[ CAS No. 330794-35-9 ] {[proInfo.proName]}

Name: 330794-35-9|tert-Butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzylcarbamate|95%
Brand: Ambeed
SKU: A114471
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2D 3D

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Quality Control of [ 330794-35-9 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 330794-35-9 ]

Product Details of [ 330794-35-9 ]

CAS No. :	330794-35-9	MDL No. :	MFCD06409942
Formula :	C₁₈H₂₈BNO₄	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	CUDCEJRRWNIPDL-UHFFFAOYSA-N
M.W :	333.23	Pubchem ID :	3415442
Synonyms :

Calculated chemistry of [ 330794-35-9 ]

Physicochemical Properties

Num. heavy atoms :	24
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.61
Num. rotatable bonds :	6
Num. H-bond acceptors :	4.0
Num. H-bond donors :	1.0
Molar Refractivity :	96.43
TPSA :	56.79 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 :	Yes
Log Kp (skin permeation) :	-5.91 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	3.41
Log Po/w (WLOGP) :	2.86
Log Po/w (MLOGP) :	1.83
Log Po/w (SILICOS-IT) :	2.24
Consensus Log Po/w :	2.07

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.84
Solubility :	0.0478 mg/ml ; 0.000143 mol/l
Class :	Soluble
Log S (Ali) :	-4.28
Solubility :	0.0174 mg/ml ; 0.0000522 mol/l
Class :	Moderately soluble
Log S (SILICOS-IT) :	-5.32
Solubility :	0.00158 mg/ml ; 0.00000474 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	0.0
Synthetic accessibility :	3.22

Safety of [ 330794-35-9 ]

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 [ 330794-35-9 ]

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

Upstream synthesis route of [ 330794-35-9 ]
Downstream synthetic route of [ 330794-35-9 ]

[ 330794-35-9 ] Synthesis Path-Upstream 1~5

1
[ 68819-84-1 ]
[ 73183-34-3 ]
[ 330794-35-9 ]

Yield	Reaction Conditions	Operation in experiment
97%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate In dimethyl sulfoxide at 85℃; for 12 h;	A solution of 4-bromobenzylamine (40.0g, 217.0 mmol) in THF (150 mL) was treated with di-tert-butyl dicarbonate (46.0g, 217 mmol) and stirred at rt for 1 h. The reaction mixture was concentrated in vacuo to afford a solid which was purified bychromatography (80:20 Hexanes: EtOAc) afforded the Boc protected amine (63.0 g, 95percent) as a white solid. A solution of the aryl bromide (30.0g, 98.0 mmol) in DMSO (100 mL) was treated with bis(pinacolato)diboron (30.0g, 118 mmol), KOAc (30.0g, 306 mmol), and PdCl₂(dppf) (0.2 mmol) and warmed to 85 °C for 12 h. The reaction mixture was diluted with EtOAc (250 mL) and washed with water (2 x 150 mL) and brine (100 mL). The organic layer was dried (Na₂SO₄) and concentrated in vacuo to afford a solid which was purification by chromatography (80:20 hexanes: EtOAc) afforded the desired cmpd (31.0 g, yield 97percent) as a white solid. ESI-MS (M+H)⁺: 334.

Reference： [1] Patent: WO2015/89327, 2015, A1, . Location in patent: Paragraph 0336
[2] Chemical Communications, 2013, vol. 49, # 30, p. 3110 - 3112
[3] Angewandte Chemie - International Edition, 2013, vol. 52, # 33, p. 8666 - 8670[4] Angew. Chem., 2013, vol. 125, # 33, p. 8828 - 8832,5
[5] Patent: US2007/179115, 2007, A1, . Location in patent: Page/Page column 19

2
[ 24424-99-5 ]
[ 138500-88-6 ]
[ 330794-35-9 ]

Yield	Reaction Conditions	Operation in experiment
99%	With triethylamine In dichloromethane at 20℃; for 2 h;	To a solution of 4-aminomethylphenylboronic acid, pinacol ester (CAS 138500-88-6) (1.2 g, 5.14 mmol) and Et₃N (1.42 ml, 10.28 mmol) in DCM (50 ml) stirred at room temperature, di-tert-butyldicarbonate (1.68 g, 7.72 mmol) was added. The mixture was stirred at room temperature for 2 hours. The solvent was evaporated in vacuum to yield 15 a residue which was treated with diethylether to yield intermediate compound 39 (1.7 g) as a solid, 99 percent) used in the next reaction step without further purification.

Reference： [1] Patent: WO2007/104783, 2007, A2, . Location in patent: Page/Page column 53
[2] Inorganic Chemistry, 2014, vol. 53, # 3, p. 1257 - 1259

3
[ 861359-74-2 ]
[ 24424-99-5 ]
[ 26177-44-6 ]
[ 73183-34-3 ]
[ 330794-35-9 ]

Yield	Reaction Conditions	Operation in experiment
78%	With potassium acetate In tetrahydrofuran; n-heptane; dichloromethane; ethyl acetate; N,N-dimethyl-formamide	b Tert-butyl N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl]carbamate A mixture of 4-bromobenzylamine hydrochloride (10.0 g, 45.0 mmol), di-tert-butyl dicarbonate (11.8 g, 54.0 mmol) and diisopropylethyl amine (8.7 g, 68 mmol) in tetrahydrofuran (100 mL) was heated at reflux for 1 hour. The mixture was cooled and the solvent evaporated under reduced pressure. The material was dissolved in dichloromethane (200 mL) and then washed with water, dried over magnesium sulfate, filtered and the filtrate concentrated under reduced pressure to provide an oil (14.0 g). The oil was dissolved in N,N-dimethylformamide (250 mL) then treated with diboron pinacol ester (11.4 g, 45 mmol), potassium acetate (13.2 g, 135 mmol) and [1.1'-bis(diphenylphosphino)ferrocene]dichloropalladium (II) complex with dichloromethane (1:1) (1.1 g, 1.35 mmol). The mixture was heated at 85° C. for 18 hours then cooled and the solvent removed under reduced pressure. The residue was stirred with dichloromethane (250 mL) then filtered through a pad of celite. The filtrate was concentrated under reduced pressure and the residue purified by flash chromatography on silica gel using heptane/ethyl acetate (8:2) as an eluent to provide tert-butyl N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl]carbamate (11.8 g, 78percent):: ¹H NMR (DMSO-d₆, 400 MHz) δ7.63 (d, 2H), 7.40 (t, 1H), 7.23 (d, 2H), 4.14 (d, 2H), 1.39 (s, 9H), 1.28 (s, 12H); RP-HPLC (Hypersil HS C18, 5 μm, 100 A, 250*4.6 mm; 25percent-100percent acetonitrile over 10 min, 1 mL/min) t_r 12.65 min.

Reference： [1] Patent: US2003/153752, 2003, A1,

4
[ 3959-07-7 ]
[ 330794-35-9 ]

Reference： [1] Angewandte Chemie - International Edition, 2013, vol. 52, # 33, p. 8666 - 8670[2] Angew. Chem., 2013, vol. 125, # 33, p. 8828 - 8832,5
[3] Patent: WO2015/89327, 2015, A1,

5
[ 24424-99-5 ]
[ 330794-35-9 ]

Reference： [1] Angewandte Chemie - International Edition, 2013, vol. 52, # 33, p. 8666 - 8670[2] Angew. Chem., 2013, vol. 125, # 33, p. 8828 - 8832,5
[3] Patent: WO2015/89327, 2015, A1,

[ 330794-35-9 ] Synthesis Path-Downstream 1~69

1
[ 24424-99-5 ]
[ 138500-88-6 ]
[ 330794-35-9 ]

Yield	Reaction Conditions	Operation in experiment
99%	With triethylamine; In dichloromethane; at 20℃; for 2h;	To a solution of 4-aminomethylphenylboronic acid, pinacol ester (CAS 138500-88-6) (1.2 g, 5.14 mmol) and Et3N (1.42 ml, 10.28 mmol) in DCM (50 ml) stirred at room temperature, di-tert-butyldicarbonate (1.68 g, 7.72 mmol) was added. The mixture was stirred at room temperature for 2 hours. The solvent was evaporated in vacuum to yield 15 a residue which was treated with diethylether to yield intermediate compound 39 (1.7 g) as a solid, 99 %) used in the next reaction step without further purification.

Reference： [1]Patent: WO2007/104783,2007,A2 .Location in patent: Page/Page column 53
[2]Inorganic Chemistry,2014,vol. 53,p. 1257 - 1259

2
[ 330794-35-9 ]
[ 950201-37-3 ]
[ 950201-66-8 ]

Yield	Reaction Conditions	Operation in experiment
77%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 150℃; for 0.166667h;Microwave irradiation;	To a solution of intermediate compound 39 (1.7 g, 5.14 mmol) in 1,4-dioxane (3 ml) and a saturated solution OfNaCO3 (3 ml) was added intermediate compound 3 (1.15 g, 4.28 mmol). The resulting solution was degassed using a stream of nitrogen and to this was added Pd(PPh3)4 (485.0 mg, 0.42 mmol). The reaction was then microwaved into a sealed tube at 150 0C for 10 min. The resulting reaction mixture was then filtered through a pad of celite and the filtrate concentrated in vacuo. The crude reaction mixture was then purified by flash chromatography (SiO2, DCM / MeOH(NH3) 9:1) to yield intermediate compound 40 (1.3 g, 77 %).

Reference： [1]Patent: WO2007/104783,2007,A2 .Location in patent: Page/Page column 53-54

3
[ 861359-74-2 ]
[ 24424-99-5 ]
[ 26177-44-6 ]
[ 73183-34-3 ]
[ 330794-35-9 ]

Yield	Reaction Conditions	Operation in experiment
78%	With potassium acetate; In tetrahydrofuran; n-heptane; dichloromethane; ethyl acetate; N,N-dimethyl-formamide;	b Tert-butyl N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl]carbamate A mixture of 4-bromobenzylamine hydrochloride (10.0 g, 45.0 mmol), di-tert-butyl dicarbonate (11.8 g, 54.0 mmol) and diisopropylethyl amine (8.7 g, 68 mmol) in tetrahydrofuran (100 mL) was heated at reflux for 1 hour. The mixture was cooled and the solvent evaporated under reduced pressure. The material was dissolved in dichloromethane (200 mL) and then washed with water, dried over magnesium sulfate, filtered and the filtrate concentrated under reduced pressure to provide an oil (14.0 g). The oil was dissolved in N,N-dimethylformamide (250 mL) then treated with diboron pinacol ester (11.4 g, 45 mmol), potassium acetate (13.2 g, 135 mmol) and [1.1'-bis(diphenylphosphino)ferrocene]dichloropalladium (II) complex with dichloromethane (1:1) (1.1 g, 1.35 mmol). The mixture was heated at 85 C. for 18 hours then cooled and the solvent removed under reduced pressure. The residue was stirred with dichloromethane (250 mL) then filtered through a pad of celite. The filtrate was concentrated under reduced pressure and the residue purified by flash chromatography on silica gel using heptane/ethyl acetate (8:2) as an eluent to provide tert-butyl N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl]carbamate (11.8 g, 78%):: 1H NMR (DMSO-d6, 400 MHz) delta7.63 (d, 2H), 7.40 (t, 1H), 7.23 (d, 2H), 4.14 (d, 2H), 1.39 (s, 9H), 1.28 (s, 12H); RP-HPLC (Hypersil HS C18, 5 mum, 100 A, 250*4.6 mm; 25%-100% acetonitrile over 10 min, 1 mL/min) tr 12.65 min.

Reference： [1]Patent: US2003/153752,2003,A1

4
[ 68819-84-1 ]
[ 73183-34-3 ]
[ 330794-35-9 ]

Yield	Reaction Conditions	Operation in experiment
97%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In dimethyl sulfoxide; at 85℃; for 12h;	A solution of 4-bromobenzylamine (40.0g, 217.0 mmol) in THF (150 mL) was treated with di-tert-butyl dicarbonate (46.0g, 217 mmol) and stirred at rt for 1 h. The reaction mixture was concentrated in vacuo to afford a solid which was purified bychromatography (80:20 Hexanes: EtOAc) afforded the Boc protected amine (63.0 g, 95%) as a white solid. A solution of the aryl bromide (30.0g, 98.0 mmol) in DMSO (100 mL) was treated with bis(pinacolato)diboron (30.0g, 118 mmol), KOAc (30.0g, 306 mmol), and PdCl2(dppf) (0.2 mmol) and warmed to 85 C for 12 h. The reaction mixture was diluted with EtOAc (250 mL) and washed with water (2 x 150 mL) and brine (100 mL). The organic layer was dried (Na2SO4) and concentrated in vacuo to afford a solid which was purification by chromatography (80:20 hexanes: EtOAc) afforded the desired cmpd (31.0 g, yield 97%) as a white solid. ESI-MS (M+H)+: 334.
85%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 100℃; for 12h;Inert atmosphere;	Under the protection of argon, compound (e) (600 mg, was added in sequence to a 50 mL two-necked bottle.2.0mmol)),Anhydrous potassium acetate (KOAc (588 mg, 6 mmol)),Diquinone borate (607 mg, 2.4 mmol) and PdCl 2 (dppf) (44 mg, 0.06 mmol), then add anhydrous dioxane 20 mL,The mixture was reacted at 100 C for 12 hours.After the reaction was completed, it was cooled to room temperature. Filtered with suction and the filtrate was extracted with ethyl acetate.Wash with water, wash with saturated NaCl, and combine the organic phases.Dry with anhydrous sodium sulfate. The solvent was removed under reduced pressure and separated by column chromatography.Petroleum ether (PE) / ethyl acetate (EA) = (20:1)A white solid (566 mg, 85%) was obtained.
	With potassium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In dimethyl sulfoxide; at 80℃; for 0.5h;	To a mixture of <strong>[68819-84-1]tert-butyl N-(4-bromobenzyl)carbamate</strong> (0.500 g), bis(pinacolato)diboron (0.488 g), potassium acetate (0.514 g) and dimethylsulfoxide (10.5 mL) was added [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium (II) complex with dichloromethane (0.043 g), and the resulting mixture was stirred at 80 C. for 30 minutes. The reaction mixture was cooled to room temperature and then partitioned between ethyl acetate (40 mL) and water (15 mL). The organic layer was washed with water/brine (1/1, 10 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: hexane/ethyl acetate=4/1) to give the title compound (0.579 g).

Reference： [1]Patent: WO2015/89327,2015,A1 .Location in patent: Paragraph 0336
[2]Patent: CN108794490,2018,A .Location in patent: Paragraph 0059; 0060; 0061
[3]Chemical Communications,2013,vol. 49,p. 3110 - 3112
[4]Angewandte Chemie - International Edition,2013,vol. 52,p. 8666 - 8670
Angew. Chem.,2013,vol. 125,p. 8828 - 8832,5
[5]Patent: US2007/179115,2007,A1 .Location in patent: Page/Page column 19

5
[ 330794-35-9 ]
[ 157245-77-7 ]
[ 880156-89-8 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 80℃; for 11h;	To a mixture of 1-bromo-3-pentyloxybenzene (0.365 g), tert-bytyl N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl) benzyl]carbamate (0.575 g), sodium carbonate (0.318 g), water (1.3 mL) and N,N-dimethylformamide (6.5 mL) was added tetrakis (triphenylphosphine) palladium(0) (0.087 g), and the resulting mixture was stirred at 80 C. for 11 hours. The reaction mixture was cooled to room temperature and then partitioned between ethylacetate (35 mL) and water (10 mL). The organic layer was washed successively with water/brine (2/1,15 mL) and brine (15 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on aminopropylated silica gel (eluent: hexane/ethyl acetate=6/1) to give the title compound (0.437 g)

Reference： [1]Patent: US2007/179115,2007,A1 .Location in patent: Page/Page column 19

6
[ 330794-35-9 ]
[ 1313441-12-1 ]
[ 1313441-59-6 ]

Yield	Reaction Conditions	Operation in experiment
72%	With sodium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; water; at 80℃;	In a 15 mL reaction tube was added 6-bromo-1-methyl-7-phenyl-1 H-pyrido[2,3- b][1 ,4]oxazin-2(3H)-one (40 mg, 0.125 mmol) and tert-butyl 4-(4,4,5,5-tetramethyl-1 ,3,2- dioxaborolan-2-yl)benzylcarbamate (50 mg, 0.150 mmol) in 1 ,4-dioxane (2 ml), followed by a solution of sodium carbonate (40 mg, 0.3 mmol) in water (0.5 ml) to give a white suspension. This was degassed by bubbling nitrogen for 10 minutes, followed by the addition of [1 ,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(ll) dichloromethane adduct (9 mg, 0.013 mmol). The reaction mixture was heated to 80C overnight. The reaction mixture was allowed to cool to room temperature, diluted with brine (4 ml) and extracted into ethyl acetate (3 x 4 ml). The combined organic phases were dried over Na2S04, filtered and concentrated to dryness under reduced pressure. The residue was purified by Biotage chromatography (cyclohexane:ethyl acetate, gradient elution from 90:10 to 20:80) to give the desired product as a white solid (40 mg, 72% yield). 1H-NMR (500 MHz, CDCI3) delta 7.27-7.32 (5H, m), 7.25 (1 H, s), 7.16-7.20 (2H, m), 7.10 (2H, d), 4.89 (2H, s), 4.81 (1H, br s), 4.26 (2H, br s), 3.39 (3H, s), 1.23 (9H, br s). LCMS (Method D): RT = 1.40 min, M+hT = 446.20.

Reference： [1]Patent: WO2011/77098,2011,A1 .Location in patent: Page/Page column 183

7
[ 330794-35-9 ]
[ 1313441-12-1 ]
[ 1313439-63-2 ]

Reference： [1]Patent: WO2011/77098,2011,A1

8
[ 330794-35-9 ]
[ 1313441-33-6 ]
[ 1313441-64-3 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; water; at 80℃; for 20h;	In a reaction tube was added 6-bromo-7-phenyl-1 H-pyrido[2,3-b][1 ,4]oxazin-2(3H)-one (0.19g, 0.623 mmol) and tert-butyl 4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2- yl)benzylcarbamate (0.25 g, 0.750 mmol) in 1 ,4-Dioxane (10 ml), followed by a solution of sodium carbonate (0.198 g, 1.868 mmol) in water (2.5ml) to give a suspension. This was degassed followed by the addition of PdCI2(dppf)-CH2CI2 adduct (0.051 g, 0.062 mmol). The resulting mixture was heated at 80 C for 20h.The reaction mixture was cooled down to room temperature and diluted with saturated sodium bicarbonate solution (30ml) and extracted with ethyl acetate (20mlX3). The combined organic phase was washed with water, brine and concentrated to give product (0.21 g) used for next step without furtherpurification. LCMS (Method D): RT = 1.25 min, M+H+ = 433.2.

Reference： [1]Patent: WO2011/77098,2011,A1 .Location in patent: Page/Page column 188-189

9
[ 330794-35-9 ]
[ 1396776-82-1 ]
[ 1396780-81-6 ]

Yield	Reaction Conditions	Operation in experiment
		[0770] Synthesis of Compound A- 14: 6-(4-(aminomethyl)phenyl)-N-((4,6-dimethyl-2- oxo- 1 ,2-dihydropyridin-3-yl)methyl)- 1 -isopropyl- 1 H-pyrazolo [3 ,4-b]pyridine-4- carboxamideCompound A- 14[0771] A solution of 6-bromo-N-((4,6-dimethyl-2-oxo-l ,2-dihydropyridin-3-yl)methyl)- l -isopropyl-lH-pyrazolo[3,4-b]pyridine-4-carboxamide (1 equiv), tert-butyl 4-(4,4,5,5- tetramethyl-l ,3,2-dioxaborolan-2-yl)benzylcarbamate (1.2 equiv.) and Pd(PPh3)4 (0.1 equiv.) in 1 ,4-dioxane was purged with argon for 10 min. Then, 2 M Na2C03 (3.6 equiv.) in water was added to it and again argon was purged through it for 10 min. The reaction mixture was stirred at 100 C for 1 h. After completion of the reaction, water was added to it and extraction was carried out using EtOAc. The combined organic layers were washed with water, dried over anhydrous Na2S04, filtered and concentrated under reduced pressure to afford crude material which was purified by column chromatography to give the Boc protected intermediate. Boc-deprotection was achieved by using TFA-DCM (10 times by volume in 1 : 1 ratio, work up using NaHC03) to give the desired compound (65% yield). LCMS: 445.15 (M + 1)+; HPLC: 99.78% (@ 254 nm), (Rt; 4.950); 1H NMR (DMSO-d6, 400 MHz) delta 1 1.52 (s, 1H), 8.91 (t, 1H), 8.36 (s, 1H), 8.31 (d, 2H, J=8 Hz), 8.21 (bs, 2H), 8.16 (s, 1H), 7.61 (d, 2H, J=8.8 Hz), 5.88 (s, 1H), 5.34-5.30 (m, 1H), 4.40 (d, 2H, J=4.4 Hz), 4.12 (d, 2H, J=5.2 Hz), 2.21 (s, 3H), 2.1 l(s, 3H), 1.53 (d, 6H, J=6.8 Hz).

Reference： [1]Patent: WO2012/118812,2012,A2 .Location in patent: Page/Page column 236-237

10
[ 330794-35-9 ]
[ 1428540-06-0 ]

Reference： [1]Chemical Communications,2013,vol. 49,p. 3110 - 3112

11
[ 330794-35-9 ]
[ 1380485-22-2 ]
[ 1428540-05-9 ]

Reference： [1]Chemical Communications,2013,vol. 49,p. 3110 - 3112

12
[ 330794-35-9 ]
3-(3,3,4,4,5,5-hexafluoro-2-(5-iodo-2-methylthiophen-3-yl)cyclopent-1-enyl)-5-iodo-2-methylthiophene [ No CAS ]
C₃₉H₄₀F₆N₂O₄S₂ [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2013,vol. 52,p. 8666 - 8670
Angew. Chem.,2013,vol. 125,p. 8828 - 8832,5

13
[ 3959-07-7 ]
[ 330794-35-9 ]

Reference： [1]Angewandte Chemie - International Edition,2013,vol. 52,p. 8666 - 8670
Angew. Chem.,2013,vol. 125,p. 8828 - 8832,5
[2]Patent: WO2015/89327,2015,A1
[3]Patent: CN108794490,2018,A

14
[ 24424-99-5 ]
[ 330794-35-9 ]

Reference： [1]Angewandte Chemie - International Edition,2013,vol. 52,p. 8666 - 8670
Angew. Chem.,2013,vol. 125,p. 8828 - 8832,5
[2]Patent: WO2015/89327,2015,A1
[3]Patent: CN108794490,2018,A

15
[ 330794-35-9 ]
[ 1532551-41-9 ]

Reference： [1]Inorganic Chemistry,2014,vol. 53,p. 1257 - 1259

16
[ 330794-35-9 ]
[ 1532551-36-2 ]

Reference： [1]Inorganic Chemistry,2014,vol. 53,p. 1257 - 1259

17
[ 330794-35-9 ]
[ 1532551-37-3 ]

Reference： [1]Inorganic Chemistry,2014,vol. 53,p. 1257 - 1259

18
[ 330794-35-9 ]
[ 162102-79-6 ]
C₂₁H₂₄N₂O₆ [ No CAS ]

Reference： [1]Inorganic Chemistry,2014,vol. 53,p. 1257 - 1259

19
[ 330794-35-9 ]
[ 3680-69-1 ]
[ 1607005-55-9 ]

Yield	Reaction Conditions	Operation in experiment
52%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,2-dimethoxyethane; water; at 150℃; for 1h;Microwave irradiation;	In a 20 mL sealable microwave tube, 4-chloro-7H-pyrrolo[2,3-d]pyrimidine (500 mg, 3.26 mmol, Eq: 1.00), tert-butyl 4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)benzylcarbamate (1.6 g, 4.8 mmol, Eq: 1.47) and potassium carbonate (1.8 g, 13.0 mmol, Eq: 4.00) were combined with DME (10 mL) and water (5 mL). Pd(PPh3)4(376 mg, 0.326 mmol, Eq: 0.1) was added and the reaction mixture was heated at 150 C for 60 minutes. The resulting solution was diluted with EtOAc and washed with brine. The combined organic phases were dried over anhydrous sodium sulfate then the solvent was removed under reduced pressure. The crude material was purified by column chromatography (silica, 5-70% ethyl acetate in hexanes). The title compound was obtained as a solid (545 mg, 52% yield). LC/MS: m/z calculated for C18H20N402([M+H]+): 325.3 Found: 325.2

Reference： [1]Patent: WO2014/64131,2014,A2 .Location in patent: Page/Page column 68; 69

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[ 1607005-15-1 ]

Reference： [1]Patent: WO2014/64131,2014,A2

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[ 330794-35-9 ]
[ 1255636-51-1 ]

Reference： [1]Patent: WO2014/64131,2014,A2
[2]Patent: WO2015/89327,2015,A1

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[ 1011717-00-2 ]
methyl 4-(4-(4-(((tert-butoxycarbonyl)amino)methyl)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-6-yl)benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In N,N-dimethyl-formamide; at 100℃; for 3h;	To a solution of methyl 4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-6-yl)benzoate (0.95 g, 3.3 mmol, 1.0 eq) in DMF (10 mL), was added tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)benzylcarbamate (1.3 g, 3.9 mmol, 1.2 eq), Pd(dppf)Cl2.DCM (0.2 g, 0.33 mmol, 0.1 eq) and K2CO3(0.9 g, 6.6 mmol, 2.0 eq). The reaction solution was stirred at 100 C for 3 h, cooled to rt and diluted with water (20 mL) and EtOAc (50 mL). The organic layer was separated and the aqueous was extracted with EtOAc (50 mL x 2). The combined organic layers were concentrated in vacuo to afford a residue which was purified by column chromatography (petroleum ether/EtOAc =1:1) to afford the title compound (0.9 g, yield: 60%). ESI-MS (M+H-56)+: 459.1.1H NMR (400 MHz, DMSO-d6) : 12.89 (s, 1H), 8.86 (s, 1H), 8.26-8.22 (m, 4H) 8.05 (d, J = 8.8 Hz, 2H), 7.64 (s, 1H), 7.55-7.52 (m, 1H), 7.48 -7.46 (m, 2H), 4.25 (d, J = 6.0 Hz, 2H), 3.89 (s, 3H), 1.40 (s, 9H).

Reference： [1]Patent: WO2015/89327,2015,A1 .Location in patent: Paragraph 0418

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[ 479633-63-1 ]
[ 1607005-81-1 ]