The amount of catalyst, reactionduration and yields of the target compounds 6a-k are listedin Table 4. In the case of the activated aryl bromides5a,b,d,f, the reaction was highly exothermic, therefore aneffective reflux condenser was essential for scaling up thissynthesis.After the reaction was complete, the mixture was dilutedwith H2O (10 ml), heated to 80C, and filtered while hotthrough a Whatman autovial syringeless filter (pore size0.45 mum). The filtrate was diluted with 10-15 vol % ofEtOH, heated to ~50C, stirred, and slowly acidified with5% HCl to pH 2-3. The resulting precipitate was easy tofilter, and analytically pure products 6a,h,k were obtainedwithout chromatographic purification. In the case of thewater-insoluble heterobiaryls 6b-g,i,j, the reaction mixturewas diluted with saturated solution of NaCl (10 ml) andextracted with Et2O or EtOAc (3×5 ml). The obtainedextract was dried over anhydrous Na2SO4, filtered througha silica gel layer, and the solvent was evaporated at reducedpressure. The residues in all cases were >99% pureproducts (according to the results of elemental analysis).Analytically pure samples were obtained by recrystallizationof heterobiaryls 6a-k from a minimal amount ofaqueous EtOH (10-20% 2) or by converting amines intothe respective hydrochlorides. The residual metal content inthe isolated heterobiaryls 6a-k did not exceed 1 ppmaccording to the results of atomic absorption spectrometry.

Reference： [1]Russian Journal of General Chemistry,2014,vol. 84,p. 1782 - 1792
    Zh. Obshch. Khim.,2014,vol. 84,p. 1546 - 1556,11
[2]Chemistry of Heterocyclic Compounds,2014,vol. 50,p. 19 - 25
    Khim. Geterotsikl. Soedin.,2014,vol. 50,p. 24 - 31,7
[3]Chemistry of Heterocyclic Compounds,2019
    Khim. Geterotsikl. Soedin.,2019,vol. 556,p. 508 - 516,9
[4]Journal of Medicinal Chemistry,2006,vol. 49,p. 3857 - 3871

5
[ 27329-70-0 ]
[ 585-76-2 ]
[ 304884-54-6 ]

Yield	Reaction Conditions	Operation in experiment
96%	With C11H8Cl4N2O3Pd; potassium carbonate; In methanol; water; N,N-dimethyl-formamide; at 100℃; for 0.166667h;	General procedure: To a mixture of 1.20 mmol of arylboronic acid, 1.00 mmol of aryl(hetaryl) bromide, 3.2 mg (0.01 mmol) of Bu4NBr (for water insoluble aryl halides) and 0.35 g (2.5 mmol) K2CO3 in 5 mL of H2O (or in 5 mL of equal volumes of water and methanol) pre-heated to 80C was added 0.1 mL of a suspension of L1-4PdCl2 complexes (0.1 mol % Pd) in methanol-DMF mixture (0.01 M). The reaction mixture was stirred vigorously at the same temperature (Table 4) to complete conversion. The reaction progress was monitored by TLC (eluent hexane-Et2O, 3 : 1). In the case of activated aryl bromides the reaction was highly exothermic that should be considered at the synthesis scaling. If the reaction products were aryl(hetaryl)benzoic acids, to obtain ananalytically pure sample the reaction mixture was diluted with water, heated, and filtered from mino ramounts (~ 0.1 mol %) of palladium black. Then about 10-15 vol % of alcohol was added, the mixture wa sheated to ~50C and acidified carefully with 10% HCl to adjusting pH = 2-3. As a result, the formed precipitate was filtered off and dried to provide analytically pure samples without the use of chromatographic methods. In the case of water-insoluble biaryls (heterobiaryls), the reaction mixture was diluted with a saturated solution of NaCl, extracted with Et2O or EtOAc, the extract was dried with Na2SO4 and filtered through a bed of silica gel. The solvent was removed to give the target compound with a purity ? 99% .Analytically pure sample was obtained by recrystallization from the minimum amount of aqueous alcohol (about 10-20 vol % of 2), or by conversion of amines to hydrochlorides.
0.21 g	With 2-[5-(4-methylphenyl)isoxazol-3-yl]-5-(5-phenylisoxazol-3-yl)-1,3,4-oxadiazole·2PdCl2; potassium carbonate; In methanol; water; N,N-dimethyl-formamide; at 20℃; for 0.416667h;	General procedure: A 0.01 solution of L1-4·PdCl2 (0.2 mol % Pd) in DMF (0.1-0.2 ml)(or 0.8-4 mg of the respective Pd/Fe composite) was addedto a mixture of aryl(hetaryl)boronic acid (1.20 mmol), aryl-(hetaryl) bromide (1.00 mmol), Bu4NBr (3.2 mg, 0.01 mmol,used in the case of aryl halides that were insoluble in water),and K2CO3 (0.35 g, 2.5 mmol) in 2 (10 ml) (or in 10 mlof 1:1 methanol-water mixture). The reaction mixture wasvigorously stirred at the indicated temperature until fullconversion was obtained. The reaction progress wascontrolled by TLC method (eluent hexane-Et2O, 2:1). In thecase of activated aryl bromides, the reaction was veryexothermic, therefore it was important to use an effectivereflux condenser for larger scale syntheses. In the cases when the reaction products were aryl(hetaryl)benzoic acids, analytically pure samples were obtainedby diluting the reaction mixture with water, heating, filteringin order to remove an insignificant amount (~0.2 mol %) ofpalladium black and the homocoupling product, diluted with10-15% (v/v) of ethanol, heated to ~50C, and slowly,while stirring, acidified with 5% HCl to pH 2-3. Theprecipitate that formed after cooling was easily filtered, andpure compounds were isolated without a need forchromatographic separation. In the case when Pd/Fe wasused, the catalyst was separated after the completion of thereaction with the aid of an external magnet and the reactionmixture was used as described above. The recovered Pd/Fecatalyst could be used again after washing with water andacetone. In the case of biaryls (heterobiaryls) that wereinsoluble in water, the reaction mixture was diluted withsaturated NaCl solution, extracted with Et2O or EtOAc, theextract was dried over Na2SO4 and filtered through a thinsilica gel layer. The solvent was evaporated on a rotaryevaporator, and the residue, as a rule, had a purity of atleast 99%. Analytically pure samples were obtained by recrystallization of biaryls from a minimal amount ofaqueous alcohol (10-20% (v/v) 2) or by converting theamines to hydrochlorides. The residual palladium contentin the target products was in the range from 0.5 to 2.2 ppmaccording to the results of atomic absorption spectroscopy. 4'-Methoxybiphenyl-3-carboxylic acid (26). White crystalline powder, mp 203.4-204C (mp 202-203C16).1H NMR spectrum, delta, ppm (J, Hz): 3.83 (3H, s, CH3O);7.05 (2H, dd, J = 6.8, J = 2.1, H-3',5'), 7.56 (1H, t, J = 7.7, Ar), 7.66 (2H, dd, J = 6.8, J = 2.1, H-2',6'); 7.83-7.94(2H, m, Ar); 8.11 (1H, dd, J = 7.8, J = 2.0, H-4); 13.12(1H, br. s, COOH). 13C NMR spectrum, delta, ppm: 54.3(CH3O); 114.0; 127.2; 127.4; 127.6; 128.5; 130.6; 131.0;132.4; 141.0; 159.7; 168.5 (COOH). Found, %: C 73.61;H 5.37. C14H12O3. Calculated, %: C 73.67; H 5.30.

Reference： [1]Russian Journal of General Chemistry,2016,vol. 86,p. 68 - 81
Zh. Obshch. Khim.,2016,vol. 86,p. 75 - 88,14
[2]Journal of Medicinal Chemistry,2006,vol. 49,p. 3857 - 3871
[3]Chemistry of Heterocyclic Compounds,2017,vol. 53,p. 1340 - 1349
Khim. Geterotsikl. Soedin.,2017,vol. 53,p. 1340 - 1349,10

6
[ 27329-70-0 ]
[ 106291-80-9 ]
4-(5-formyl-furan-2-yl)-3-hydroxy-benzoic acid methyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 3857 - 3871

7
[ 27329-70-0 ]
[ 450-88-4 ]
5-(4-fluoro-2-methoxyphenyl)furan-2-carbaldehyde [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 3857 - 3871

8
[ 27329-70-0 ]
[ 121219-03-2 ]
5-(2-fluoro-4-hydroxy-phenyl)-furan-2-carbaldehyde [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 3857 - 3871

9
[ 27329-70-0 ]
[ 231278-20-9 ]
[ 231278-84-5 ]

Yield	Reaction Conditions	Operation in experiment
98.7%	With potassium carbonate;palladium diacetate; In tetrahydrofuran; ethanol; for 0.666667h;Reflux;Product distribution / selectivity;	Example 13: preparation of crystalline lapatinib aldehyde base[00098] To a 3L reactor lOOg of compound of formula C, 37.35g of 5-fo?nyl-2- furanboronic acid, 1.33g of palladium acetate, 54.66g of potassium carbonate, 750 ml of absolute ethanol and 750ml of THF were added. The suspension was stirred and heated to reflux (T(jacket) = 75C) for 40 minutes. The reaction mixture was cooled to room temperature (T(jacket) = 200C) and diluted with 750 ml of THF and 750 ml of absolute ethanol. The resulting mixture was stirred at 250C for an hour. Inorganic salts were filtered off in vacuum, washed with 100 ml of absolute ethanol, 100 ml of THF and discarded. The filtrate combined with washings was transferred into a 1OL reactor equipped with a mechanical stirrer and a dropping funnel. 3L of water was added dropwise into the solution of lapatinib-aldehyde base in EtOH/THF (1 :1) for an hour (T(jacket) = 200C). The resulting yellow suspension was stirred at RT (T(jacket) = 200C) for 1.5 hour. The yellow solid was filtered in vacuum and washed over the filter with 100 ml of cold absolute ethanol. It was allowed to dry in a vacuum oven at 400C for 16 hours, and additional 24 hours in vacuum oven at 600C to give 92.56g of final product (Yield - 98.7%; Purity - 99.12%)
97.7%	With palladium; triethylamine; In tetrahydrofuran; ethanol; at 65℃; for 7h;Inert atmosphere;	Under the protection of nitrogen, to the 3L joins the type three sequentially in the bottle (IV) compound (100g, 0.198mol), 5-carboxaldehyde furan -2 boric acid (55.4g, 0 . 396mol), triethylamine (60.1g, , 0 . 594mol), thf (1000 ml), ethanol (500 ml), N2deaerization after replacing three times, heating to 65 C, stirring dissolution cleaning. By adding palladium catalyst, temperature control reaction 7h rear, monitoring TLC (developing solvent DCM: MeOH=30:1) to (IV) compound the reaction is complete. The reaction solution is 40g diatomaceous earth filtration, filtrate to room temperature, to its dropping 1000 ml purified water, stirring the mixture at room temperature for 1h, filtering, 45 C drying to obtain pale brown solid, that is, the compound of formula (III) 91.6g, HPLC purity 96.7%, the yield is 97.7%.
96%	With triethylamine;palladium 10% on activated carbon; In methanol; 1,2-dimethoxyethane; at 45 - 50℃; for 15h;Inert atmosphere;	(iii) Preparation of 5-[4-[3-chloro-4-(3-fluorobenzyloxy)-aniIino]-6-quinazolinyl)- furan-2-carbaIdehyde (4)Into a two liter four-necked round bottomed flask, 1000 mL of 1,2-dimethoxyethane, 50.0 g of N-(3-chloro-4-(3-fluorobenzyloxy)phenyl)-6-iodo-quinazolinamine obtained from the previous step(ii), 5-formyl-2-furyl boronicacid (21.5 g), triethylamine (30.5 g), 10% Pd on carbon (wet) (2.5 g) suspended in 500 mL of methanol were charged under stirring. The mass was maintained at 45-50 C for about 15 hours under nitrogen atmosphere and the completion of the reaction was monitored by TLC. The catalyst was filtered and the filtrate was quenched into two liters of water and stirred well. The product was filtered and dried to get 45.0 g (96% of theory) of 5-[4-3-chloro-4-(3-fluorobenzyloxy)-anilino]-6-quinazolinyl)- fiuran.-2-carbaldehyde as a greenish yellow amorphous powder. Purity: 99.6% by HPLC Melting range: 224-228 C

96%	With triethylamine;palladium 10% on activated carbon; In methanol; 1,2-dimethoxyethane; at 45 - 50℃; for 15h;Inert atmosphere;	(iii) Preparation of 514-[3-chloro-4-(3-fluorobenzyloxy)-anilino]-6-quinazolinyl)-furan-2-carbaldehyde (4)Into a two liter four-necked round bottomed flask, 1000 mL of 1,2-dimethoxyethane, 50.0 g of N-(3-chloro-4-(3-fluorobenzyloxy)phenyl)-6-iodo-quinazolinamine obtained from the previous step (ii), 5-formyl-2-furyl boronicacid (21.5 g), triethylamine (30.5 g), 10% Pd on carbon (wet) (2.5 g) suspended in 500 mL of methanol were charged under stirring. The mass was maintained at 45-50 C. for about 15 hours under nitrogen atmosphere and the completion of the reaction was monitored by TLC. The catalyst was filtered and the filtrate was quenched into two liters of water and stirred well. The product was filtered and dried to get 45.0 g (96% of theory) of 5-[4-3-chloro-4-(3-fluorobenzyloxy)-anilino]-6-quinazolinyl)-furan.-2-carbaldehyde as a greenish yellow amorphous powder.Purity: 99.6% by HPLCMelting range: 224-228 C.
92%	With palladium on activated charcoal; triethylamine; In methanol; ethanol; at 60℃; for 3h;	In a 1 L reaction flask, 50 g (10 mmol) of compound II was added in sequence,Compound III 18g (13mmol), ethanol 600ml, triethylamine 50ml,100 ml of methanol and 1 g of palladium carbon, stirred uniformly, and heated to 60 C for 3 hours.After the reaction is completed, palladium carbon is recovered by filtration, the filtrate is desolvated, the desolvation is completed, and 500 ml of water is added.After stirring at room temperature for 1 hour, it was filtered to give 43.1 g of pale yellow solid, Compound IV.Yield 92%, HPLC purity 98.46%
91%	With palladium 10% on activated carbon; triethylamine; In methanol; 1,2-dimethoxyethane; at 50℃; for 14h;	Example 10 - Comparative example in accordance with EPI 7929025-(4-(3-Chloro-4-(3-fluorobenzyloxy)phenylamino)chinazolin-6-yl)furan-2-carbaldehyde (I)Triethylamine (0.2 ml) was added to a mixture of the boronic acid VI (104 mg, 0.74 mmol, 1.5 equiv.), III (250 mg, 0.49 mmol) and 10 % Pd/C (13 mg, 0.012 mmol, 2.5mol. %), DME (4 ml) and methanol (2 ml) and the resulting substance was stirred at the temperature of 50C for 14 hours. After working, 184 mg (78%) of a yellow powdery substance was obtained containing 91% of the title compound I and 8% of the unreacted input substance Ill according to H PLC.
83.4%	With palladium 10% on activated carbon; triethylamine; In methanol; 1,2-dimethoxyethane; at 50℃; for 0.5h;	General procedure: To a 100 mL round bottomed flask, residue C1-4 (0.60 mmol), <strong>[27329-70-0]5-formyl-2-furanboronic acid</strong> (0.90 mmol), Pb/C 10%, triethylamine (2.4 mmol), 1,2-dimethoxyethane (60 mL), methanol (30 mL) were added. The suspension was stirred and heated to 50 C for 0.5 h. The reaction mixture was filtered with diatomite and the filter cake was washed with THF (3 × 10 mL). The filtrate combined with washings was evaporated. The crude product was chromatographed by silica gel, eluted with EtOAc/CHCl3 (1:10) to afford compound D1-4 as orange solid (yield 57.2~83.4%). 4 1.2.1.1 4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(5-formylfuran-2-yl)quinazoline (D1) Yield 83.4%. 1H NMR (400 MHz, DMSO-d6) delta(ppm): 10.08 (s, 1H), 9.68 (s, 1H), 8.94 (d, J = 1.6 Hz, 1H), 8.60 (s, 1H), 8.33 - 8.25 (m, 1H), 8.00 (d, J = 2.6 Hz, 1H), 7.85 (d, J = 8.8 Hz, 1H), 7.73 (dd, J = 8.8, 3.1 Hz, 2H), 7.49 (td, J = 8.0, 6.0 Hz, 1H), 7.40 (d, J = 3.8 Hz, 1H), 7.34 (dd, J = 11.9, 5.1 Hz, 2H), 7.29 (d, J = 9.0 Hz, 1H), 7.23 - 7.16 (m, 1H), 5.27 (s, 2H) (Figure S7).
83.4%	With palladium 10% on activated carbon; In methanol; 1,2-dimethoxyethane; at 50℃; for 0.5h;	General procedure: As our previously described,3 to a 100 mL round bottomed flask, residue 13a-13c (0.60 mmol), <strong>[27329-70-0]5-formyl-2-furanboronic acid</strong> (0.90 mmol), Pb/C 10%, triethylamine (2.4 mmol), 1,2-dimethoxyethane (60 mL) and methanol (30 mL) were added. The suspension was stirred and heated to 50 for 0.5 h. The reaction mixture was filtered with diatomite and the filter cake was washed with THF (3 × 10 mL). The filtrate combined with washings was evaporated. The crude product was chromatographed by silica gel, eluted with EtOAc/CHCl3 (1:10) to afford compound 14a-14c as orange solid (yield 65.2% ~ 83.4%). 1.2.1.1 4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(5-formylfuran-2-yl)quinazoline (14a) Orange power, yield: 83.4%.
78%	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,2-dimethoxyethane; ethanol; water; at 60℃; for 3h;	Preparation analogous to Hosoya et al. (Danthrone Analogues Revisted: General Synthesis and Specific Functions Capable of Discriminating Two Rinds of Ca2+ Release from Sarcoplasmic Rerticulum of Mouse Skeletal Muscle. Bioorg. Med, Chem. 2003, 11, 663-673). A mixture of 16 (5.00 g; 9.88 mmol), the respective arylboronic acid (17a, 17b, 22b: Aldrich; 17c, 17d Alfa Aesar 22a Rare Chemicals ) (13.1 mmol), (PPh3)2PdCl2 (0.35 g; 0.5 mmol), DME (30 mL), ethanol (20 mL) and 2M aqueous Na2CO3 (30 mL) was heated at 60 GC for 3h. After being cooled to room temperature, the crude product precipitated as a yellow solid. It was removed by filtration, washed with water and dried in vacuum over night. Crystallisation from acetone afforded the title compound in sufficient purity for further synthesis. An analytical sample was obtained column chromatography (SiO2; CH2Cl2ZeUIyI acetate = 4:1).; 5-{4-[3-Chloro-4-(3-fluorobenzyloxy)phenylamiDo]-quinazolin-6-yl}furan-2- carbaldehyde (18a) <n="71"/>(Roschangar et al.; Use of lithium N,O~dimethylhydroxylamide as an efficient in situ protecting agent for aromatic aldehydes. Tertrahedron 2002, 55, 1657-1666): Yield (3.65 g, 78%). mp: 229.8-234.1 0C. 1H-NME. (DMSO-[D6]): delta (ppm) = 5.26 (s, 2H), 7.17 (dt, IH, J = 2.5 Hz, J = 8.5), 7.26-7.34 (m, 3H), 7.40 (d, IH, J - 3.6 Hz), 7,43-7.50 (m, IH), 7.68-7.74 (m, 2H), 7.84 (d, IH, J = 8.5 Hz), 7.98 (d, IH, J = 2.5 Hz), 8.28 (dd, IH, J = 1.1 Hz, J = 8.8 Hz), 8.58 (s, IH), 8.95 (d, IH, J = 0.8 Hz), 9.66 (s, IH), 10.10 (s, IH, exchangeable). + p ESI m/z (%): 476 [MH-H+J+' (37); 474 [M+HT (100); - p ESI m/z (%): 474 [M-H+]' (37), 472 [M-H+]" (100). IR (KBr): 3399, 1673 cm"1-
66.2%	With triethylamine;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In tetrahydrofuran; ethanol;Heating / reflux;	N-(3-Chloro-4-(3-fluorobenzyloxy)phenyl)-6-iodoquinazolin-4-amine (387 mg, 0.77 mmol) and 5-formylfuran-2-ylboronic acid (129 mg, 0.92 mmol) were added into the mixture of THF (10 rnL) , ethanol (5 mL) and Et3N (0.3 rnL) under N2 atmosphere. Then PdCl2(dppf) (26 mg, 0.03 mmol) was added into the mixture. The mixture was refluxed overnight. Then the solvent was removed in vacuo, the residue was chromatographed on silica gel with ethyl acetate to give product 1406- 174 (240 mg, 66.2%): LC-MS: 474 [M+l]+, 1H NMR (DMSO-J6): delta 5.20 (s, 2 H), 7.17 (m, IH), 7.29 (m, 3H), 7.41 (m, 2H), 7.74 (m, 2H), 7.86 (d, J= 9.0 Hz, 1 H), 7.97 (s,l H), 8.31 (d, J= 9.0 Hz, 1 H), 8.56 (s, 1 H), 8.96 (s, 1 H), 9.66 (s, 1 H), 10.11 (s, I H).
	With triethylamine;palladium on activated carbon; In methanol; 1,2-dimethoxyethane;	Example 1 Preparation of 5-(4-[3-chloro-4-(3-fluorobenzyloxy)-anilino]-6-quinazolinyl)-furan-2-carbaldehyde To a reaction vessel was added N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-iodo-4-quinazolinamine (100 mg; 0.198 mmol), 2-formylfuran-5-boronic acid (Frontier Scientific, 42 mg; 0.297 mmol), 10% palladium on activated carbon (5 mg; 0.05 wt), DME (2.0 mL), MeOH (1.0 mL) and triethylamine (83 muL). After heating at 50 C. for 14 h, a HPLC indicated 98.5% clean conversion. 1H NMR (d6-DMSO) delta: 11.44 (s, 1H), 9.38 (s, 2H), 9.11 (s, 1H), 8.90 (s, 1H), 8.39 (dd, 1H, J=8 and 4 Hz), 7.89 (d, 1H, J=12 Hz), 7.84 (d, 1H, J=4 Hz), 7.60 (dd, 1H, J=8 and 4 Hz), 7.47-7.42 (m, 2H), 7.44 (AA'BB', 2H, JAB=8 Hz), 7.35-7.25 (m, 3H), 7.24 (d, 1H, J=4 Hz), 7.16 (dt, 1H, J=8 and 4 Hz), 7.06 (AA'BB', 2H, JAB=8 Hz, 6.84 (d, 1H, J=4 Hz), 5.27 (s, 2H), 4.43 (s, 2H), 3.61-3.50 (m, 2H), 3.47-3.36 (m, 2H), 3.09 (s, 3H), 2.23 (s, 6H).
	With 1,2-dimethoxyethane; triethylamine;palladium 10% on activated carbon; In methanol;Inert atmosphere;	(iv) Preparation of 5-[4-[3-chloro-4-(3-fluorobenzyIoxy)-anilino]-6- quinazolinyl)- furan-2-carbaldehyde (4)Into a two liter four-necked round bottomed flask, 1000 mL of 1,2-dimethoxyethane, 50.0 g of N-(3-chloro-4-(3-fluorobenzyloxy)phenyl)-6-iodo-quinazolinamine obtained from the previous step(iii), 5-formyl-2-furyl boronicacid (21.5 g), triethylamine (30.5 g), 10% Pd on carbon (wet) (2.5 g) suspended in 500 mL of methanol were charged under stirring. The mass was maintained at 45-50 C for about 15 hours under nitrogen atmosphere and the completion of the reaction was monitored by TLC. The catalyst was filtered and the filtrate was quenched into two liters of water and stirred well. The product was filtered and dried to get 45.0 g (96% of theory) of 5-[4-3-chloro-4-(3-fluorobenzyloxy)-anilino]-6-quinazolinyl)-fiuran.-2- carbaldehyde as a greenish yellow amorphous powder.Purity: 99.6% by HPLC Melting range: 224-228 C
7 g	With palladium diacetate; potassium carbonate; In tetrahydrofuran; ethanol; for 1h;Inert atmosphere; Reflux;	A mixture of N-(3-chloro-4-(3-fluorobenzyloxy)phenyl)-6-iodoquinazolin-4-amine (10.2 g, 20 mmol), 5-formylfuran-2-ylboronic acid (3.8 g, 27 mmol), Pd(OAc)2 (0.4 g, 1.8 mmol) and K2CO3 (11.0 g, 80 mmol) in THF (100ml) and ethanol (100ml) was stirred and heated to reflux for 1 h in a nitrogen atmosphere. The reaction mixture was cooled to room temperature and diluted with THF (200 ml) and ethanol (200 ml). Solid was filtered off and washed with 100 ml of THF. The combined organic layers were concentrated, diluted with H2O (500 ml) and stirred for 1 h. The yellow solid was collected, washed with ethanol (100 ml) and dried in a vacuum oven for two days at room temperature to give intermediate C (7 g, purity 98%). To a solution of intermediate C (0.47 g, 1 mmol) and morpholine (0.14 ml, 1.6 mmol) in CH2Cl2 (100 ml) and methanol (30 ml) was added NaBH(OAc)3 (0.380 g, 1.80 mmol). After 25 h, the reaction was diluted with H2O (300 mL) and extracted with CH2Cl2 (3 x 250 ml). The organic layers were combined, dried (Na2SO4)and concentrated. Chromatography of the residue (in CH2Cl2/MeOH) gave the title compound as an orange solid (0.21 g, 39%).
	With N-ethyl-N,N-diisopropylamine;palladium 10% on activated carbon; In ethanol; at 70℃; for 3h;	A mixture of N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-iodo-4- quinazolinamine - compound D (1wt), boronic acid - compound E (0.37wt , 1.35equiv), and 10% palladium on charcoal (0.028wt,50% water wet) was slurried in IMS (15vol). The resultant suspension was stirred for 5 minutes, treated with di- isopropylethylamine (0.39vol, 1.15equiv) and then heated to ca 70C for ca 3 hours when the reaction was complete (determined by HPLC analysis). The mixture was diluted with tetrahydrofuran (THF, 15vol) and then hot-filtered to remove the catalyst. The vessel was rinsed with IMS (2vol). A solution of p-toluenesulfonic acid monohydrate (1.5wt, 4 equiv) in water (1.5vol) was added over 5-10 minutes to the filtered solution maintained at 65C. After crystallisation the suspension was stirred at 60-65C for 1 hour, cooled to ca 25C over 1 hour and stirred at this temperature for a further 2 hours. The solid was collected by filtration, washed with IMS (3vol) then dried in vacuo at ca 50C to give the compound F as a yellow-orange crystalline solid (isolated as the ethanol solvate containing approximately 5%w/w EtOH).
	With N-ethyl-N,N-diisopropylamine;palladium 10% on activated carbon; In ethanol; at 70℃; for 3h;	A mixture of N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-iodo-4- quinazolinamine - compound D (1wt), boronic acid - compound E (0.37wt , 1.35equiv), and 10% palladium on charcoal (0.028wt ,50% water wet) was slurried in IMS (15vol). The resultant suspension was stirred for 5 minutes, treated with di- isopropylethylamine (0.39vol, 1.15equiv) and then heated to ca 70C for ca 3 hours when the reaction was complete (determined by HPLC analysis). The mixture was diluted with tetrahydrofuran (THF, 15vol) and then hot-filtered to remove the catalyst. The vessel was rinsed with IMS (2vol).
	With N-ethyl-N,N-diisopropylamine;palladium 10% on activated carbon; In isopropyl methanesulfonate; water; at 70℃; for 3h;Product distribution / selectivity;	A mixture of N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-iodo-4- quinazolinamine (1wt), boronic acid (0.37wt , 1.35equiv), and 10% palladium on charcoal (0.028wt ,50% water wet) was slurried in IMS (15vol). The resultant suspension was stirred for 5 minutes, treated with di-isopropylethylamine (0.39vol, 1.15equiv) and then heated to ca 700C for ca 3 hours when the reaction was complete (determined by HPLC analysis). The mixture was diluted with tetrahydrofuran (THF, 15vol) and then filtered (hot - through GFA filter paper) to remove catalyst. The vessel was rinsed with IMS (2vol).A solution of p-toluenesulfonic acid monohydrate (1.54wt, 4.1equiv) in water (3vol) was added over 5-10 minutes to the filtered solution maintained at 65C. After crystallisation the suspension was stirred at 60-65C for 1 hour, cooled to ca 25C over 1 hour and stirred at this temperature for a further 2 hours. The solid was collected by filtration, washed with IMS (3vol) then dried in vacuo at ca 500C to give the tile compound as a yellow-orange crystalline solid.
		A mixture of lambda/-(3-chloro-4-[(3-fluorophenyl)methyl]oxy}phenyl)-6- iodo-4-quinazolinamine (1 wt), (5-formyl-2-furanyl)boronic acid (0.374 wt, 1.35eq) and 10% Palladium on charcoal (0.028 wt 50% water wet) is slurried in ethanol(industrial methylated spirits, 15 vols) to give a grey suspension. The resultant slurry is stirred for 5 minutes and then treated with lambda/,lambda/-di-isopropylethylamine (0.396 vols,1.15eq.). The reaction slurry is heated to 700C for typically 3 hours when the reaction is complete (by HPLC analysis). The mixture is a thick green slurry at this point which is treated with THF (15 vols) to dissolve the product that has precipitated, leaving only the Pd/C catalyst out of solution. The mixture is then filtered hot throughGFA filter to remove the catalyst. The vessel is rinsed with IMS (1vol) and the wash used to rinse catalyst bed. A solution of p-toluenesulfonic acid monohydrate (1.50wt, 4.0 eq.) in water (1.5 vols) is added to the filtered solution over 5 minutes at 65C.The reaction solution is cooled to 600C, with crystallization observed at 60-650C. <n="47"/>The resultant slurry is then stirred for at least 1 hour at 600C and then cooled to 20- 25C and then held at this temperature for a further 1 hour. The product is isolated by filtration and the cake washed with IMS (3vols). The product may be stored as a wet cake or dried.
		Stage 2: Preparation of 5-(4-[3-chloro-4-(3-fluorobenzyloxy)-anilino]-6- quinazolinyl)-furan-2-carbaldehyde 4-methylbenzenesulfonate A mixture of N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-iodo-4- quinazolinamine (1wt), boronic acid (0.37wt , 1.35equiv), and 10% palladium on charcoal (0.028wt,50% water wet) was slurried in IMS (15vol). The resultant suspension was stirred for 5 minutes, treated with di- isopropylethylamine (0.39vol, 1.15equiv) and then heated to ca 70C for ca 3 hours when the reaction was complete (determined by HPLC analysis). The mixture was diluted with tetrahydrofuran (THF, 15vol) and then filtered (hot - through GFA filter paper) to remove catalyst. The vessel was rinsed with IMS (2vol).

Reference： [1]Patent: WO2010/17387,2010,A2 .Location in patent: Page/Page column 24
[2]Patent: CN105503839,2016,A .Location in patent: Paragraph 0046; 0047
[3]Patent: WO2010/61400,2010,A1 .Location in patent: Page/Page column 15
[4]Patent: US2011/263852,2011,A1 .Location in patent: Page/Page column 12
[5]Patent: CN109503559,2019,A .Location in patent: Paragraph 0019
[6]Patent: WO2014/59956,2014,A1 .Location in patent: Page/Page column 11; 12
[7]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 1584 - 1587
[8]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 4309 - 4313
[9]Journal of Enzyme Inhibition and Medicinal Chemistry,2019,vol. 34,p. 1668 - 1677
[10]Patent: WO2009/63054,2009,A1 .Location in patent: Page/Page column 69-70
[11]Journal of Medicinal Chemistry,2010,vol. 53,p. 8546 - 8555
[12]ChemCatChem,2020,vol. 12,p. 2942 - 2946
[13]Patent: WO2008/33747,2008,A2 .Location in patent: Page/Page column 169-170
[14]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 4686 - 4691
[15]Patent: US2003/220354,2003,A1
[16]Patent: WO2011/39759,2011,A1 .Location in patent: Page/Page column 14
[17]European Journal of Medicinal Chemistry,2013,vol. 69,p. 833 - 841
[18]European Journal of Medicinal Chemistry,2014,vol. 87,p. 631 - 642
[19]Patent: WO2005/120512,2005,A2 .Location in patent: Page/Page column 24
[20]Patent: WO2005/120504,2005,A2 .Location in patent: Page/Page column 31
[21]Patent: WO2007/121279,2007,A2 .Location in patent: Page/Page column 41
[22]Patent: WO2007/121279,2007,A2 .Location in patent: Page/Page column 44-45
[23]Patent: WO2005/105094,2005,A2 .Location in patent: Page/Page column 45

10
[ 1448-87-9 ]
[ 27329-70-0 ]
[ 65237-59-4 ]

Reference： [1]Journal of the American Chemical Society,2007,vol. 129,p. 3358 - 3366

11
[ 220099-93-4 ]
[ 27329-70-0 ]
[ 957796-31-5 ]

Yield	Reaction Conditions	Operation in experiment
92%		To a solution of (2i?)-5'-bromo-3'H-spiro[4-azabicyclo[2.2.2]octane-2,2'-furo[2,3- &]pyridine] (6g, 20.3 mmol) in 400 mL of a DME:eta2O:EtOeta mixture (7:3:2) was added 5- formyl-2-furanboronic acid (5.67g, 40.5 mmol). The reaction mixture was purged with N2 <n="21"/>(directly into the solvent) and stirred for ten minutes until homogeneous. Solid Na2CO3 (8.6 g, 81.0 mmol) was added to the reaction mixture followed by Pd(PPh3)2Cl2 (711 mg, 1.0 mmol). The reaction mixture was again purged with N2 for 10 min, then heated at 65 0C for 6 h. The reaction mixture was stirred at rt overnight, then concentrated via rotary evaporator. The resulting residue was diluted with CHCl3 and filtered through diatomaceous earth. The CHCl3 filtrate was concentrated and the resulting residue was diluted with IN HCl and extracted with EtOAc (3 x 150 mL). The acidic aqueous layer was made basic with the addition of 2N aqueous NaOH (to pH~12) and the basic aqueous solution was extracted with CHCl3 (3x150 mL). The combined CHCl3 layer was washed with brine, dried (Na2SO4), filtered and concentrated to a solid (5.79 g, 92% yield). This material was used without further purification. 1H NMR (500 MHz, CDCl3) delta 1.46 - 1.53 (m, IH), 1.68 - 1.71 (m, 2H), 2.03 - 2.04 (m, IH), 2.22 - 2.26 (m, IH)5 2.78 - 2.94 (m, 3H), 2.97 (d, J= 14.7 Hz, IH), 3.00 - 3.04 (m, IH), 3.07 (d, J= 16.5 Hz, IH), 3.40 (d, J= U.I Hz, IH), 3.47 (d, J= 16.5 Hz, IH), 6.74 (d, J= 3.7 Hz, IH), 7.30 (d, J= 3.7 Hz, IH), 7.89 (s, IH), 8.48 (s, IH), 9.62 (s, IH) MS ES+, m/z = 311 (M+Hi).

Reference： [1]Patent: WO2007/133155,2007,A1 .Location in patent: Page/Page column 19-20

12
[ 1009303-44-9 ]
[ 27329-70-0 ]
C₂₂H₂₅N₅O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With potassium phosphate;bis(tri-t-butylphosphine)palladium(0); In 1,4-dioxane; at 170℃; for 0.75h;Microwave radiation;	The appropriate chloro-substrate (1 equiv) was dissolved in dioxane (0.16 M). 5-formyl-2- furylboronic acid (1.05 equiv), tripotassium phosphate (1.5 equiv) and bis(tri-t- butylphosphine)palladium (0.05 equiv) were added. The reaction vessel was sealed and exposed to microwave radiation (170 0C, medium absorption setting) for 45 minutes. Upon completion the reaction mixture was partitioned between water and CH2Cl2 and extracted with CH2Cl2. Combined organic phases were dried (MgSO4), filtered and concentrated in vacuo. The crude residue was purified by column chromatography on silica gel eluting with 40 to 100 % ethyl acetate in hexane to give the desired product.5 - [2,4-Bis-(3 -methyl-morpholin-4-yl)-pyrido [2,3 -d]pyrimidin-7-yl]-furan-2-carboxaldehyde: (100 % yield, 100 % purity) m/z (LC-MS, ESP): 424 [M+H]+ R/T = 2.75 min

Reference： [1]Patent: WO2008/23161,2008,A1 .Location in patent: Page/Page column 217-218

13
[ 13529-27-6 ]
[ 121-43-7 ]
[ 27329-70-0 ]

Reference： [1]Patent: WO2004/24738,2004,A1 .Location in patent: Page/Page column 13
[2]Organic and Biomolecular Chemistry,2003,vol. 1,p. 1447 - 1449

14
[ 5044-39-3 ]
[ 27329-70-0 ]
[ 1004111-79-8 ]

Reference： [1]Angewandte Chemie - International Edition,2007,vol. 46,p. 9215 - 9219

15
[ 918643-33-1 ]
[ 27329-70-0 ]
[ 1127329-37-6 ]

Yield	Reaction Conditions	Operation in experiment
84%	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,2-dimethoxyethane; ethanol; water; at 65℃; for 5h;	Example 36; N-(3-Fluoro-4-(2-(5-((2-methoxyethylamino)methyl)furan-2-yl)thieno[3,2-b]pyridin-7- yloxy)phenyl)-2-oxo-3 -phenylimidazolidine- 1 -carboxamide (110); Step 1. 5-(7-(2-Fluoro-4-nitrophenoxy)thieno[3,2-blpyridin-2-yl)furan-2-carbaldehyde (107); A stirred suspension of 7-(2-fluoro-4-nitrophenoxy)-2-iodothieno[3,2-b]pyridine (24) [US 2006/0287343 Al] (5.00 g, 12.01 mmol, scheme 4)], <strong>[27329-70-0]5-formyl-2-furanboronic acid</strong> (2.19g, 15.19 mmol), Pd(PPh3 )2C12 (422 mg, 0.6 mmol), Na2CO3 (8.53 g, 80.50 mmol) in a mixture of DME/ethano I/water (60 mL/40 mL/40 mL) was degassed with nitrogen for 15 min, and heated at 65C for five hours under nitrogen. The reaction mixture was allowed to cool to room temperature, and filtered. The cake was successively washed with water and AcOEt. The filtrate and washings were combined, extracted with AcOEt. The extract was successively washed with water, saturated solution of ammonium chloride, water and brine, and concentrated. The residue was combined with the cake, absorbed on silica gel and subjected to flash column chromatography on silica gel (eluents AcOEt/DCM: 10/90 to 20/90, then MeOH/DCM: 5/95) followed by trituration with AcOEt, to afford aldehyde 107 (3.886 g, 84% yield) as a pale clay solid. MS (m/z): 385.0 (M+H).

Reference： [1]Patent: WO2009/26717,2009,A1 .Location in patent: Page/Page column 102; 103

16
[ 630120-99-9 ]
[ 27329-70-0 ]
[ 1191923-28-0 ]

Yield	Reaction Conditions	Operation in experiment
46%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 94℃;Inert atmosphere;	Step 2:2-furaldehyde 4-boronic acid (10.2 g, 73 mmol), palladiumtetrakistriphenylphosphine (2.9 g, 2.4 mmol) and 5-benzyloxy-2-bromo- pyridine (6.4 g, 24 mmol) are diluted with an aqueous sodium carbonate solution (30 mL, 61 mmol), 1 ,2-dimethyoxethane (120 mL) and then degassed with argon over 5 minutes. The solution is heated to reflux (94 0C) overnight under argon. Upon cooling, the reaction mixture is diluted with ethyl acetate and water, and the aqueous phase is extracted with copious amounts of ethyl acetate. The combined organic extracts are washed with brine and concentrated in vacuo. The resulting residue is purified on silica with hexanes/ethyl acetate as the eluent to give an yellow solid, 3.1 g, 46%, LC/MS ESI m/z (M+H)+ = 280.4.

Reference： [1]Patent: WO2010/56585,2010,A2 .Location in patent: Page/Page column 72
[2]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 5321 - 5324

17
[ 25252-00-0 ]
[ 27329-70-0 ]
[ 1190223-45-0 ]

Reference： [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 7631 - 7639

18
[ 27329-70-0 ]
[ 56961-27-4 ]
[ 1190223-46-1 ]

Reference： [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 7631 - 7639
[2]Journal of Medicinal Chemistry,2011,vol. 54,p. 572 - 579

19
[ 27329-70-0 ]
[ 2476-35-9 ]
[ 1190223-44-9 ]

Reference： [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 7631 - 7639

20
[ 27329-70-0 ]
[ 3972-65-4 ]
[ 343604-13-7 ]

Yield	Reaction Conditions	Operation in experiment
72%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; ethanol; water; at 20 - 70℃; for 1.08333h;	To a round bottom flask containing 1-bromo-4-tert-butyl-benzene (1.5 g, 7.04 mmol) and 5-formyl-2-furan-boronic acid (1.47 g, 10.56 mmol) in dimethoxyethane (80 mL) and ethanol (20 mL) was added an aqueous solution of sodium carbonate (2.24 g, 21.12 mmol) m water (30 mL). The reaction mixture was stirred at room temperature for 5 minutes, followed by the addition of tetrakis(triphenylphosphine)palladium (404 mg, 0.35 mmol). The reaction mixture was heated at 70 C. for 1 h. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (500 mL) and water (50 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (2×150 mL). The combined organic extracts were washed with brine, dried (sodium sulfate) and concentrated under vacuum. The crude product was purified by silica gel chromatography eluting with 20% ethyl acetate in hexanes to afford 5-(4-tert-butyl-phenyl)-furan-2-carbaldehyde (1.16 g, 72%) as a dark brown solid. 1H NMR (400 MHz, CDCl3): delta 1.35 (9H, s), 6.80 (1H, d, J=3.6 Hz), 7.31 (1H, d, J=3.6 Hz), 7.44-7.7.48 (2H, m), 7.74-7.77 (2H, m), 9.64 (1H, s); APCI-MS: 228.34.

Reference： [1]Patent: US2010/210577,2010,A1 .Location in patent: Page/Page column 22; 29
[2]Organic and Biomolecular Chemistry,2012,vol. 10,p. 7402 - 7417

21
[ 27329-70-0 ]
[ 25109-28-8 ]
[ 1001010-46-3 ]

Yield	Reaction Conditions	Operation in experiment
53%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; ethanol; water; at 20 - 70℃; for 1.08333h;	To a round bottom flask containing <strong>[25109-28-8]1-bromo-4-cyclohexyl-benzene</strong> (1.5 g, 6.27 mmol) and 5-formyl-2-furan-boronic acid (1.32 g, 9.41 mmol) in dimethoxyethane (80 mL) and ethanol (20 mL) was added an aqueous solution of sodium carbonate (1:99 g, 18.81 mmol) in water (30 mL) The reaction mixture was stirred at room temperature for 5 minutes, followed by the addition of tetrakis(triphenylphosphine)palladium (358 mg, 0.31 mmol). The reaction mixture was heated at 70 C. for 1 h. The reaction mixture was then cooled to room temperature and diluted with ethyl acetate (500 mL) and water (50 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (2×150 mL). The combined organic extracts were washed with brine, dried (sodium sulfate) and concentrated under vacuum. The crude product was purified by silica gel chromatography, eluting with 15% ethyl acetate in hexanes to afford 5-(4-cyclohexyl-phenyl)-furan-2-carbaldehyde (850 mg, 53%) as a solid. 1H NMR (400 MHz, CDCl3): delta 1.28-1.46 (5H, m), 1.75-1.87 (5H, m), 2.53-2.54 (1H, m), 6.79 (1H, d, J=3.6 Hz), 7.26-7.32 (3H, m), 7.73-7.76 (2H, m), 9.63 (1H, s).

Reference： [1]Patent: US2010/210577,2010,A1 .Location in patent: Page/Page column 23

22
[ 27329-70-0 ]
[ 2051-99-2 ]
[ 1001010-49-6 ]

Yield	Reaction Conditions	Operation in experiment
31%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; ethanol; water; at 20 - 60℃;Inert atmosphere;	A mixture of <strong>[2051-99-2]1-bromo-4-isobutylbenzene</strong> (1.500 g, 7.04 mmol), 5-formyl-2-furanoboronic acid (1.477, 10.56 mmol) and sodium carbonate (3.134 g, 29.57 mmol) in a mixture of 1,2-dimethoxyethane (75 mL), ethanol (30 mL) and water (15 mL) was vigorously stirred and the reaction flask was purged with nitrogen. Tetrakis(triphenylphosphine)palladium(0) (0.404 g, 0.35 mmol) was added and the reaction mixture was heated at 60 C. for 3 h. The mixture was allowed to cool to room temperature and was left aside for 4 days. The reaction mixture was diluted with ether (200 mL) and washed successively with water (2×100 mL) and brine. The organic layer was separated, dried over sodium sulfate and concentrated. The residue was chromatographed on flash Silica, eluted with 5 to 10% ethyl acetate in hexanes to afford 5-(4-isobutyl-phenyl)-furan-2-carbaldehyde (490 mg, 31%). 1H NMR (400 MHz, CDCl3): 0.92 (6H, d, J=6.4 Hz), 1.90 (1H, m), 2.51 (2H, d, J=7.2 Hz), 6.80 (1H, d, J=3.6 Hz), 7.20 (2H, m), 7.31 (1H, dd, J=3.6, 1.2 Hz), 7.74 (2H, m), 9.63 (1H, s). ESI-MS: 227.1.

Reference： [1]Patent: US2010/210577,2010,A1 .Location in patent: Page/Page column 24

23
[ 30483-75-1 ]
[ 27329-70-0 ]
[ 1001010-56-5 ]

Yield	Reaction Conditions	Operation in experiment
60%	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,2-dimethoxyethane; ethanol; water; at 80℃; for 18.1667h;Inert atmosphere;	The reaction flask was flushed with nitrogen and charged with 4-(4-bromo-phenyl)-morpholine (2.134 g, 8.81 mmol), 5-formyl-furan-2-boronic acid (1.832 g, 13.10 mmol) and sodium carbonate (3.016 g, 28.46 mmol). A mixture of 1,2-dimethoxyethane (35 mL), ethanol (10 mL) and water (13 mL) was added and the reaction mixture was stirred for 10 min under a nitrogen atmosphere. Dichlorobis(triphenylphosphine) palladium(II) (0.205 g, 0.29 mmol) was added and the mixture was stirred and heated at 80 C. for 18 h. The mixture was cooled to room temperature and partitioned between ether (250 mL) and water (100 mL). The organic layer was separated, dried over sodium sulfate and concentrated under reduced pressure. The residue was chromatographed on flash Silica (100 mL, 20% ethyl acetate in hexanes) to afford 5-(4-morpholin-4-yl-phenyl)-furan-2-carbaldehyde (1.36 g, 60%). 1H NMR (400 MHz, CDCl3): delta 3.26 (2H, dd, J=5.2, 3.6 Hz), 3.87 (2H, dd, J=5.2, 3.6 Hz), 6.69 (1H, d, J=4.0 Hz), 6.93 (2H, m), 7.26 (1H, s), 7.30 (1H, d, J=4.0), 7.74 (2H, m), 9.58 (1H, s). ESI-MS: 258.0.

Reference： [1]Patent: US2010/210577,2010,A1 .Location in patent: Page/Page column 31

24
[ 27329-70-0 ]
[ 214958-32-4 ]
[ 1167626-70-1 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; water; at 20 - 90℃; for 21h;Inert atmosphere;	Intermediate 11: 6-[5-(Hydroxymethyl)furan-2-yl]imidazo[1,2-alpha]pyridine-2-carboxylic acid 11.1: Ethyl 6-(5-formylfuran-2-yl)imidazo[1,2-alpha]pyridine-2-carboxylate 2 g of ethyl 6-iodoimidazo[1,2-alpha]pyridine-2-carboxylate, 1.42 g of 5-formylfuran-2-boronic acid and 231 mg of [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium are degassed under vacuum and then suspended, under argon, in a degassed mixture of 30 ml of dioxane and 9.4 ml of a 2N aqueous sodium carbonate solution. The reaction mixture is heated at 90 C. for 5 hours, then stirred at 20 C. for 16 hours and concentrated to dryness. The residue is chromatographed on silica, elution being carried out with a mixture of ethyl acetate and hexane (90/10), with ethyl acetate and then with a mixture (99/1) of ethyl acetate and methanol. The fractions comprising the expected product are combined and concentrated to dryness under reduced pressure to give 884 mg of ethyl 6-(5-formylfuran-2-yl)imidazo[1,2-alpha]pyridine-2-carboxylate.1H NMR spectrum (d6-DMSO, delta in ppm): 9.64 (s, 1H), 9.20 (s, 1H), 8.66 (s, 1H), 7.86-7.74 (m, 2H), 7.72 (d, J=3.8, 1H), 7.37 (d, J=3.8, 1H), 4.33 (q, J=7.0, 2H), 1.33 (t, J=7.1, 3H).Mass spectrum (APCI): m/z=285 [M+H]+.
	With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; water; at 20 - 90℃; for 21h;Inert atmosphere;	20.1: Ethyl 6-(5-formylfuran-2-yl)imidazo[1,2-a]pyridine-2-carboxylate 2 g of <strong>[214958-32-4]ethyl 6-iodoimidazo[1,2-a]pyridine-2-carboxylate</strong>, 1.42 g of 5-formylfuran-2-boronic acid and 231 mg of [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium are degassed under vacuum and then suspended, under argon, in a degassed mixture of 30 mL of dioxane and 9.4 mL of aqueous 2N sodium carbonate solution. The reaction mixture is heated for 5 hours at 90 C., and then stirred for 16 hours at 20 C. and concentrated to dryness. The residue is chromatographed on silica, eluding with a mixture of ethyl acetate and hexane (90/10), with ethyl acetate and then with a mixture (99/1) of ethyl acetate and methanol. The fractions containing the expected product are combined and concentrated to dryness under reduced pressure to give 884 mg of ethyl 6-(5-formylfuran-2-yl)imidazo[1,2-a]pyridine-2-carboxylate. 1H NMR spectrum (DMSO-d6, delta in ppm): 9.64 (s, 1H), 9.20 (s, 1H), 8.66 (s, 1H), 7.86-7.74 (m, 2H), 7.72 (d, J=3.8, 1H), 7.37 (d, J=3.8, 1H), 4.33 (q, J=7.0, 2H), 1.33 (t, J=7.1, 3H). Mass spectrum (APCI): m/z=285 [M+H]+.
	With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; water; at 20 - 90℃; for 21h;Inert atmosphere;	2 g of <strong>[214958-32-4]ethyl 6-iodoimidazo[1,2-a]pyridine-2-carboxylate</strong>, 1.42 g of 5-formylfuran-2-boronic acid and 231 mg of [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium are degassed under vacuum and then suspended, under argon, in a degassed mixture of 30 mL of dioxane and 9.4 mL of aqueous 2N sodium carbonate solution. The reaction mixture is heated for 5 hours at 90 C., then stirred for 16 hours at 20 C. and concentrated to dryness. The residue is chromatographed on silica, eluding with a mixture of ethyl acetate and hexane (90/10), with ethyl acetate and then with a mixture (99/1) of ethyl acetate and methanol. The fractions containing the expected product are combined and concentrated to dryness under reduced pressure to give 884 mg of ethyl 6-(5-formylfuran-2-yl)imidazo[1,2-a]pyridine-2-carboxylate. 1H NMR spectrum (DMSO-d6, delta in ppm): 9.64 (s, 1H), 9.20 (s, 1H), 8.66 (s, 1H), 7.86-7.74 (m, 2H), 7.72 (d, J=3.8, 1H), 7.37 (d, J=3.8, 1H), 4.33 (q, J=7.0, 2H), 1.33 (t, J=7.1, 3H). Mass spectrum (APCI): m/z=285 [M+H]+.

Reference： [1]Patent: US2010/317656,2010,A1 .Location in patent: Page/Page column 11
[2]Patent: US2010/317675,2010,A1 .Location in patent: Page/Page column 19
[3]Patent: US2010/317686,2010,A1 .Location in patent: Page/Page column 12

25
[ 27329-70-0 ]
[ 3883-95-2 ]
[ 1175710-41-4 ]