Name: 380430-49-9|(4-Boc-Aminophenyl)boronic acid|98%
Brand: Ambeed
SKU: A298015
Price: 5.0 USD
Availability: InStock
Rating: 99 (30 reviews)

1
[ 626-39-1 ]
[ 380430-49-9 ]
[ 876593-24-7 ]

Yield	Reaction Conditions	Operation in experiment
61%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 100℃; for 48h;Inert atmosphere;	4-[N-(tert-Butoxycarbonyl)amino]phenylboronic acid (1.00 g, 4.22 mmol) was dissolved in 5:1 dioxane/H2O mixture (60 mL), and 1,3,5-tribromobenzene (0.31 g, 1.00 mmol), Pd(dppf)Cl2 (0.20 g, 0.27 mmol), and K2CO3(0.80 g, 5.80 mmol) were added sequentially. The resulting mixture was stirred in a preheated (100 C) oil bath for 48 h under argon atmosphere. After the mixture had cooled to room temperature, it was poured into brine and extracted twice with dichloromethane. The combined organic extracts were washed three times with water, dried over anhydrous Na2SO4, filtered, and evaporated. The residue was purified using column chromatography (silica gel, petroleum ether-ethyl acetate 30:1 as eluent) to yield 0.40 g (61 %) white solid. NMR (400 MHz, CDCl3) delta 7.69 (s, 3H), 7.64 (d, J = 8.6 Hz, 6H), 7.49 (d, J = 8.4 Hz, 6H), 1.56 (s, 27H).

Reference： [1]Research on Chemical Intermediates,2018,vol. 44,p. 6445 - 6451
[2]Chemistry - A European Journal,2006,vol. 12,p. 763 - 776

2
[ 1003878-37-2 ]
[ 380430-49-9 ]
[ 1003878-15-6 ]

Yield	Reaction Conditions	Operation in experiment
45%	With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In water; N,N-dimethyl-formamide; at 80℃; for 16h;	To a solution of N-[1-(4-bromophenyl)-2-(4-morpholinyl)ethyl]-2-(6,7-dichloro-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)-N-methylacetamide (1.64 g, 2.9 mmol) and [4-([(1,1-dimethylethyl)oxy]carbonyl}amino)phenyl]boronic acid (0.77 g, 3.2 mmol) in DMF (10 mL) was added Pd(dppf)Cl2 (0.12 g, 0.15 mmol) and 2N aqueous solution of Na2CO3 (0.26 mL, 0.52 mmol). The resultant mixture was stirred at 80 C. for 16 h. The mixture was filtered through a 0.45 uM filter and concentrated under reduce pressure. The residue was dissolved in ethyl acetate (100 mL)and washed with 5% NaHCO3 (100 mL) and brine (100 mL). The organic layer was dried over MgSO4 and concentrated. The residue was recrystalized in methanol to give 0.77 g (40%) white solid. The mother liquid was concentrated and was purified by using a Gilson preparative HPLC (Phenomenex, 100×50 mm, 10 micron, 90 mL/min, A: acetonitrile B: water, A: 10 to 90% over 15 min, UV detection at 214 nm) to give 0.10 g (5%) of the title compound as yellow oil. Total yield 45%. MS (ES) m/e 669.4 [M+H]+.

Reference： [1]Patent: US2008/21023,2008,A1 .Location in patent: Page/Page column 106-107

3
[ 180995-12-4 ]
[ 380430-49-9 ]
[4-(4-chloro-3-cyanopyrid-2-yl)phenyl]carbamic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 100℃; for 2.0h;	[4-(4-Chloro-3-cyanopyrid-2-yl)phenyl]carbamic acid tert-butyl ester To a solution of 519 mg of <strong>[180995-12-4]2,4-dichloronicotinonitrile</strong> in 25.5 ml of dioxane are added 782 mg of (4-boc-aminophenyl)boronic acid, 693 mg of sodium bicarbonate in 8.5 ml of water and 347 mg of tetrakis(triphenyl-phosphine)palladium. The suspension is stirred at 100 C. for 2 hours under argon. After cooling, the reaction mixture is poured into water and extracted three times with a 90/10 ethyl acetate/methanol solution. The combined organic phases are dried over magnesium sulfate and concentrated under reduced pressure. 1.58 g of crude product are chromatographed on a prepacked Biotage KP-Sil column of 60 A SiO2 32-63 mum (from 0.5/99.5 to 1/99 gradient of solution A in dichloromethane; solution A=38/17/2 dichloromethane/methanol/aqueous ammonia). 797 mg of [4-(4-chloro-3-cyanopyrid-2-yl)phenyl]carbamic acid tert-butyl ester are obtained, the characteristics of which are as follows: MS-EI: 329 (+) IR spectrum (CCl4): 3343; 2981; 2230; 1741; 1524; 1501; 1411; 1392; 1368; 1316; 1220; 1155; 1050 and 844 cm-1 1H NMR spectrum (400 MHz, (CD3)2SO, delta in ppm): 1.50 (s, 9H); 7.62 (d, J=9.0 Hz, 2H); from 7.78 to 7.84 (m, 3H); 8.83 (d, J=5.5 Hz, 1H); 9.67 (s, 1H).

Reference： [1]Patent: US2008/39491,2008,A1 .Location in patent: Page/Page column 24

4
[ 380430-49-9 ]
[ 118727-34-7 ]

Reference： [1]Chemistry - A European Journal,2006,vol. 12,p. 763 - 776
[2]Chemistry - A European Journal,2006,vol. 12,p. 763 - 776

5
[ 944062-55-9 ]
[ 380430-49-9 ]
[ 693793-03-2 ]

Yield	Reaction Conditions	Operation in experiment
25%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In DMF (N,N-dimethyl-formamide); water; at 85℃; for 48h;	To a mixture of methyl N- (6-CHLORO-4-PYRIMIDINYL) phenylalaninate (0.49 g, 1.69 mmol), <strong>[380430-49-9]{4-[(tert-butoxycarbonyl)amino]phenyl}boronic acid</strong> (0.48 g, 2.02 mmol) and N, N dimethylformamide (10 mL) under an argon atmosphere was added 2N sodium carbonate aqueous solution (1. 69 mL, 3.37 mmol) followed by tetrakis (triphenylphosphine)- palladium (0.097 g, 0.08 mmol). The mixture was stirred at 85C for 2 day. After cooled to room temperature, the mixture was partitioned between ethyl acetate and water. The separated organic phase was washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography on silica-gel (hexane: ethyl acetate, 4: 1) to give methyl N-(6-{4-[(tert- butoxycarbonyl) amino] PYMNIDIN-4-YL) PHENYLALANINATE (0. 189 g, 25%) as color- less oil.

Reference： [1]Patent: WO2004/43926,2004,A1 .Location in patent: Page 121

6
[ 930-68-7 ]
[ 380430-49-9 ]
[ 901528-86-7 ]

Yield	Reaction Conditions	Operation in experiment
99%	With lithium hydroxide;(eta6-1,4-dihydroxybenzene)(eta2,eta2-cyclooctadiene-1,5)rhodium tetrafluoroborate; In 1,2-dimethoxyethane; water; at 50℃; for 1 - 3h;	This study demonstrates that base is required for the reaction and 2.0 mol % provides optimal yield of the desired conjugate addition product. During further studies to optimize the reaction conditions, a series of additives and bases were examined. Catalytic amounts of carbonate bases, Na2CO3 (2.0 mol %) or Cs2CO3 (2.0 mol %), are effective at producing high yielding conjugate additions with boronic acid 4a (Table 3, entries 6 & 8), while stoichiometric amounts (120 mol %) of carbonate bases (entries 7 & 9) attenuated reactivity. Pyridine, either catalytic or quantitative, arrests all reactivity and consistent with this observation is the lack of product with pyridine boronic acids. Additional hydroquinone shows no detectable effect upon reaction outcome while lithium salts, such as LiCl or LiBF4, either diminish the amount of product or completely arrest the reaction. The addition reaction can be run in the absence of organic solvent, however, stoichiometric base (120 mol %) is required for efficient reaction (entry 10 versus 11). This result is presumably due to the solubilization of the boronic acid into the aqueous phase by formation of the corresponding-ate complex. Preferred reaction conditions, outlined as a general procedure in the experimental section, are highly effective and facile for a range of boronic acid substrates. Using 2-cyclohexen-1-one as our conjugate acceptor, a number of different aryl boronic acids were studied with our optimized reaction conditions (Table 4). Ketone products 6a-g (entries 1-7) are afforded in high yields, with low catalyst loading (0.5 mol %) and low boronic acid equivalency (1.2 eq). Electron deficient boronic acids (entries 5-9) are afforded in excellent yields (94-99%) without any procedural modification from the earlier analogues. Improved yields (92-93%) of meta-nitro analogue 6i were achieved either by increasing the catalyst loading (2.0 mol %, entry 12) or increasing equivalencies of boronic acid (1.5 equiv, entry 13). Tri-fluoro analogues 6j and 6k (entry 14,15) were afforded in good to moderate yields (70% and 30% respectively). This is believed to be the first report of conjugate addition of a tri-halogenated aryl boronic acid. Efforts are underway to further optimize the additions of tri-fluorophenyl boronic acids 4j and 4k. Both 2,4-bis(trifluoromethyl)phenyl boronic acid and ortho-nitro phenyl boronic acid failed to produce the desired addition products under our standard conditions. The 4-, 5- or 6-indoloboronic acids (Table 5) undergo conjugate addition while N-Boc-2-indoloboronic acid (entry 1) does not afford any product. The additions of 4-indoloboronic acid (entry 2, Table 4) and o-tolyl boronic acid (entry 3, Table 4) show that ortho substitution can be tolerated, despite the attenuated reactivity observed for o-substituted boronic acids and documented difficulties of reactions with N-Boc protected pyrrole-2-boronic acids. See Lautens, M.; Mancuso, J.; Grover, H. Synthesis 2004, 12, 2006-2014.
99%	lithium hydroxide; (eta6-1,4-dihydroxybenzene)(eta2,eta2-cyclooctadiene-1,5)rhodium tetrafluoroborate; In 1,2-dimethoxyethane; water; at 50℃; for 1 - 3h;Conversion of starting material;	A 1-dram vial fitted with a Teflon cap was charged with aryl boronic acid (1.2 mmol) and enone (1.0 mmol) and dimethoxyethane (DME, 1.0 mL). A solution of 1 (0.02 M DME, 0.250 mL, 0.005 mmol, 0.5 mol %) followed by an aqueous LiOH solution (1.0 M, 0.020 mL, 0.020 mmol, 2.0 mol %). The headspace of the vial was flushed with N2 and deoxygenated H2O (1.5 mL) was added. The vial was capped and the resulting mixture was stirred at 50 C. for 1 h. The reaction mixture was diluted with a saturated solution of NH4Cl (5 mL), extracted with 25% EtOAc/hexanes (2×5 mL), dried (Na2SO4), filtered through a silica plug, and concentrated to afford pure product as characterized by 1H and 13C NMR and high resolution mass spectrometry. Note, it was also found that diethyl ether and THF can be used in place of DME, however no reaction is observed in toluene as solvent. ; Using 2-cyclohexen-1-one as our conjugate acceptor, a number of different aryl boronic acids were studied with our optimized reaction conditions (Table 4). Ketone products 6a-g (entries 1-7) are afforded in high yields, with low catalyst loading (0.5 mol %) and low boronic acid equivalency (1.2 eq). Electron deficient boronic acids (entries 5-9) are afforded in excellent yields (94-99%) without any procedural modification from the earlier analogues. Improved yields (92-93%) of meta-nitro analogue 6i were achieved either by increasing the catalyst loading (2.0 mol %, entry 12) or increasing equivalencies of boronic acid (1.5 equiv, entry 13). Tri-fluoro analogues 6j and 6k (entry 14,15) were afforded in good to moderate yields (70% and 30% respectively). This is believed to be the first report of conjugate addition of a tri-halogenated aryl boronic acid. Efforts are underway to further optimize the additions of tri-fluorophenyl boronic acids 4j and 4k.; Both 2,4-bis(trifluoromethyl)phenyl boronic acid and ortho-nitro phenyl boronic acid failed to produce the desired addition products under our standard conditions. The 4-, 5- or 6-indoloboronic acids (Table 5) undergo conjugate addition while N-Boc-2-indoloboronic acid (entry 1) does not afford any product. The additions of 4-indoloboronic acid (entry 2, Table 4) and o-tolyl boronic acid (entry 3, Table 4) show that ortho substitution can be tolerated, despite the attenuated reactivity observed for o-substituted boronic acids and documented difficulties of reactions with N-Boc protected pyrrole-2-boronic acids.

Reference： [1]Patent: US2007/123715,2007,A1 .Location in patent: Page/Page column 13; 14
[2]Patent: US2007/117981,2007,A1 .Location in patent: Page/Page column 9; 10; 13

7
ethyl 3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylate [ No CAS ]
[ 380430-49-9 ]
ethyl 1-[4-([(1,1-dimethylethyl)oxy]carbonyl}amino)phenyl]-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine;copper diacetate; In dichloromethane; at 20℃; for 24h;	Intermediate 33Ethyl 1 -[4-([(1 ,1 -dimethylethyl)oxy]carbonyl}amino)phenyl]-3-[[(fra/iotas-4- methylcyclohexyl)carbonyl](1-methylethyl)amino]-1H-pyrazole-4-carboxylate EPO <DP n="49"/>A solution of Intermediate 4 ( .50 g), [4-([(1 ,1-di rmethylethyl)oxy]carbonyl}amino)phenyl] boronic acid (1.66 g), copper (II) acetate (1.68 g) and pyridine (0.75 ml.) in DCM (30 ml_) was stirred at room temperature under nitrogen for 24 h. The solution was washed sequentially with aqueous sodium bicarbonate solution, water and 2M HCI, dried using a hydrophobic frit and evaporated to dryness. This crude product was purified by ISCO companion silica chromatography eluting with a gradient of ethyl acetate in cyclohexane to give the title compound. MS calcd for (C28H40N4O5 + H)+: 513 MS found (electrospray): (M+H)+ = 513

Reference： [1]Patent: WO2007/39146,2007,A1 .Location in patent: Page/Page column 47-48

8
[ 942920-42-5 ]
[ 380430-49-9 ]
[ 942920-43-6 ]

Yield	Reaction Conditions	Operation in experiment
40%	With barium dihydroxide;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 80℃; for 36h;	Intermediate 54; 1,1-dimethylethyl{4-[2-(1H-pyrrolo[2,3-b]pyridin-4-yl)-3-thienyl]phenyl}carbamate ; To a solution of 4-(3-bromo-2-thienyl)-1-[(4-methylphenyl)sulfonyl]-1H-pyrrolo[2,3-b]pyridine (5.3 mmol) in 40 mL of 1,2-dimethoxyethane was added 4-(N-Boc-amino)phenyl boronic acid (13.8 mmol), tetrakis(triphenylphosphine)palladium(0), (0.17 mmol), water (16 mL) and barium hydroxide (21.2 mmol). The reaction was heated at 80 C. for 36 h. The 1,2-dimethoxyethane was evaporated and the residue taken up in ethyl acetate and washed with water (50 mL). The crude product was purified by silica gel chromatography (0-50% ethyl acetate/hexanes) to give the title compound (40%). ESMS [M+H]+: 392.2

Reference： [1]Patent: US2007/149561,2007,A1 .Location in patent: Page/Page column 89

9
[ 55052-28-3 ]
[ 380430-49-9 ]
[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-phenyl]-carbamic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		[225] A mixture of 4-chloro-7-azaindole (2.64g, 17.4mmole) in dioxane (8OmL) and water (2OmL) in a 25OmL, two-necked round bottomed flask was charged with K2CO3 (1.42 g, 10.3 mmole), (4-BOC- aminophenyl)boronic acid (4.74g, 20mmole), and Pd^pPf)2Cl2-CH2Cl2 catalyst (685mg, 0.84mmole). Nitrogen was bubbled into the reaction mixture for 15min at it and then heated at 1000C overnight under nitrogen atmosphere. The reaction mixture was cooled to rt and added triethylamine (1OmL.) and evaporated to dryness and purified by column chromatography. The crude was taken in methylene chloride and loaded onto the column. The column was eluted with 20-30% ethyl acetate in methylene chloride and the desired fractions from column were collected and the resulting solid was triturated with hot isopropyl ether; cooled to rt and filtered to give the title compound as a pale yellow solid. 1H NMR (DMSOd6): delta 1.49 (s, 9H), 6.61 (m, IH), 7.13 (d, IH, J = 5.1 Hz), 7.5 (t, IH, J = 2.85 Hz), 7.65 (m, 4H), 8.23 (d, IH, J = 4.8 Hz), 9.53 (s, IH), 11.71 (bra, IH); MS (ES+): m/z 310.20 [MH+].

Reference： [1]Patent: WO2007/84667,2007,A2 .Location in patent: Page/Page column 55

10
[ 1279846-99-9 ]
[ 380430-49-9 ]
6-(4-tert-butoxycarbonylaminophenyl)-3-[(thiophen-3-yl)carbonylamino]-1H-indazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 90℃; for 4h;	6-(4-tert-Butoxycarbonylaminophenyl)-1-[3-(thiophen-3-yl)carbonylamino]-1H-indazole; A solution of 6 g of 6-bromo-1-[(thiophen-3-yl)carbonyl]-3-[(thiophen-3-yl)carbonylamino]indazole in 350 mL of dioxane is admixed with 4.93 g of 4-(tert-butyloxycarbonylamino)phenylboronic acid. A solution of 4.12 g of sodium carbonate in 90 mL of water is added, followed by 1.93 g of tetrakistriphenylphosphinepalladium. The reaction mixture is stirred at 90 C. for 4 hours and then poured into 120 mL of distilled water. Following extraction with ethyl acetate and then washing of the extracts with saturated sodium chloride solution, the organic phase is concentrated under reduced pressure, to give 13.18 g of a solid, which is purified by flash chromatography on a silica column (60; 35-70 muM), eluting with a cyclohexane/ethyl acetate (60/40 by volume) mixture, to give 4.2 g of 6-(4-tert-butoxycarbonylaminophenyl)-1-[3-(thiophen-3-yl)carbonylamino]-1H-indazole, whose characteristics are as follows: MS spectrum (ES+): m/z=435 [MH+]

Reference： [1]Patent: US2007/161626,2007,A1 .Location in patent: Page/Page column 7

11
butyl 4-amino-5-bromopyrrolo[2,1-f][1,2,4]triazine-7-carboxylate [ No CAS ]
[ 380430-49-9 ]
[ 939968-67-9 ]

Yield	Reaction Conditions	Operation in experiment
26%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 80℃;	A mixture of butyl 4-amino-5-bromopyrrolo[2,l-f][l,2,4]triazine-7-carboxylate (456.0 mg, 1.46 mmol), {4-[(tert-butoxycarbonyl)amino]pb.enyl}boronic acid (517.8 mg, 2.18 mmol), 2 M aqueous sodium carbonate solution (2.2 mL, 4.40 mmol), and tetrakis(triphenylphosphine)palladium(0) (168.3 mg, 0.15 mmol) in 1,2-dimethoxyethane(11 mL) was heated (80 0C) overnight. The reaction mixture was diluted with DMF and purified by HPLC using a gradient of 30 - 95% of MeCN in water to give 163.2 mg (26%) of the title compound as a white solid. 1H-NMR (DMSO-J6) delta 9.52 (s, 1 H), 8.08 (bs, 1 H), 8.06 (s, 1 H), 7.56 (d, J = 8.6 Hz, 2 H), 7.35 (d, J = 8.6 Hz, 2 H)5 7.18 (s, 1 H), 5.67 (bs, 1 H), 4.25 (t, J = 6.5 Hz, 2 H), 1.71-1.64 (m, 2 H), 1.47-1.37 (m, 2 H), 0.93 (t, / = 7.4, 3 H);MS [M+Hf = 426.2; LCMS RT = 3.43 min.

Reference： [1]Patent: WO2007/64931,2007,A2 .Location in patent: Page/Page column 263-264

12
6-bromo-3-[(thiophen-3-yl)carbonylamino]-4,5,7-trifluoro-1H-indazole [ No CAS ]
[ 380430-49-9 ]
6-(4-tert-butoxycarbonylaminophenyl)-3-[(thiophen-3-yl)carbonylamino]-4,5,7-trifluoro-1H-indazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 90℃; for 42h;	6-(4-tert-Butoxycarbonylaminophenyl)-1-[3-(thiophen-3-yl)carbonylamino]-4,5,7-trifluoro-1H-indazole; A solution of 0.5 g of 6-bromo-1-[3-[(thiophen-3-yl)carbonylamino]-4,5,7-trifluoro-1H-indazole in 40 mL of dioxane is admixed with 0.31 g of 4-(tert-butyloxycarbonylamino)phenylboronic acid. A solution of 0.42 g of sodium carbonate in 5 mL of water is added, followed by 0.184 g of tetrakistriphenylphosphinepalladium. The reaction mixture is stirred at 90 C. for 42 hours and then poured into 40 mL of distilled water. Following extraction with dichloromethane and then washing with saturated sodium chloride solution, the organic phase is concentrated under reduced pressure, to give a solid which is purified by flash chromatography on a silica column (60; 35-70 muM), eluting with a cyclohexane/ethyl acetate (50/50 by volume) mixture, to give 0.65 g of 6-(4-tert-butoxycarbonylaminophenyl)-1-[3-(thiophen-3-yl)carbonylamino]-4,5,7-trifluoro-1H-indazole, whose characteristics are as follows: MS spectrum (ES+): m/z=489 [MH+]

Reference： [1]Patent: US2007/161626,2007,A1 .Location in patent: Page/Page column 11-12

13
methyl 3-{(cyclopropylmethyl)[(trans-4-methylcyclohexyl)carbonyl]amino}-5-iodo-2-thiophenecarboxylate [ No CAS ]
[ 380430-49-9 ]
methyl 3-{(cyclopropylmethyl)[(trans-4-methylcyclohexyl)carbonyl]amino}-5-[4-([(1,1-dimethylethyl)oxy]carbonyl}amino)phenyl]-2-thiophenecarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 100℃; for 2h;	[4-([(1 ,1-Dimethylethyl)oxy]carbonyl}amino)phenyl]boronic acid (1.23 g), Intermediate 62 (2 g) and sodium carbonate (1.84 g) were dissolved in DMF (30 ml.) and water (5 ml_). Tetrakis(triphenylphosphine)palladium(0) (0.50 g) was added and the reaction mixture was stirred at 1000C under nitrogen for 2 h. The reaction mixture was evaporated in vacuo and was partitioned between DCM and water. The aqueous layer was washed with DCM (2 x -25 ml_), the organic phase was combined, dried by passing through a hydrophobic frit and evaporated in vacuo. The crude material was loaded onto a 330 g silica ISCO cartridge eluting with a gradient of 5 - 100% EtOAc in cyclohexane to give the title compound. MS calcd for (C29H38N2O5S + H)+ : 527 MS found (electrospray) : (M+H)+ = 527

Reference： [1]Patent: WO2008/59042,2008,A1 .Location in patent: Page/Page column 68

14
methyl 5-iodo-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-2-thiophenecarboxylate [ No CAS ]
[ 380430-49-9 ]
methyl 5-[4-([(1,1-dimethylethyl)oxy]carbonyl}amino)phenyl]-3-[[(trans-4-methylcyclohexyl)carbonyl](1-methylethyl)amino]-2-thiophenecarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 100℃; for 3h;	A mixture of Intermediate 7 (3.5 g), [4-([(1 ,1- dimethylethyl)oxy]carbonyl}amino)phenyl]boronic acid (2.0 g), sodium carbonate (3.3 g, dissolved in water 20 ml_), and tetrakis(triphenylphosphine)palladium(0) (900 mg) were dissolved in DMF (100 ml.) and the reaction mixture was stirred at 1000C for 3 h. The mixture was evaporated in vacuo and the residue partitioned between water and DCM. The organic layer was washed with water (x 2), dried using a hydrophobic frit and evaporated in vacuo. The crude material was purified by ISCO Companion silica chromatography, eluting with a gradient 5-50% EtOAc in cyclohexane to give the title compound. MS calcd for (C28H38N2O5S + H)+: 515 MS found (electrospray): (M+H)+ = 515

Reference： [1]Patent: WO2008/59042,2008,A1 .Location in patent: Page/Page column 43

15
[ 69190-56-3 ]
[ 380430-49-9 ]
[ 1044210-28-7 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydroxide; 4-(1,1-dimethylethyl)benzoic acid;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; for 12h;Heating / reflux;	[0501] Experimental Details: To a stirred and degassed mixture of compound 2 (4.11 g, 0.02 mol) and compound 3 (4.74 g, 0.02 mol), and KOH (5.28 g, 0.1 mol) and TBBA (6.44 g, 0.02 mol) in anhydrous THF (100 mL) was added Pd (PPh3)4 (2.31 g, 2 mmol) under N2 atmosphere and stirred under reflux for 12 h. After filtrating off the solid, the filtrate was concentrated to dryness. The residue was purified by column to give the product 4.
	With terephthal-bis-4-n-butylaniline; potassium hydroxide;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; for 12h;Inert atmosphere; Reflux;	Experimental Details: To a stirred and degassed mixture of compound 2 (4.11 g, 0.02 mol) and compound 3 (4.74 g, 0.02 mol), and KOH (5.28 g, 0.1 mol) and TBBA (6.44 g, 0.02 mol) in anhydrous THF (100 mL) was added Pd (PPh3)4 (2.31 g, 2 mmol) under N2 atmosphere and stirred under reflux for 12 h. After filtrating off the solid, the filtrate was concentrated to dryness. The residue was purified by column to give the product 4.

Reference： [1]Patent: WO2008/91681,2008,A2 .Location in patent: Page/Page column 233-234
[2]Patent: US2010/16298,2010,A1 .Location in patent: Page/Page column 197

16
[ 1101817-58-6 ]
[ 380430-49-9 ]
C₂₄H₃₂N₄O₅S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,2-dimethoxyethane; ethanol; water; N,N-dimethyl-formamide; at 80℃; for 2h;	To a solution of 2-chloro-4-[(3S)-3-methylmorpholin-4-yl]-6-(1-methylsulfonylcyclopropyl)pyrimidine (1.52 g, 4.58 mmol) in DMF (0.24 mL), DME (9.33 mL), water (4.0 mL) and ethanol (2.67 mL) was added 4-(tert-butoxycarbonylamino)phenylboronic acid (1.629 g, 6.87 mmol), sodium carbonate (5.73 mL, 11.45 mmol), and dichlorobis(triphenylphosphine)palladium(II) (0.161 g, 0.23 mmol) and the suspension heated at 80 C. for 2 hours. The reaction mixture was cooled to RT, diluted with ethyl acetate (10 mL) and washed with water (10 mL). The organic layer was dried (MgSO4), filtered and evaporated. The crude product was dissolved in DCM (6.67 mL) and trifluoroacetic acid (0.353 mL, 4.58 mmol) added and the reaction was stirred at RT for 16 hours. The crude product was purified by flash silica chromatography, elution gradient 0 to 10% (7.5N ammonia in methanol) in DCM, to give the desired material as a beige solid (1.283 g). NMR Spectrum: 1H NMR (400.132 MHz, DMSO) delta 1.24 (3H, d), 1.55 (2H, m), 1.67 (2H, m), 3.23 (1H, m), 3.27 (3H, s), 3.47 (1H, m), 3.63 (1H, m), 3.77 (1H, d), 3.97 (1H, m), 4.24 (1H, s), 4.58 (1H, s), 5.75 (1H, s), 6.68 (2H, d), 8.04 (2H, d) LCMS Spectrum: m/z (ESI+) (M+H)+=389; HPLC tR=1.82 min.

Reference： [1]Patent: US2009/18134,2009,A1 .Location in patent: Page/Page column 127

17
[ 1009627-11-5 ]
[ 380430-49-9 ]
[ 1009627-10-4 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,2-dimethoxyethane; ethanol; water; N,N-dimethyl-formamide; at 90℃; for 5h;	tert-Butyl N- [4- [4- [(36^-3 -methylmorpholin-4-yll-6-(methylsulfonylmethyl)pyrimidin-2- yllphenyll carbamate2-Chloro-4-[(35)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine (1.0 g, 3.27 mmol) was dissolved in a solution of 18% DMF in a mixture of 7:3:2DME:water:ethanol (7 mL). [4-[(2-Methylpropan-2-yl)oxycarbonylamino]phenyl]boronic acid (1.165 g, 4.91 mmol), 2M sodium carbonate solution (4 mL) and dichlorobis(triphenylphosphine) palladium catalyst (115 mg, 0.16 mmol) were then added to the solution and refluxed at 900C for 5 hours under nitrogen atmosphere. The reaction was allowed to cool to room temp then partitioned between ethyl acetate and water. The organics were dried over magnesium sulphate, filtered and concentrated to dryness. The crude oil was dissolved in dichloromethane and filtered to remove insoluble material. A beige solid precipitated from the filtrates and the filtrates were filtered again. The solid was analysed and found to be the excess boronic acid and the filtrates contained the product and some impurities. The filtrates were purified by chromatography on silica, eluting with 0-40% ethyl acetate in isohexane, to give the desired compound as an orange oil (530 mg). LCMS Spectrum: MH+ 463, retention time 2.23 min, Method 5 Min Acid
	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,2-dimethoxyethane; ethanol; water; N,N-dimethyl-formamide; at 90℃; for 5h;	2-Chloro-4-[(35)-3-methylmorpholin-4-yl]-6-(methylsulfonylmethyl)pyrimidine (1.0 g, 3.27 mmol) was dissolved in a solution of 18% DMF in a mixture of 7:3:2DME:water:ethanol (7 mL). [4-[(2-Methylpropan-2-yl)oxycarbonylamino]phenyl]boronic acid (1.165 g, 4.91 mmol), 2M sodium carbonate solution (4 mL) and dichlorobis(triphenylphosphine) palladium catalyst (115 mg, 0.16 mmol) were then added to the solution and refluxed at 900C for 5 hours under nitrogen atmosphere. The reaction was allowed to cool to room temp then partitioned between ethyl acetate and water. The organics were dried over magnesium sulphate, filtered and concentrated to dryness. The crude oil was dissolved in dichloromethane and filtered to remove insoluble material. A beige solid precipitated from the filtrates and the filtrates were filtered again. The solid was analysed and found to be the excess boronic acid and the filtrates contained the product and some impurities. The filtrates were purified by chromatography on silica, eluting with 0-40% ethyl acetate in isohexane, to give the desired compound as an orange oil (530 mg). LCMS Spectrum: MH+ 463, retention time 2.23 min, Method 5 Min Acid

Reference： [1]Patent: WO2009/7749,2009,A2 .Location in patent: Page/Page column 110
[2]Patent: WO2009/7750,2009,A1 .Location in patent: Page/Page column 111

18
[ 996-35-0 ]
[ 298-12-4 ]
[ 380430-49-9 ]
[ 1133434-03-3 ]

Yield	Reaction Conditions	Operation in experiment
62%	In toluene at 20℃; for 168h;	5 EXAMPLE 5 2-[4-(tert-Butoxycarbonylamino)phenyl]-2-[isopropyl(methyl)amino]acetic Acid (25); A 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer was charged with glyoxylic acid (618 mg, 6.72 mmol), toluene (20 mL), N,N-isopropylmethylamine (486 mg, 6.60 mmol) and 4-(tert-butoxycarbonylamino)phenylboronic acid (1.58 g, 6.66 mmol). The reaction was sealed with a plastic cap under a nitrogen atmosphere and stirred at room temperature for 7 d. After this time, the reaction was concentrated under reduced pressure. The resulting residue was subjected to flash chromatography to afford 25 in 62% yield (1.34 g) as a light brown solid: mp 320° C. dec, 1H NMR (300 MHz, DMSO-d6) δ 9.42 (s, 1H), 7.42 (d, 2H, J=8.7 Hz), 7.37 (d, 2H, J=8.7 Hz), 4.23 (s, 1H), 3.28 (m, 1H), 3.17 (s, 1H), 2.23 (s, 3H), 1.47 (s, 9H), 1.15 (d, 3H, J=6.6 Hz), 1.11 (d, 3H, J=6.6 Hz); MS (ESI+) m/z 323 (M+H).

Reference： [1]Current Patent Assignee: GILEAD SCIENCES INC - US2009/82330, 2009, A1 Location in patent: Page/Page column 33

19
[ 996-35-0 ]
[ 453-17-8 ]
[ 380430-49-9 ]
[ 1133434-00-0 ]

Yield	Reaction Conditions	Operation in experiment
69%	In ethanol; at 20℃; for 72h;	EXAMPLE 4 tert-Butyl 4-((1S,2S)-2,3-dihydroxy-1-isopropyl(methyl)amino)propyl)-phenylcarbamate (21); A 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer was charged with D-(+) glyceraldehyde (90% purity, 1.62 g, 16.2 mmol), ethanol (16 mL), N,N-methylisopropylamine (1.19 g, 16.3 mmol) and 4-(tert-butoxycarbonylamino)-phenylboronic acid (3.85 g, 16.2 mmol). The flask was sealed with a teflon stopper, and the reaction mixture was stirred for 3 d. After this time the mixture was evaporated to dryness under reduced pressure. The residue was dissolved in 10 mL of 2M aqueous sodium hydrogensulfate (20.0 mmol). The resulting solution was extracted with methyl tert-butyl ether (2×150 mL), and the aqueous layer was basified by adding potassium carbonate (2.76 g, 20.0 mmol). The suspension was extracted with ether (2×50 mL), and the organic extracts were combined and dried over sodium sulfate. After removing the drying agent by filtration, the solution was evaporated under reduced pressure to afford a 69% yield (3.79 g) of 21 as a white solid: mp 61-80 C.; 1H NMR (300 MHz, DMSO-d6) delta 9.23 (br s, 1H), 7.33 (d, 2H, J=8.4 Hz), 7.16 (d, 2H, J=8.5 Hz), 4.58 (t, 1H, J=5.3 Hz), 4.22 (d, 1H, J=4.7 Hz), 3.96 (quintet, 1H, J=5.4 Hz), 3.49 (d, 1H, J=6.2 Hz), 3.30 (m, 1H), 3.15 (m, 1H), 2.83 (septet, 1H, J=6.5 Hz), 2.06 (s, 3H), 1.47 (s, 9H), 0.85 (d, 3H, J=6.6 Hz), 0.79 (d, 3H, J=6.5 Hz); MS (ESI+) m/z 339 (M+H).

Reference： [1]Patent: US2009/82330,2009,A1 .Location in patent: Page/Page column 30-31

20
[ 1155287-45-8 ]
[ 380430-49-9 ]
[ 1155287-46-9 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate;palladium diacetate; triphenylphosphine; In toluene; at 90℃; for 7h;	A suspension of (40) (110 mg, 0.194 mmole), potassium phosphate (46 mg, 0.194 mmole), boronic acid (51 mg, 0.213 mmole) in 1.5 ml dry toluene was degassed for 10 min using argon, then palladium acetate (4.5 mg, 0.1 eq.) and triphenyl phosphine (20 mg, 0.2 eq.) were added and the mixture was heated at 90 C. for 7 hours. The reaction mixture was cooled to room temperature, diluted with 2 ml water and extracted with ethylacetate (3×5 ml). Combined organic layers were washed with water, brine, dried over sodium sulfate, filtered and concentrated. The residue was purified by prep TLC using 4% MeOH/methylene chloride to obtain 55 mg product (41). 1H-NMR-(400 MHz, CDCl3)

Reference： [1]Patent: US2009/130076,2009,A1 .Location in patent: Page/Page column 26; 27

21
[ 1155287-80-1 ]
[ 380430-49-9 ]
[ 1155287-81-2 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate;palladium diacetate; triphenylphosphine; In toluene; at 95℃; for 5h;	A suspension of (80) (200 mg, 0.39 mmole), potassium phosphate (91 mg, 0.429 mmole), boronic acid (102 mg, 0.429 mmole) in 4 mL dry toluene was degassed for 10 min using argon, then palladium acetate (5 mg, 5% eq.) and triphenyl phosphine (21 mg, 20% eq.) were added and the mixture was heated at 90 C. for 5 hours. The reaction mixture was cooled to room temperature, diluted with water and extracted with ethylacetate. Combined organic layers were washed with water, brine, dried over sodium sulfate, filtered and concentrated. The residue was purified by prep TLC using 5% MeOH/methylene chloride to obtain 120 mg product (81). 1H-NMR (400 MHz, CDCl3)

Reference： [1]Patent: US2009/130076,2009,A1 .Location in patent: Page/Page column 39

22
[ 1154417-84-1 ]
[ 380430-49-9 ]
[ 1154417-85-2 ]

Yield	Reaction Conditions	Operation in experiment
20%	With potassium phosphate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; ethanol; water; at 80℃; for 4h;	A mixture of 4-bromomethyl-2-(3-chloro-phenoxy)-1-methoxy-benzene (14) (0.33 g, 1 mmol) and 4-boc aminophenylboronic acid (0.24 g, 1.3 mmol) in DME/EtOH/H2O (4/1/1, 12 ml) was added potassium phosphate (0.46 g, 2.2 mmol) and tetrakis(triphenylphosphine)palladium (0) (120 mg, 0.1 mmol) under nitrogen. The reaction mixture was heated to 80 C for 4 h. The reaction was diluted with water, extracted with ethyl acetate, washed with water and brine, and dried over Na2SO4. After it was concentrated in vacuo, the residue was purified by chromatography on silica gel to yield 80 mg (20%) of the N-Boc protected intermediate. N-Boc de-protection and subsequent formation of HCl salt was obtained using 2N HCl in ether. The desired product P-07 was obtained in 60 mg (70% yield) as HCl salt.

Reference： [1]Patent: US2009/131530,2009,A1 .Location in patent: Page/Page column 15

23
[ 104-92-7 ]
[ 380430-49-9 ]
[ 848853-68-9 ]
[ 1137-77-5 ]

Yield	Reaction Conditions	Operation in experiment
1: 79% 2: 15%	With palladium diacetate; potassium carbonate In tetrahydrofuran; water for 12h; Inert atmosphere; Reflux;

Reference： [1]Razler, Thomas M.; Hsiao, Yi; Qian, Feng; Fu, Ruiling; Khan, Rana Kashif; Doubleday, Wendel [Journal of Organic Chemistry, 2009, vol. 74, # 3, p. 1381 - 1384]

24
[ 1155877-73-8 ]
[ 380430-49-9 ]
[ 1155877-74-9 ]

Yield	Reaction Conditions	Operation in experiment
91%	With potassium carbonate;bis(eta3-allyl-mu-chloropalladium(II)); 1,5-bis-(diphenylphosphino)pentane; In N,N-dimethyl-formamide; at 80℃; for 34h;	Synthesis of [4-(3'-Acetyl-2-fluoro-6-methoxy-biphenyl-3-ylmethyl)-phenyl]-carbamic acid tert-butyl ester In an 8 mL vial equipped with a stir bar was placed Int-7 (295 mg, 0.888 mmol), 4-[(tert-butoxycarbonyl)amino]-phenylboronic acid (232 mg, 0.977 mmol), potassium carbonate (270 mg, 1.95 mmol), 1,5-bis(diphenylphosphino)pentane (39.1 mg, 0.0888 mmol), allylpalladium(II) chloride dimer (16.2 mg, 0.0444 mmol) and dimethylformamide (1.5 mL). The reaction mixture was heated to 80 C. for 17 hours. In order to consume residual Int-7, additional allylpalladium(II) chloride dimer (32.5 mg, 0.0888 mmol) and 1,5-bis(diphenylphosphino)pentane (78.2 mg, 0.178 mmol) were added and the reaction mixture was allowed to stir at 80 C. for 17 hours. The reaction mixture was filtered through Celite and to the filtrate was added water (40 mL) and a saturated ammonium chloride solution (40 mL). After an extraction with ethyl acetate (2*50 mL), the organic portions were combined, washed with brine (50 mL), dried (MgSO4) and concentrated. The crude material was purified by column chromatography utilizing 30% EtOAc/hexanes as the eluent to produce 365 mg of Int-8 as a pale yellow solid in 91% yield.

Reference： [1]Patent: US2009/136473,2009,A1 .Location in patent: Page/Page column 25

25
[ 37159-60-7 ]
[ 380430-49-9 ]
[ 1101173-96-9 ]

Reference： [1]Organic Letters,2009,vol. 11,p. 5666 - 5669

26
2-bromo-5-(oct-1-enyl)pyridine [ No CAS ]
[ 380430-49-9 ]
[ 1218817-98-1 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate;tris-(dibenzylideneacetone)dipalladium(0); johnphos; In toluene; at 80℃;Sealed vial; Microwave irradiation;	A suspention of 4-(tert-butoxycarbonylamino)phenylboronic acid (1.19g, 5.0 mmol), 2-bromo-5-(oct-1-enyl)pyridine (LXVIII) (1.40 g, 5.5 mmol), K3PO4 (2.12g, lO.Ommol), Pd2(dba)3 (0.069g, 0.075mmol), biphenyl-2-yldi-tert-butylphosphine (0.12g, 0.375mmol) in 5 mL of toluene was sealed in a microwave reaction vial (2OmL) and the mixture was heated at 8OC overnight. The mixture was then diluted with EtOAc (100 mL) and washed with water, brine, dried over sodium sulfate. After removal of solvent the residue was chromatographed to give 1.52g of yellowish oil, tert-butyl 4-(5-(hept-1-enyl)pyridin-2-yl)phenylcarbamate. 1H NMR(CDCl3): 8.60(s, 1H), 8.00-7.90(m, 2H), 7.70-7.58(m, 2H), 7.65-7.58(m, 2H), 6.60(s, 1H), 6.40-6.28(m, 1H), 5.80-5.70(m, 1H), 2.40-2.12(m, 2H), 1.60-1.45(m, HH), 1.40-1.28(m, 4H), 0.90-0.80(m, 3H).

Reference： [1]Patent: WO2010/33701,2010,A2 .Location in patent: Page/Page column 147-148

27
(4s)-4-(5-bromothiazol-2-yloxy)-1-azatricyclo[3.3.1.13,7]decane N-borane complex [ No CAS ]
[ 380430-49-9 ]
4-{2-[(4s)-1-azatricyclo[3.3.1.13,7]dec-4-yloxy]-1,3-thiazol-5-yl}aniline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		In a sealed tube were combined the product of Example 20A (50 mg, 0.152 mmol), 4-(tert-butoxycarbonylamino)phenylboronic acid (46.8 mg, 0.198 mmol), bis(triphenylphosphine)-palladium(II) chloride (4.3 mg, 6.08 mumol), and aqueous sodium carbonate (1.0 M, 0.38 mL), followed by 2-propanol ( 1.2 mL . The tube was heated to 93 C for 90 minutes. After cooling to room temperature, the mixture was partitioned between ethyl acetate (2 x 50 mL) and water (50 mL) . The combined organic extracts were washed with brine, dried (sodium sulfate) and concentrated under reduced pressure. The resulting material was purified by preparative HPLC on a Waters Nova-Pak HR C18 6mum 60A Prep-Pak cartridge column (40mm x 100mm) <n="159"/>using a gradient of 10% to 100% acetonitrile in 10 mM aqueous ammonium acetate over 12 minutes at a flow rate of 70 mL/minute to provide a white solid. The solid was then processed as described in Method C to provide the free base It was then reacted with HCl-dioxane according to Method H to provide the titled compound: 1H NMR (500 MHz, methanol-D4) delta ppm 1.91 - 2.04 (m, 2 H), 2.21 (br s, 1 H), 2.28 - 2.39 (m, 2 H), 2.66 (br s, 2 H), 3.59 (bi s, 2 H), 3.62 - 3.75 (m, 4 H), 5 40 (t, J=3.3 Hz, 1 H), 7.17 - 7.30 (m, 2 H), 7.45 (s, 1 H), 7.52 - 7.63 (m, 2 H). MS (ESI) m/z = 328 (M+H)+.

Reference： [1]Patent: WO2008/58096,2008,A2 .Location in patent: Page/Page column 157-158

28
[ 1188914-98-8 ]
[ 380430-49-9 ]
[ 1246203-33-7 ]

Yield	Reaction Conditions	Operation in experiment
71%	With potassium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; for 1h;Inert atmosphere; Reflux;	A mixture of 1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazole (Example 2), 4-[(tert-butoxycarbonyl)amino]phenylboronic acid (90 mg, 0.380 mmol), PdCl2(dppf) (10.3 mg, 0.0126 mmol) and aq. K2CO3 (2M, 2 mL) in 1,4-dioxane (10 mL) was refluxed under nitrogen for 1 hr. The mixture was cooled to room temperature and diluted with H2O, and the aqueous phase was extracted with CH2Cl2 (3×). The combined organic extracts were dried (Na2SO4) and the solvent was removed under vacuum. Chromatography on alumina, eluting with CH2Cl2, followed by recrystallization from CH2Cl2/MeOH/hexanes gave tert-butyl 4-[4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-1,3,5-triazin-2-yl]phenylcarbamate (99 mg, 71%): mp (CH2Cl2/MeOH/hexanes) 188-190 C.; 1H NMR (CDCl3) delta 8.41 (d, J=8.8 Hz, 2H), 8.08 (dd, J=8.4, 0.6 Hz, 1H), 7.62 (t, JHF=53.4 Hz, 1H), 7.52 (d, J=8.8 Hz, 2H), 7.41 (t, J=8.2 Hz, 1H), 6.86 (d, J=7.7 Hz, 1H), 6.69 (s, 1H), 4.12 (m, 2H), 4.07 (s, 3H), 3.99 (m, 2H), 3.85 (m, 4H), 1.55 (s, 9H); Anal. Calcd. for C27H29F2N7O4: C, 58.6; H, 5.3; N, 17.2; Found: C, 58.5; H, 5.0; N, 17.7%.

Reference： [1]Patent: US2010/249099,2010,A1 .Location in patent: Page/Page column 82

29
[ 905963-29-3 ]
[ 380430-49-9 ]
[ 1013656-22-8 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine;copper diacetate; In dichloromethane; at 20℃;Molecular sieve;	Scheme IXSynthesis of a Compound of Formula XXXIXA compound of Formula XXXV (0.701 mmole), copper II acetate (0.701 mmole), 4-(n-butoxycarbonyl)aminophenyl boronic acid (1.4 mmole), 4 A molecular sieves were taken together in dichloromethane. Tri ethyl amine (3.505 mmole) was added to the reaction mixture and stirred together at room temperature over-night. The reaction mixture was then filtered through celite pad. The organic solvent was evaporated under reduced pressure, diluted with ethyl acetate, washed with saturated sodium bicarbonate solution followed by brine solution, dried over anhydrous sodium sulphate and concentrated under reduced pressure. The crude mixture was purified by column chromatography.The following compounds were prepared by following the above procedure tert-butyl {4-[2-(Difluoromethoxy)-5-(1,7-dioxa-2-azaspiro[4.4]non-2-en-3-yl)phenoxy]phenyl}carbamate (Compound No. 125);Mass (m/z): 477.07 (M++1).

Reference： [1]Patent: US2011/21473,2011,A1 .Location in patent: Page/Page column 24

30
[ 73583-37-6 ]
[ 380430-49-9 ]
[ 1268621-54-0 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,4-dioxane; water; at 70℃; for 2h;Inert atmosphere;	tert-butyl (4-(2-chloropyridin-4-yl)phenyl)carbamate To a mixture of (4-boc-aminophenyl)boronic acid (200 mg, 0.84 mmol) and 2-chloro-4-bromopyridine (162 mg, 0.84 mmol) in 10 ml of 1,4-dioxane, was added PdCl2(PPh3)2 (10 mg, 0.014 mmol) and 1M Na2CO3 aqueous solution (0.5 ml, 1.0 mmol). The mixture was heated at 70 C. under N2 for 2 hours, cooled to room temperature and poured into 100 ml of water. The brown precipitates were filtered, washed with water and dried to give tert-butyl (4-(2-chloropyridin-4-yl)phenyl)carbamate as the crude product.
	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In 1,4-dioxane; water; at 70℃; for 2h;Inert atmosphere;	tert-butyl (4-(2-chloropyridin-4-yl)phenyl)carbamateTo a mixture of (4-boc-aminophenyl)boronic acid (200mg, 0.84mmol) and 2-chloro-4- bromopyridine (162mg, 0.84mmol) in 10ml of 1,4-dioxane, was added PdCl2(PPh3)2 (10mg, 0.014mmol) and 1M Na2CO3 aqueous solution (0.5ml, 1.0mmol). The mixture was heated at 70 C under N2 for 2 hours, cooled to room temperature and poured into 100ml of water. The brown precipitates were filtered, washed with water and dried to give tert-butyl (4-(2- chloropyridin-4-yl)phenyl)carbamate as the crude product.

Reference： [1]Patent: US2011/53905,2011,A1 .Location in patent: Page/Page column 104
[2]Patent: WO2015/69287,2015,A1 .Location in patent: Page/Page column 173; 174

31
[ 709652-82-4 ]
[ 380430-49-9 ]
[ 1267853-94-0 ]

Yield	Reaction Conditions	Operation in experiment
71%		To a microwave reaction vessel were added 4-(tert- butoxycarbonylamino)phenylboronic acid (180 mg, 0.759 mmol), 5-bromo-3-cyano- 2-aminopyridine (170.0 mg, 0.858 mmol), 1,4-dioxane (3.5 mL) and 2M aqueous sodium carbonate (0.94 mL, 1.88 mmol). Argon gas was bubbled through the solution for 5 min, then tetrakis(triphenylphosphine) palladium(O) (40.0 mg, 0.035 mmol) was <n="120"/>added and the vial was sealed and heated in a microwave reactor for 20 min at 170 C. The mixture was partitioned between EtOAc (10 mL) and saturated sodium bicarbonate (10 mL) The aqueous layer was separated and extracted with ethyl acetate (3 x 10 mL). The combined organic layers were washed with brine (10 mL), dried over MgS04, filtered and concentrated under reduced pressure to give an oil which was purified by silica gel flash chromatography, eluting with 25-100% EtOAc in hexanes. The purified material was dissolved in DCM (4 mL), excess TFA (2 mL) added and the mixture was stirred at rt for 4 h. The mixture was concentrated to dryness, then EtOAc (8 mL), saturated NaHC03 (8 mL) and 1 M aqueous NaOH (1 mL) were added. After confirming basic pH, the layers were shaken and separated and the aqueous layer was extracted with EtOAc (2 x 5 mL). The combined extracts were dried over MgS04, filtered and concentrated under reduced pressure to give 2- amino-5-(4-aminophenyl)nicotinonitrile (113.9 mg, 71%) as a solid, which was sufficiently pure for the next step. LC-MS (ESI) m/z 2 (M +H)+.

Reference： [1]Patent: WO2011/22473,2011,A1 .Location in patent: Page/Page column 118-119

32
[ 709652-82-4 ]
[ 380430-49-9 ]
[ 1267849-53-5 ]

Reference： [1]Patent: WO2011/22473,2011,A1

33
C₁₂H₁₃BrN₂O₂ [ No CAS ]
[ 380430-49-9 ]
[ 1267855-07-1 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 170℃; for 0.3h;Inert atmosphere; microwave reactor;	To a microwave reaction vessel were added 4-(tert- butoxycarbonylamino)phenylboronic acid (540 mg, 2.28 mmol), 5-(4-bromophenyl)- 2-(3-(tetrahydro-2H-pyran-2-yloxy)prop-l-ynyl)pyrimidine (694 mg, 2.33 mmol), 1,4-dioxane (10 mL), and 2M aq sodium carbonate (2.5 mL, 4.91 mmol). Argon gas was bubbled through the solution for 5 min, then tetrakis(triphenylphosphine) palladium(O) (120 mg, 0.10 mmol) was added, and the the vial was sealed and heated in a microwave reactor at 170 C for 18 min, whereupon analysis by LC-MS indicated the presence of desired product. The mixture was concentrated under reduced pressure and the residue was purified by silica gel flash chromatography, eluting with 1-12% MeOH in DCM, to give impure tert-butyl 4-(2-(3-(tetrahydro-2H-pyran-2- yloxy)prop-l-ynyl)pyrimidin-5-yl)phenylcarbamate. This material was dissolved in EtOH (30 mL), 10%> Pd/C (250 mg) was added, and the resulting mixture was stirred under a hydrogen balloon at 60 C for 2 h, whereupon analysis by LC-MS showed the <n="163"/>presence of desired product. The mixture was filtered through Celite, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel flash chromatography eluting with 5-60% EtOAc in hexanes to give tert-butyl 4-(2-(3- (tetrahydro-2H-pyran-2-yloxy)propyl)pyrimidin-5-yl)phenylcarbamate (208.2 mg, 22%). LC-MS (ESI) m/z 414 (M +H)+.

Reference： [1]Patent: WO2011/22473,2011,A1 .Location in patent: Page/Page column 161-162

34
[ 1276129-46-4 ]
[ 380430-49-9 ]
[ 1276129-49-7 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; N,N-dimethyl-formamide; at 100℃;	To a slurry of 34 (300 mg, 0.85 mmol), [4-(tert-butoxycarbonylamino)-phenyl]boronic acid (260 mg, 1.1 mmol) and Pd(PPh3)4 (125 mg) in DMF (5 mL) was added aq. sat'd. Na2CO3 (3 mL). The reaction mixture was stirred at 100 C. until all starting material was consumed (ca. 30 min). The reaction mixture was cooled to RT, quenched with H2O, extracted with EtOAc, dried (Na2SO4) and concentrated. The crude product was purified by SiO2 chromatography eluting with a Magic/DCM gradient (2% to 30% Magic) to afford 250 mg of 38a.In some cases, after quenching the reaction mixture, the product precipitated after the reaction was quenched with H2O. In these cases, the precipitate was collected, and the supernatant was extracted with EtOAc, dried (Na2SO4) and subjected to SiO2 chromatography.

Reference： [1]Patent: US2011/70190,2011,A1 .Location in patent: Page/Page column 28

35
[ 947248-68-2 ]
[ 380430-49-9 ]
[ 1309593-62-1 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;bis-triphenylphosphine-palladium(II) chloride; triphenylphosphine; In propan-1-ol; for 4h;Reflux;	Intermediate [Example Int4.1 tert-butyl [4-(2-amino[1 ,2,4]triazolo[1 ,5-a]pyridin-6-yl)phenyl]carbamateTo a stirred solution of Int1.2 (5.82 g) in 1 -propanol (400 ml) was added 2M potassium carbonate solution (41 ml), {4-[(tert-butoxycarbonyl) amino] phenyl} boronic acid (8.6 g), triphenylphosphine (150 mg) and PdCl2(PPh3)2 (1 .9 g). The mixture was heated to reflux for 4h, the solvent was removed in vacuum, water (150 mL) was added and the mixture was extracted with ethyl acetate (500 mL). The organic phase was dried (sodium sulfate), filtered through Celite and the solvent was removed in vacuum. The residue was triturated with DCM to give the title compound as a white solid. Yield: 7.2 g.1 H-NMR (400MHz, DMSO-d6): delta [ppm]= 1 .37 - 1 .55 (m, 9H), 5.99 (s, 2H), 7.36 (dd, 1 H), 7.48 - 7.55 (m, 2H), 7.55 - 7.62 (m, 2H), 7.69 (dd, 1 H), 8.78 (dd, 1 H), 9.44 (s, 1 H).
	With potassium carbonate;bis-triphenylphosphine-palladium(II) chloride; triphenylphosphine; In propan-1-ol; for 4h;Reflux;	Intermediate Example Int4.1tert-butyl [4-(2-amino[1 ,2,4]triazolo[1 ,5-a]pyridin-6-yl)phenyl]carbamateTo a stirred solution of Int1.2 (5.82 g) in 1 -propanol (400 ml) was added 2M potassium carbonate solution (41 ml), (4-[(tert-butoxycarbonyl) amino] phenyl} boronic acid (8.6 g), triphenylphosphine (150 mg) and PdCl2(PPh3)2 (1.9 g). The mixture was heated to reflux for 4h, the solvent was removed in vacuum, water (150 mL) was added and the mixture was extracted with ethyl acetate (500 mL). The organic phase was dried (sodium sulfate), filtered through Celite and the solvent was removed in vacuum. The residue was titurated with DCM to give the title compound as a white solid. Yield: 7.2 g. 1H-NMR (400MHz, DMSO-d6): delta [ppm]= 1.37 - 1.55 (m, 9H), 5.99 (s, 2H), 7.36 (dd, 1H), 7.48 - 7.55 (m, 2H), 7.55 - 7.62 (m, 2H), 7.69 (dd, 1H), 8.78 (dd, 1H), 9.44 (s, 1H).
	With potassium carbonate; triphenylphosphine;bis-triphenylphosphine-palladium(II) chloride; In propan-1-ol; for 4h;Reflux;	To a stirred solution of Int1.2 (5.82 g) in 1-propanol (400 ml) was added 2M potassium carbonate solution (41 ml), {4-[(tert-butoxycarbonyl) amino] phenyl} boronic acid (8.6 g), triphenylphosphine (150 mg) and PdCl2(PPh3)2 (1.9 g). The mixture was heated to reflux for 4h, the solvent was removed in vacuum, water (150 mL) was added and the mixture was extracted with ethyl acetate (500 mL). The organic phase was dried (sodium sulfate), filtered through Celite and the solvent was removed in vacuum. The residue was triturated with DCM to give the title compound as a white solid. Yield: 7.2 g. 1H-NMR (400MHz, DMSO-d6): delta [ppm]= 1.37 - 1.55 (m, 9H), 5.99 (s, 2H), 7.36 (dd, 1 H), 7.48 - 7.55 (m, 2H), 7.55 - 7.62 (m, 2H), 7.69 (dd, 1 H), 8.78 (dd, 1 H), 9.44 (s, 1 H).

	With potassium carbonate;bis-triphenylphosphine-palladium(II) chloride; triphenylphosphine; In propan-1-ol; water; for 4h;Reflux;	To a stirred solution of Int1.2 (5.82 g) in 1-propanol (400 ml) was added 2M potassium carbonate solution (41 ml), {4-[(tert-butoxycarbonyl) amino] phenyl} boronic acid (8.6 g), triphenylphosphine (150 mg) and PdCl2(PPh3)2 (1.9 g). The mixture was heated to reflux for 4h, the solvent was removed in vacuum, water (150 mL) was added and the mixture was extracted with ethyl acetate (500 mL). The organic phase was dried (sodium sulfate), filtered through Celite and the solvent was removed in vacuum. The residue was titurated with DCM to give the title compound as a white solid. Yield: 7.2 g. 1H-NMR (400MHz, DMSO-d6): delta [ppm]= 1.37 - 1.55 (m, 9H), 5.99 (s, 2H), 7.36 (dd, 1 H), 7.48 - 7.55 (m, 2H), 7.55 - 7.62 (m, 2H), 7.69 (dd, 1 H), 8.78 (dd, 1H), 9.44 (s, 1 H).
	With potassium carbonate;bis-triphenylphosphine-palladium(II) chloride; triphenylphosphine; In propan-1-ol; for 1h;Reflux;	Intermediate Example Int02.01tert-butyl [4-(2-amino[1 ,2,4]triazolo[1 ,5-a]pyridin-6-yl)phenyl]carbamateTo a stirred solution of Int01.02 (12.0 g) in 1 -propanol (350 ml) was added 2M potassium carbonate solution (85 ml), {4-[(tert-butoxycarbonyl) amino] phenyl} boronic acid (14.7 g), triphenylphosphine (739 mg) and PdCl2(PPh3)2 (1.98 g). The mixture was heated to reflux for 1 h, the solvent was removed in vacuum, water (250 mL) was added and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated sodium chloride solution, dried (sodium sulfate), filtered through Celite and the solvent was removed in vacuum. The residue was titurated with DCM to give the title compound as a white solid. Yield: 15.7 g.1H-NMR (400MHz, DMSO-d6): delta [ppm]= 1.37 - 1.55 (m, 9H), 5.99 (s, 2H), 7.36 (dd, 1 H), 7.48 - 7.55 (m, 2H), 7.55 - 7.62 (m, 2H), 7.69 (dd, 1 H), 8.78 (dd, 1 H), 9.44 (s, 1 H).
	With potassium carbonate;bis-triphenylphosphine-palladium(II) chloride; triphenylphosphine; In propan-1-ol; for 4h;Reflux;	Intermediate Example Int3.1tert-butyl [4-(2-amino[1 ,2,4]triazolo[1 ,5-a]pyridin-6-yl)phenyl]carbamateTo a stirred solution of Int 1.2 (5.82 g) in 1 -propanol (400 mL) was added 2M potassium carbonate solution (41 mL), {4-[(£ert-butoxycarbonyl) amino] phenyl} boronic acid (8.6 g), triphenylphosphine (150 mg) and PdCl2(PPh3)2 (1.9 g). The mixture was heated to reflux for 4h, the solvent was removed in vacuum, water (150 mL) was added and the mixture was extracted with ethyl acetate (500 mL). The organic phase was dried (sodium sulfate), filtered through Celite and the solvent was removed in vacuum. The residue was titurated with DCM to give the title compound as a white solid. Yield: 7.2 g. 1H-NMR (400MHz, DMSO-d6): delta [ppm]= 1.37 - 1.55 (m, 9H), 5.99 (s, 2H), 7.36 (dd, 1 H), 7.48 - 7.55 (m, 2H), 7.55 - 7.62 (m, 2H), 7.69 (dd, 1 H), 8.78 (dd, 1 H), 9.44 (s, 1 H).
	With potassium carbonate;[1,4-bis(diphenylphosphino)butane] palladium(ll) dichloride; triphenylphosphine; In propan-1-ol; for 1h;Reflux;	Intermediate Example Int02.01ieri-butyl [4-(2-amino[1 ,2,4]triazolo[1 ,5-a]pyridin-6-yl)phenyl]carbamateTo a stirred solution of Int01.02 (12.0 g) in 1 -propanol (350 mL) was added 2M potassium carbonate solution (85 mL), {4-[(tert-butoxycarbonyl) amino] phenyl} boronic acid (14.7 g), triphenylphosphine (739 mg) and PdCl2(PPh3)2 (1.98 g). The mixture was heated to reflux for 1 h, the solvent was removed in vacuum, water (250 mL) was added and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated sodium chloride solution, dried (sodium sulfate), filtered through Celite and the solvent was removed in vacuum. The residue was titurated with DCM to give the title compound as a white solid. Yield: 15.7 g.1H-NMR (400MHz, DMSO-d6): delta [ppm]= 1.37 - 1.55 (m, 9H), 5.99 (s, 2H), 7.36 (dd, 1 H), 7.48 - 7.55 (m, 2H), 7.55 - 7.62 (m, 2H), 7.69 (dd, 1 H), 8.78 (dd, 1 H), 9.44 (s, 1 H).
7.2 g	With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; triphenylphosphine; In propan-1-ol; for 4h;Reflux;	To a stirred solution of Int01.02 (5.82 g) in 1-propanol (400 mL) was added 2M potassium carbonate solution (41 mL), (4-[(£er£-butoxycarbonyl) amino] phenyl} boronic acid (8.6 g), triphenylphosphine (150 mg) and PdC (PPh3)2 (1.9 g). The mixture was heated to reflux for 4 h, the solvent was removed in vacuum, water (150 mL) was added and the mixture was extracted with ethyl acetate (500 mL). The organic phase was dried (sodium sulfate), filtered through Celite and the solvent was removed in vacuum. The residue was triturated with DCM to give the title compound as a white solid. Yield: 7.2 g. 1H-NMR (400MHz, DMSO-d6): delta [ppm]= 1.37 - 1.55 (m, 9H), 5.99 (s, 2H), 7.36 (dd, 1H), 7.48 - 7.55 (m, 2H), 7.55 - 7.62 (m, 2H), 7.69 (dd, 1H), 8.78 (dd, 1H), 9.44 (s, 1H).
7.2 g	With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; triphenylphosphine; In propan-1-ol; for 4h;Reflux;	To a stirred solution of Int01.02 (5.82 g) in 1 -propanol (400 mL) was added 2M potassium carbonate solution (41 mL), {4-[(tert-butoxycarbonyl) amino] phenyl} boronic acid (8.6 g), triphenylphosphine (150 mg) and PdCl2(PPh3)2 (1.9 g). The mixture was heated to reflux for 4 h, the solvent was removed in vacuum, water (150 mL) was added and the mixture was extracted with ethyl acetate (500 mL). The organic phase was dried (sodium sulfate), filtered through Celite and the solvent was removed in vacuum. The residue was triturated with DCM to give the title compound as a white solid. Yield: 7.2 g. 1H-NMR (400MHz, DMSO-d6): delta [ppm] = 1.37 - 1.55 (m, 9H), 5.99 (s, 2H), 7.36 (dd, 1 H), 7.48 - 7.55 (m, 2H), 7.55 - 7.62 (m, 2H), 7.69 (dd, 1 H), 8.78 (dd, 1 H), 9.44 (s, 1 H).
7.2 g	With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; triphenylphosphine; In propan-1-ol; for 4h;Inert atmosphere; Reflux;	To a stirred solution of Int01 .02 (5.82 g) in 1 -propanol (400 mL) was added 2M potassium carbonate solution (41 mL), {4-[(tert-butoxycarbonyl) amino] phenyl} boronic acid (8.6 g), triphenylphosphine (1 50 mg) and PdCl2(PPh3)2 (1 .9 g). The mixture was heated to reflux for 4 h, the solvent was removed in vacuum, water (150 mL) was added and the mixture was extracted with ethyl acetate (500 mL). The organic phase was dried (sodium sulfate), filtered through Celite and the solvent was removed in vacuum. The residue was triturated with DCM to give the title compound as a white solid. Yield: 7.2 g. 1H-NMR (400MHz, DMSO-de): delta [ppm]= 1 .37 - 1 .55 (m, 9H), 5.99 (s, 2H), 7.36 (dd, 1 H), 7.48 - 7.55 (m, 2H), 7.55 - 7.62 (m, 2H), 7.69 (dd, 1 H), 8.78 (dd, 1 H), 9.44 (s, 1 H).
7.2 g	With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; triphenylphosphine; In propan-1-ol; for 4h;Reflux;	To a stirred solution of Int01.02 (5.82 g) in 1 -propanol (400 mL) was added 2M potassium carbonate solution (41 mL), {4-[(tert-butoxycarbonyl) amino] phenyl} boronic acid (8.6 g), triphenylphosphine (150 mg) and PdCl2(PPh3)2 (1.9 g). The mixture was heated to reflux for 4 h, the solvent was removed in vacuum, water (150 mL) was added and the mixture was extracted with ethyl acetate (500 mL). The organic phase was dried (sodium sulfate), filtered through Celite and the solvent was removed in vacuum. The residue was triturated with DCM to give the title compound as a white solid. Yield: 7.2 g. 1H-NMR (400MHz, DMSO-d6): delta [ppm] = 1.37 - 1.55 (m, 9H), 5.99 (s, 2H), 7.36 (dd, 1 H), 7.48 - 7.55 (m, 2H), 7.55 - 7.62 (m, 2H), 7.69 (dd, 1 H), 8.78 (dd, 1 H), 9.44 (s, 1 H).
7.2 g	With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; triphenylphosphine; In propan-1-ol; for 4h;Reflux;	To a stirred solution of IntOl.02 (5.82 g) in 1-propanol (400 mL) was added 2M potassium carbonate solution (41 mL), f4-[(tert-butoxycarbonyl) amino]phenyl boronic acid (8.6 g), triphenylphosphine (1 50 mg) and PdCI2(PPh3)2 (1 .9g). The mixture was heated to reflux for 4 h, the solvent was removed in vacuum, water (150 mL) was added and the mixture was extracted with ethyl acetate (500 mL). The organic phase was dried (sodium sulfate), filtered through Celite and the solvent was removed in vacuum. The residue was triturated with DCM to give the title compound as a white solid. Yield: 7.2 g.1H-NMR (400MHz, DMSO-d6): 6 [ppm] = 1.37 - 1.55 (m, 9H), 5.99 (5, 2H), 7.36(dd, 1H), 7.48 - 7.55 (m, 2H), 7.55 - 7.62 (m, 2H), 7.69 (dd, 1H), 8.78 (dd, 1H),9.44 (5, 1H).
7.2 g	With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; triphenylphosphine; In propan-1-ol; for 4h;Reflux;	To a stirred solution of Int01.02 (5.82 g) in 1-propanol (400 mL) was added 2M potassium carbonate solution (41 mL), {4-[(tert-butoxycarbonyl)amino]phenyl} boronic acid (8.6 g), triphenylphosphine (150 mg) and PdCl2(PPh3)2 (1.9 g). The mixture was heated to reflux for 4 h, the solvent was removed in vacuum, water (150 mL) was added and the mixture was extracted with ethyl acetate (500 mL). The organic phase was dried (sodium sulfate), filtered through Celite and the solvent was removed in vacuum. The residue was triturated with DCM to give the title compound as a white solid. Yield: 7.2 g. 1H-NMR (400 MHz, DMSO-d6): delta [ppm]=1.37-1.55 (m, 9H), 5.99 (s, 2H), 7.36 (dd, 1H), 7.48-7.55 (m, 2H), 7.55-7.62 (m, 2H), 7.69 (dd, 1H), 8.78 (dd, 1H), 9.44 (s, 1H).

Reference： [1]Patent: WO2011/64328,2011,A1 .Location in patent: Page/Page column 65-66
[2]Patent: WO2011/63908,2011,A1 .Location in patent: Page/Page column 55
[3]Patent: EP2343295,2011,A1 .Location in patent: Page/Page column 25
[4]Patent: EP2343297,2011,A1 .Location in patent: Page/Page column 26
[5]Patent: WO2011/157688,2011,A1 .Location in patent: Page/Page column 93
[6]Patent: WO2012/143329,2012,A1 .Location in patent: Page/Page column 74
[7]Patent: WO2012/160029,2012,A1 .Location in patent: Page/Page column 70
[8]Patent: WO2013/87579,2013,A1 .Location in patent: Page/Page column 94
[9]Patent: WO2014/9219,2014,A1 .Location in patent: Page/Page column 68; 69
[10]Patent: WO2014/20041,2014,A1 .Location in patent: Page/Page column 124-125
[11]Patent: WO2014/195276,2014,A1 .Location in patent: Page/Page column 97
[12]Patent: WO2014/198647,2014,A2 .Location in patent: Page/Page column 70; 71
[13]Patent: US2015/148542,2015,A1 .Location in patent: Paragraph 0329-0331

36
[ 1124382-65-5 ]
[ 380430-49-9 ]
[ 1309474-11-0 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;bis-triphenylphosphine-palladium(II) chloride; triphenylphosphine; In propan-1-ol; for 4.5h;Reflux;	Intermediate Example Int2.1tert-butyl [4-(2-amino-5-methyl[1 ,2,4]triazolo[1 ,5-a]pyridin-6- yl)phenyl]carbamateTo a stirred solution of Int1.2 (1.0 g) in 1 -propanol (70 ml) was added 2M potassium carbonate solution (6.6 ml), {4-[(tert-butoxycarbonyl) amino] phenyl} boronic acid (1.39 g), triphenylphosphine (24 mg) and PdC iPPhs (309 g). The mixture was heated to reflux for 4.5 h. Approx. 50 mL of the solvent were removed in vacuum and 300 mL of a mixture of DCM and methanol (100:1 ) were added. The mixture was filtered and the solution was washed with water and with saturated sodium chloride solution. The organic phase was dried (sodium sulfate), and the solvent was removed in vacuum. Silica gel chromatography gave 980 mg of the title compound.1H-NMR (400MHz, DMSO-d6): delta [ppm]= 1.49 (s, 9H), 2.54 (s, 3H), 6.04 (s, 2H), 7.23 - 7.37 (m, 4H), 7.55 (d, 2H), 9.48 (s, 1H).

Reference： [1]Patent: WO2011/63907,2011,A1 .Location in patent: Page/Page column 54
[2]Patent: EP2343294,2011,A1 .Location in patent: Page/Page column 24-25

37
[ 890850-18-7 ]
[ 380430-49-9 ]
[ 1158651-00-3 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); Aliquat 336; In water; toluene; at 90℃; for 3h;Inert atmosphere; septum-sealed flask;	Compound 1 (4.0 g, 6.3 mmol) was dissolved in 60 mL toluene in a 2 neck 200 mL septum-sealed round bottom. 4-[(tert-Butoxycarbonyl)amino]benzeneboronic acid (3.72 g, 15.7 mmol), Aliquat 336 (0.5 g) and sodium carbonate (3.33 g, 31.4 mmol) were added. The mixture was sparged with nitrogen and the reaction flask was fitted with a reflux condenser and nitrogen inlet-outlet. In a nitrogen purged glovebox, tetrakistriphenylphosphine (363 mg, 5.00 mol %) and anhydrous toluene (10 mL) were combined in a round bottom flask. The flask was sealed with a septum and removed from the glovebox. The catalyst suspension was added to the reaction mixture via a cannula. Water (30 mL) was added to the reaction vessel via syringe. The nitrogen sparge was removed and replaced with a nitrogen blanket. The reaction mixture was heated at 90 C. for 3 h. The reaction was allowed to cool to room temperature, transferred to a separatory funnel and diluted with ethyl acetate. The aqueous layer was removed and the organic layer was washed with water, then with brine and dried over MgSO4. The crude product was filtered through a pad of silica gel, rinsing with ethyl acetate. The solvent was removed and the product was dried under high vacuum. After purification by flash column chromatography (3:2 hexanes:methylene chloride), 2.2 g of a light orange foamy solid was obtained. Purity (HPLC): 98.5%, pure 4,4' isomer. NMR analysis confirmed the structure of Intermediate Compound 2.

Reference： [1]Patent: US2012/65432,2012,A1 .Location in patent: Page/Page column 22

38
[ 380430-49-9 ]
[ 1246203-33-7 ]

Yield	Reaction Conditions	Operation in experiment
71%	With potassium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; water; for 1h;Reflux; Inert atmosphere;	A mixture of l-[4-chloro-6-(4-morpholinyl)-l,3,5-triazin-2-yl]-2-(difiuoromethyl)-4-methoxy-lH-benzimidazole (WO 2009/120094) (100 mg, 0.252 mmol), 4-[(tert-butoxycarbonyl)amino]phenylboronic acid (90 mg, 0.380 mmol), PdCl2(dppf) (10.3 mg, 0.0126 mmol), and aq. K2C03 (2M, 2 mL) in 1,4-dioxane (10 mL) was refluxed under nitrogen for 1 hr. The mixture was cooled to room temperature and diluted with H20. The aqueous phase was extracted with CH2C12 (3 x). The combined organic extracts were dried (Na2S04) and the solvent was removed under vacuum. Chromatography on alumina, eluting with CH2C12, followed by recrystallization from CH2Cl2/MeOH/hexanes gave tert-butyl 4-[4- [2-(difluoromethyl)-4-methoxy- 1 H-benzimidazol- 1 -yl] -6-(4-morpholinyl)- 1 ,3 ,5 -triazin-2- yl]phenylcarbamate (99 mg, 71%): mp (CH2Cl2/MeOH/hexanes) 188-190 C; 1H NMR (CDCls) delta 8.41 (d, J= 8.8 Hz, 2H), 8.08 (dd, J= 8.4, 0.6 Hz, 1H), 7.62 (t, JHF = 53.4 Hz, 1H), 7.52 (d, J= 8.8 Hz, 2H), 7.41 (t, J= 8.2 Hz, 1H), 6.86 (d, J= 7.7 Hz, 1H), 6.69 (s, 1H), 4.12 (m, 2H), 4.07 (s, 3H), 3.99 (m, 2H), 3.85 (m, 4H), 1.55 (s, 9H); Anal. Calcd. forC27H29F2N704: C, 58.6; H, 5.3; N, 17.2; Found: C, 58.5; H, 5.0; N, 17.2%.

Reference： [1]Patent: WO2012/44641,2012,A1 .Location in patent: Page/Page column 46; 82-84

39
C₂₃H₃₀INO₄S [ No CAS ]
[ 380430-49-9 ]
[ 1383385-81-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In water; N,N-dimethyl-formamide; at 92℃; for 4h;Inert atmosphere;	[528] A mixture of 122A, [4-({ [(l,l-dimethylethyl)oxy]-carbonyl}amino)phenyl]boronic acid (0.2 mmol), Pd(dppf)Cl2 (0.01 mmol), and Na2C03 (0.3 mmol) in DMF (2 mL) and H20 (0.5 mL) under N2 is stirred at 92 C for 4 hr. The reaction is diluted with EtOAc (50 mL), washed with water (2x10 mL) and brine (10 mL), dried over anhydrous Na2S04, and concentrated under reduced pressure. The residue is purified by flash chromatography (silica gel), eluting with 0-5% MeOH in CH2C12 to give 122B.

Reference： [1]Patent: WO2012/83105,2012,A1 .Location in patent: Page/Page column 119

40
[ 1383384-96-0 ]
[ 380430-49-9 ]
[ 1383384-98-2 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In water; N,N-dimethyl-formamide; at 92℃; for 4h;Inert atmosphere;	[227] Example 4 - 5-(4-Amino-phenyl)-3-ri-methyl-5-(4-methyl-cvclohexyl)-l,2,3,6-tetrahydro- pyridin-4-nuPi -thiophene-2-carboxylic acid; [228] DMF ( 10 mL) and H20 (2 mL) were added to a mixture of [4-( { [( 1 , 1 - dimethylethyl)oxy] - carbonyl}amino)phenyl]boronic acid (0.33 g, 1.4 mmol), 002G (0.42 g, 0.91 mmol), Pd(dppf)Cl2 (0.033 g, 0.0455 mmol), and sodium carbonate (0. 3 g, 2.8 mmol) under N2, and the mixture was stirred at 92 C for 4 hr. The reaction was cooled to RT, and to it was added ice- water and EtOAc. The organic layer was washed with water (3x) and the combined aqueous layers were back-extracted with EtOAc (2x). The combined organic layers were washed with brine, dried over anhydrous Na2S04, and concentrated under reduced pressure. The product was purified by flash chromatography (silica gel), eluting with 0-5% MeOH in CH2C12 to give 004A as an oil. MS calcd: (M+H)+ = 525. MS found: (M+H)+ = 525.

Reference： [1]Patent: WO2012/83105,2012,A1 .Location in patent: Page/Page column 60-61

41
[ 1383385-03-2 ]
[ 380430-49-9 ]
[ 1383385-06-5 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In water; N,N-dimethyl-formamide; at 92℃; for 4h;Inert atmosphere;	[266] Example 18 - 5-(4-Acetylamino-phenyl')-3-ri-ethyl-5-(4-methyl-cyclohexyl')-l,2,3,6- tetrahydro-pyridin-4-yll -thiophene-2-carboxylic acid; [267] DMF ( 10 mL) and H20 (2 mL) were added to a mixture of [4-( { [( 1 , 1 - dimethylethyl)oxy]carbonyl}amino)phenyl]boronic acid (0.33 g, 1.4 mmol), 014C (0.43 g, 0.91 mmol), Pd(dppf)Cl2 (0.033 g, 0.0455 mmol) and sodium carbonate (0. 3 g, 2.8 mmol) under N2, and stirred at 92 C for 4 hr. The reaction was cooled to RT, and to it was added ice- water and EtOAc. The organic layer was washed with water (3x) and the combined aqueous layers were back-extracted with EtOAc (2x). The combined organic layers were washed with brine, dried over anhydrous Na2S04, and concentrated under reduced pressure. The product was purified by flash chromatography (silica gel), eluting with 0-5% MeOH in CH2C12 to give 018A. MS calcd: (M+H)+ = 539. MS found: (M+H)+ = 539.

Reference： [1]Patent: WO2012/83105,2012,A1 .Location in patent: Page/Page column 68

42
[ 1402465-77-3 ]
[ 380430-49-9 ]
[ 1402465-80-8 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; water; at 90℃; for 16h;Inert atmosphere;	Intermediate 8(R)- l-(2-Chlorophenyl)ethyl (4-(4-(tert-butoxycarbonylamino)phenyl)- 1-methyl- lH-pyrazol-5- yPcarbamate[0202] A mixture of (R)-l-(2-chlorophenyl)ethyl-4-bromo-l-methyl-lH-pyrazol-5- ylcarbamate (INT-3a, 716 mg, 2.0 mmol), 4-(tert-butoxycarbonylamino)phenylboronic acid (711 mg, 3.0mmol), PdC^dppf'DCM (245 mg, 0.3 mmol), and sodium bicarbonate (340 mg, 4.0mmol) was degassed and flushed with argon. Dioxane (12 mL) and water (4 mL) were added and the mixture was heated at 90 C with stirring for 16 h. The cooled mixture was filtered through celite, and the filter cake was rinsed with ethyl acetate. The combined filtrate was washed with water and brine, dried over sodium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography to give the title compound (M+l 471.2).

Reference： [1]Patent: WO2012/138648,2012,A1 .Location in patent: Page/Page column 79-80

43
[ 1059065-44-9 ]
[ 380430-49-9 ]
[ 1059065-48-3 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 80℃; for 3h;	Example 5. Representative General Procedure for Synthesis of C5-Arylurea Compounds from (E)S, 7- Dichloro-benzodiazepin-2(3H)-one Intermediates.Method A:Part I: Installation of C-5 Aryl Substituent.NHBoc(Z)-tert-Butyl-4-(7-chloro-l-(4-methoxybenzyl)-2-oxo-2,3-dihydro-lH- benzo[e][l,4]diazepin-5-yl)phenylcarbamate. Imidoyl chloride (5.5 g, 15.7 mmol) was treated with (4-tert-butoxycarbonylaminophenyl)boronic acid (3.72 g, 18.84 mmol), Pd(PPh3^ (0.362 g, <n="94"/>0.314 mmol), 2N aqueous Na2CO3 (23.5 mL), and DME (2.5 mL), degassed with nitrogen and heated at 80 0C for 3h. The reaction mixture was cooled, diluted with EtOAc (200 mL) and poured into water (200 mL). The layers were separated and the aqueous was extracted with EtOAc (100 mL). The combined extracts were washed with brine (200 mL), dried over MgStheta4, and evaporated to dryness. The crude material was purified by flash column chromatography (eluted with 20 % EtOAc in Hexane) to give (Z)-tert-butyl 4-(7-chloro-l-(4-methoxybenzyl)-2- oxo-2,3-dihydro-lH-benzo[e][l,4]diazepin-5-yl)phenylcarbamate (3.4 g, 42.8 %) as a pale solid. 1H NMR (400 MHz, CDCl3) D 1.55 (s, 9H), 3.73 (s, 3H), 3.83 (d, IH), 4.63 (d, IH), 4.86 (d, IH), 5.59 (d, IH), 6.63 (d, 2H), 6.66 (d, 2H), 6.93 (d, 2H), 7.17 (s, IH), 7.28 (s, 2H), 7.32-7.41 (m, 6H). MS m/z 507.3 [M + 1]

Reference： [1]Patent: WO2008/112553,2008,A1 .Location in patent: Page/Page column 92-93

44
[ 313339-92-3 ]
[ 380430-49-9 ]
[ 1426214-81-4 ]

Yield	Reaction Conditions	Operation in experiment
61%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 1h;	1-(3,5-Dichloro-pyrazin-2-yl)-ethanone (2.2 g), prepared as described in example 10, and (4-tert-butoxycarbonyl-aminophenyl)boronic acid (2.7 g), was added to a reaction vessel containing a magnetic stirring bar together with 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) dichloride (674 mg) and cesium carbonate (11.2 g), followed by 100 ml dioxane and 10 ml water, and the mixture heated to 100C under stirring. After 1 h the reaction mixture was cooled to RT and quenched with a saturated aqueous sodium bicarbonate solution (50 ml) and extracted with EtOAc (3 x 100 ml). The combined organic phases were dried over sodium sulfate, filtered and evaporated to afford the crude product as a dark brown oil. Purification by flash chromatography on silica gel using a mixture of EtOAc and heptane as the eluent afforded [4-(5-acetyl-6-chloro-pyrazin-2-yl)-phenyl]-carbamic acid tert-butyl ester as a colorless solid after evaporation of the solvents under reduced pressure. Yield: 2.44g (61 %) mg.

Reference： [1]Patent: EP2570415,2013,A1 .Location in patent: Paragraph 0135

45
[ 1196-90-3 ]
[ 380430-49-9 ]
[ 864076-02-8 ]

Yield	Reaction Conditions	Operation in experiment
97%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; at 100℃; for 0.2h;Inert atmosphere; Microwave irradiation;	A catalytic amount of tetrakis(triphenylphosphine)palladium, Pd(PPh3)4 (0.477g, 0.413, 0.06 eq) was added to a solution of 4 (1.5 g, 6.88 mmol, 1 eq) and (4-((tert- butoxycarbonyl)amino)phenyl)boronic acid (1.57 g, 6.88 mmol, 1.20 eq) in a 9:3: 1 combination (13.5 ml) of EtOH, toluene and water in the presence of K2C03 (2.856 g, 3 eq.) in a 10-20 mL microwave vial containing a magnetic stirrer. The reaction vessel was flushed with nitrogen during each addition. The reaction mixture was sealed in an inert N2 atmosphere and heated with microwave radiation in an EMRYS Optimizer Microwave Station (Personal Chemistry) at 100C for 12 minutes. After LCMS and TLC analysis revealed completion of the reaction, the cooled reaction mixture was diluted with water (50 mL), extracted with EtOAc (3 x 40 mL), the filtrates combined, dried over MgS04 and concentrated under vacuum. The resulting oil was subjected to flash chromatography (n-hexane/EtOAc 9: 1) to give 5 (Yield - 2.2 g, 97%). IR (FTIR, vmax /cm" ): 3353, 2975, 1696, 1521 , 1441 , 1366, 1264, 1235, 1209, 1058, 822, 799, 657; H- NMR (400 MHz, CDCI3): delta 7.40 (d, 2H, J = 8.8 Hz), 7.33 (d, 2 H, J = 8.8 Hz), 7.16 (d, 1 H, J = 2.0 Hz,), 7.02 (d, 1 H, J = 2.0), 6.45 (br s, 1 H), 3.95 (s, 3H), 3.83 (s, 3H), 1.52 (s, 9H); 3C-NMR (100 MHz, CDCI3): delta 161.7, 152.8, 136.5, 129.5, 125.9, 125.6, 123.7, 123.0, 119.0, 1 14.6, 80.5, 51.1 , 36.9, 28.4; EIMS m/z (+EI) calc. for C18H22N204 (M)+ 330.38 found 330.46 (M+H)+
97%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; at 100℃; for 0.2h;Inert atmosphere; Microwave irradiation;	A catalytic amount of tetrakis(triphenylphosphine)palladium, Pd(PPh3)4 (0.477g, 0.413, 0.06 eq) was added to a solution of 4 (1.5 g, 6.88 mmol, 1 eq) and (4-((tert- butoxycarbonyl)amino)phenyl)boronic acid (1.57 g, 6.88 mmol, 1.20 eq) in a 9:3: 1 combination (13.5 ml) of EtOH, toluene and water in the presence of K2C03 (2.856 g, 3 eq.) in a 10-20 mL microwave vial containing a magnetic stirrer. The reaction vessel was flushed with nitrogen during each addition. The reaction mixture was sealed in an inert N2 atmosphere and heated with microwave radiation in an EMRYS Optimizer Microwave Station (Personal Chemistry) at 100C for 12 minutes. After LCMS and TLC analysis revealed completion of the reaction, the cooled reaction mixture was diluted with water (50 mL), extracted with EtOAc (3 x 40 mL), the filtrates combined, dried over MgS04 and concentrated under vacuum. The resulting oil was subjected to flash chromatography (n-hexane/EtOAc 9: 1) to give 5 (Yield - 2.2 g, 97%). IR (FTIR, vmax /cm" ): 3353, 2975, 1696, 1521 , 1441 , 1366, 1264, 1235, 1209, 1058, 822, 799, 657; H- NMR (400 MHz, CDCI3): delta 7.40 (d, 2H, J = 8.8 Hz), 7.33 (d, 2 H, J = 8.8 Hz), 7.16 (d, 1 H, J = 2.0 Hz,), 7.02 (d, 1 H, J = 2.0), 6.45 (br s, 1 H), 3.95 (s, 3H), 3.83 (s, 3H), 1.52 (s, 9H); 3C-NMR (100 MHz, CDCI3): delta 161.7, 152.8, 136.5, 129.5, 125.9, 125.6, 123.7, 123.0, 119.0, 1 14.6, 80.5, 51.1 , 36.9, 28.4; EIMS m/z (+EI) calc. for C18H22N204 (M)+ 330.38 found 330.46 (M+H)+
57%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; at 80℃; for 3.5h;Inert atmosphere;	Boronic acid 21 (652 mg, 2.75 mmol) and compound 22 (500 mg, 2.293 mmol) were dissolved in EtOH (5.29 mL), toluene (1.76 mL) and water (588 pL). K2C03 (951 mg, 6.88 mmol) and Pd(PPh3)4 (159 mg, 0.138 mmol) were added and the solution was purged and degassed with Ar. The reaction was heated at 80 C for 3.5 h. The reaction mixture was cooled to rt and was diluted with EtOAc. The organic layer was washed with water, brine, dried over Na2S04, filtered and concentrated. The crude product was purified by silica gel chromatography (0% to 20% to 50% EtOAc/hexanes) to obtain compound 23 as a yellow solid (432 mg, 1.308 mmol, 57% yield). 1H NMR (400 MHz, CDCl3): d 1.52 (s, 9H), 3.84 (s, 3H), 3.95 (s, 3H), 6.44 (s, 1H), 7.03 (d, 7 = 2.1 Hz, 1H), 7.16 (d, 7 = 2.0 Hz, 1H), 7.32 - 7.34 (m, 2H), 7.37 - 7.44 (m, 2H).

42%

With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In water; acetonitrile; at 100℃; for 0.1h;Inert atmosphere; Microwave irradiation;

Example 52: - Synthesis of methyl 4-(4-((tert-butoxycarbonyl)amino)- ph e n yl)-l-methyl-lH -pyrrole -2 -carboxylate (37) (0780) (0781) Methyl 4-bromo-i-methyl-iH-pyrrole-2-carboxylate (1 g, 4.60 mmols), (4-((tert- butoxycarbonyl)amino)phenyl)boronic acid (1.2 g, 1.1 equiv.), K2C03 (1.7 g, 3 equiv.) were solubilized in a mixture of ACN (40 mL) and H20 (36 mL) in a microwave vial. The reaction mixture was left under magnetic stirrer in N2 atmosphere for 5 minutes. At that point Tetrakis Pd (0.280 g, 0.05 equiv.) was added. The reaction mixture was then heated at MW radiation at 1000 C for 6 minutes. LC-MS showed the formation of the product. The reaction mixture was filtered under vacuum through a path of celite previously washed with AcOEt. The resulting solution, brown in colour, was then evaporated using a rotary evaporator. The obtained residue was purified by column chromatography (mobile phase: DCM/AcOEt, 80/20, v/v) giving pure 37 (0.635 g, 42%) as an amber oil. NMR (400 MHz, CHLOROFORM-d) delta: 7.47 - 7.52 (m, lH), 7.41 - 7.44 (m, 2H), 7.32 - 7.38 (m, 2H), 7.17 (d, J = 2.01 Hz, lH), 7.04 (d, J = 2.27 Hz, lH), 3.96 (s, 3H), 3-85 (s, 3H), 1.53 (s, 9H). C NMR (101 MHz, CHLOROFORM-d) delta: i6i.9, 153-1, 136.8, 135-7, 129-4, 127-2, 126.2, 123.5, H9-2, H4-7, 80.5, 5i-i, 37-2, 28.4. m/z (+EI) calc. for Cl8H22N204 (M)+ 330.1 found 331-0 ([M]+H)+.

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 2911 - 2935
[2]Patent: WO2013/164592,2013,A1 .Location in patent: Page/Page column 50; 51
[3]Patent: WO2013/164593,2013,A1 .Location in patent: Page/Page column 42; 43
[4]Patent: WO2019/133652,2019,A1 .Location in patent: Page/Page column 138; 146
[5]Patent: WO2017/98257,2017,A1 .Location in patent: Page/Page column 91

46
[ 136866-39-2 ]
[ 380430-49-9 ]
[ 1426214-81-4 ]

Yield	Reaction Conditions	Operation in experiment
61%	With palladium bis[bis(diphenylphosphino)ferrocene] dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 1h;	1-(3,5-Dichloro-pyrazin-2-yl)-ethanone (2.2 g), prepared as described in example 10, and (4-tert-butoxycarbonyl-aminophenyl)boronic acid (2.7 g), was added to a reaction vessel containing a magnetic stirring bar together with 1,1'-bis(diphenylphosphino)ferrocene-palladium(ll) dichloride (674 mg) and cesium carbonate (11 .2 g), followed by 100 ml dioxane and 10 ml water, and the mixture heated to 100 C under stirring. After 1 h the reaction mixture was cooled to RT and quenched with a saturated aqueous sodium bicarbonate solution (50 ml) and extracted with EtOAc (3 x 100 ml). The combined organic phases were dried over sodium sulfate, filtered and evaporated to afford the crude product as a dark brown oil. Purification by flash chromatography on silica gel using a mixture of EtOAc and heptane as the eluent afforded [4-(5-acetyl-6-chloro-pyrazin-2-yl)-phenyl]-carbamic acid tert-butyl ester as a colorless solid after evaporation of the solvents under reduced pressure. Yield: 2.44 g (61 %).
61%	With palladium bis[bis(diphenylphosphino)ferrocene] dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 1h;	1-(3,5-Dichloro-pyrazin-2-yl)-ethanone (2.2 g), prepared as described in example 10, and (4-tert-butoxycarbonyl-aminophenyl)boronic acid (2.7 g), was added to a reaction vessel containing a magnetic stirring bar together with 1,1'- bis(diphenylphosphino)ferrocene-palladium(ll) dichloride (674 mg) and cesium carbonate (11 .2 g), followed by 100 ml dioxane and 10 ml water, and the mixture heated to 100C under stirring. After 1 h the reaction mixture was cooled to RT and quenched with a saturated aqueous sodium bicarbonate solution (50 ml) and extracted with EtOAc (3 x 100 ml). The combined organic phases were dried over sodium sulfate, filtered and evaporated to afford the crude product as a dark brown oil. Purification by flash chromatography on silica gel using a mixture of EtOAc and heptane as the eluent afforded [4-(5-acetyl-6-chloro-pyrazin-2-yl)-phenyl]-carbamic acid tert-butyl ester as a colorless solid after evaporation of the solvents under reduced pressure. Yield: 2.44g (61 %) mg
61%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 1h;	(i) [4-(5-Acetyl-6-chloro-pyrazin-2-yl)-phenyl]-carbamic acid tert-butyl ester 1-(3,5-Dichloro-pyrazin-2-yl)-ethanone (2.2 g), prepared as described in example 10, and (4-tert-butoxycarbonyl-aminophenyl)boronic acid (2.7 g), was added to a reaction vessel containing a magnetic stirring bar together with 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) dichloride (674 mg) and cesium carbonate (11.2 g), followed by 100 ml dioxane and 10 ml water, and the mixture heated to 100 C. under stirring. After 1 h the reaction mixture was cooled to RT and quenched with a saturated aqueous sodium bicarbonate solution (50 ml) and extracted with EtOAc (3*100 ml). The combined organic phases were dried over sodium sulfate, filtered and evaporated to afford the crude product as a dark brown oil. Purification by flash chromatography on silica gel using a mixture of EtOAc and heptane as the eluent afforded [4-(5-acetyl-6-chloro-pyrazin-2-yl)-phenyl]-carbamic acid tert-butyl ester as a colorless solid after evaporation of the solvents under reduced pressure. Yield: 2.44 g (61%) mg.

61%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 1h;	According to an embodiment 10 of the preparation described in 1-(3,5-dichloro-pyrazine-2-yl)-ethanone (2.2g) and (4-tert-butoxy carbonyl-aminophenyl) boric acid (2.7g) adding to the containing magnetic stirring rod and 1, the 1,1'-bis(diphenylphosphino)ferrocene palladium dichloride (674 mg) and cesium carbonate (11.2g) in the reaction container, subsequently joined 100 ml dioxane and 10 ml of water, the mixture is heated under stirring to 100 C. 1h reaction mixture after cooling to the room temperature and with the saturated aqueous solution of sodium bicarbonate (50 ml) for quenching and EtOAc (3×100 ml) extraction. The combined organic phase is dried with sodium sulfate, filtered and evaporation to obtain dark brown oily crude product. Fast by silica gel chromatography using EtOAc and heptane mixture of purification as an eluent, obtained after evaporation of the solvent under reduced pressure to the colorless solid [4 - (5-acetyl-6-chloro-pyrazin-2-yl)-phenyl]-amino- formic acid uncle contact. Yield: 2.44g (61%).
61%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; water; at 100℃; for 1h;	(3,5-dichloro-pyrrazin-2-yl)-ethanone (2.2 g) prepared as described in Example 10 (2.2 g) and (4-tert-butoxycarbonyl-aminophenyl) boronic acid(2.7 g) was added to a solution of 1,1'-bis (diphenylphosphino) ferrocene-paradium (II) dicloride (674 mg) and sodium carbonate (11.2 g), followed by addition of 100 ml of dioxane and 10 ml of water, and the mixture was heated to 100 C. under stirring.After 1 h the reaction mixture was cooled to room temperature and quenched with saturated aqueous sodium bicarbonate solution (50 ml) and extracted with EtOAc (3 × 100 ml). The combined organic phases were dried over sodium sulfate, filtered and evaporated to give the crude product as a thick brown oil. After purification by flash chromatography on silica gel using a mixture of EtOAc and heptane as eluent and evaporation of the solvent under reduced pressure, [4- (5-acetyl-6-chloro-pyrazin-2 - yl) -phenyl] -carbamic acid tert-butyl ester. Yield: 2.44 g (61%)

Reference： [1]Patent: WO2013/41502,2013,A1 .Location in patent: Page/Page column 96; 97
[2]Patent: WO2013/41119,2013,A1 .Location in patent: Page/Page column 95; 96
[3]Patent: US2013/72493,2013,A1 .Location in patent: Paragraph 0339
[4]ACS Medicinal Chemistry Letters,2015,vol. 6,p. 73 - 78
[5]Patent: CN103012407,2016,B .Location in patent: Paragraph 0363; 0365; 0366
[6]Patent: JP5827849,2015,B2 .Location in patent: Paragraph 0141

47
[ 2120-82-3 ]
[ 380430-49-9 ]
[ 1446247-77-3 ]

Yield	Reaction Conditions	Operation in experiment
85%	With potassium fluoride; 18-crown-6 ether; palladium diacetate; In toluene; for 6h;Reflux;	A mixture of 3,5-dichloroisothiazole-4-carbonitrile (5.37 g, 30 mmol), 4- (tertbutoxycarbonylamino)phenylboronic acid (14.22 g, 60 mmol), potassium fluoride (6.1 1 g, 105 mmol), 18-crown-6 (3.96 g, 15 mmol), and palladium acetate (337 mg, 1.5 mmol) in toluene (250 ml) was heated at reflux for 6 hours. The reaction was cooled to RT and the mixture was diluted with water and EtOAc. Layers were separated and the aqueous layer was extracted with EtOAcx3. The combined organics was washed with brine and dried with MgS04, filtered, and concentrated. The crude product was purified by flash silica gel column eluted with 5-15% EtOAc in hexanes to obtain the above compound as a white crystalline solid (8.55g, 85%). NMR and MS spectra are consistent with the structure. HPLC purity 97.6%.

Reference： [1]Patent: WO2013/101954,2013,A1 .Location in patent: Page/Page column 48; 49; 69

48
[ 1374108-96-9 ]
[ 380430-49-9 ]
[ 1374109-10-0 ]

Yield	Reaction Conditions	Operation in experiment
90%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,2-dimethoxyethane; water; at 85℃; for 24h;Inert atmosphere;	Synthesis of 131 A mixture of 115 (625 mg, 1.69 mmol), 130 (593 mg, 1.86 mmol), potassium carbonate (467 mg, 3.40 mmol), tetrakistriphenylphosphine palladium (195 mg, 0.169 mmol) and 1,2-dimethoxyethane (4.5 ml)-water (0.5 ml) was stirred under an argon atmosphere at 85C for 16 hours, and tetrakistriphenylphosphine palladium (98 mg, 0.085 mmol) was added, followed by further stirring at the same temperature for 8 hours. The reaction solution was allowed to return to room temperature and chloroform was added, and then insolubles were removed by filtration and the solution was washed with chloroform. The chloroform layers were combined and dried, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel flash column chromatography (eluting solvent: ethyl acetate/n-hexane = 1/19, 1/9, 1/6) to obtain 131 (799 mg, 90%) as a pale brown solid. APCI-MS m/z 527[M+H]+

Reference： [1]Patent: EP2634177,2013,A1 .Location in patent: Paragraph 0336; 0337

49
[ 16308-68-2 ]
[ 459-64-3 ]
[ 380430-49-9 ]
tert-butyl (4-(1-(4-methoxyphenyl)-3-((phenoxycarbonyl)oxy)propyl)phenyl)carbamate [ No CAS ]

Reference： [1]Organic Letters,2013,vol. 15,p. 5008 - 5011

50
[ 76-09-5 ]
[ 380430-49-9 ]
[ 330793-01-6 ]

Yield	Reaction Conditions	Operation in experiment
99%	With 1H-imidazole; iron(III) chloride; In water; acetonitrile; at 20℃; for 0.5h;Inert atmosphere;	General procedure: To a solution of aryl boronic acid (1 mmol) in MeCN (4 mL) was added, sequentially, asolution of FeCl3 (8 mg, 0.05 mmol, 5 mol%) in H2O (1 mL), imidazole (204 mg, 3 mmol)and pinacol (118 mg, 1 mmol). The resulting cloudy orange mixture was stirred at roomtemperature for 30 min. The reaction was then diluted with H2O (5 mL) and extracted withEt2O (3 x 8 mL). The combined organic extracts were dried (Na2SO4) and concentrated invacuo. The resulting oil was then purified by a filtration through a silica gel plug (eluting withEt2O), affording the title compound.

Reference： [1]Synlett,2014,vol. 25,p. 551 - 555
[2]Angewandte Chemie - International Edition,2019,vol. 58,p. 6554 - 6558
Angew. Chem.,2019,vol. 131,p. 6626 - 6630,5

51
[ 2257-69-4 ]
[ 380430-49-9 ]
tert-butyl (4-(4-oxo-3,4-dihydrophthalazin-1-yl)phenyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 150℃; for 0.583333h;Inert atmosphere; Sealed tube; Microwave irradiation;	Intermediate 3A tert-butyl (4-(4-oxo-3,4-dihydrophthalazin-1-yl)phenyl)carbamate [0478] [0479] To 4-chlorophthalazin-1(2H)-one (118 mg, 0.653 mmol), <strong>[380430-49-9](4-((tert-butoxycarbonyl)amino)phenyl)boronic acid</strong> (170 mg, 0.719 mmol) and potassium phosphate (347 mg, 1.634 mmol), were added dioxane (9 mL) and water (1 mL). The mixture was degassed (evacuated and flushed with Ar (5×)). Pd(PPh3)4 (37.8 mg, 0.033 mmol) was added, then the mixture was degassed (2×). The reaction vial was sealed and heated in a microwave reactor at 150 C. for 35 min. The reaction mixture was concentrated and purified via flash chromatography to afford 150 mg (68%) of Intermediate 3A. [0480] MS (ESI) m/z: 338.1 (M+H)+.

Reference： [1]Patent: US2014/206686,2014,A1 .Location in patent: Paragraph 0478-0480

52
[ 1417885-96-1 ]
[ 380430-49-9 ]
[ 1265176-46-2 ]

Yield	Reaction Conditions	Operation in experiment
79%	With bis-triphenylphosphine-palladium(II) chloride; potassium fluoride; In water; acetonitrile; at 115℃; for 0.333333h;Sealed tube; Microwave irradiation;	To a 5-mL microwave vial was added <strong>[380430-49-9](4-((tert-butoxycarbonyl)amino)phenyl)boronic acid</strong> (139 mg, 0.584 mmol)), 3-bromo-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole (150 mg, 0.487 mmol)], KF (73.6 mg, 1.266 mmol)), and PdCl2(PPh3)2 (34.2 mg, 0.049 mmol). Subsequently, MeCN (2.092 mL))/water (2.092 mL) was added. The reaction vial was then sealed and the reaction was heated at 115 C. for 20 min in a Biotage Initiator microwave reactor with external IR-sensor temperature monitoring from the side of the vessel. The reaction mixture was cooled to RT, diluted with CH2Cl2 and water. The organics were collected using a phase separator and concentrated. The crude product was purified by reverse phase flash chromatography (silica, hexanes/EtOAc) to yield the title compound as an off white solid (165 mg, 79%).
79%	With bis-triphenylphosphine-palladium(II) chloride; potassium fluoride; In water; acetonitrile; at 115℃; for 0.333333h;Sealed tube; Microwave irradiation;	To a 5-mL microwave vial was added <strong>[380430-49-9](4-((tert-butoxycarbonyl)amino)phenyl)boronic acid</strong> (139 mg, 0.584 mmol)), 3-bromo-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole (150 mg, 0.487 mmol)], KF (73.6 mg, 1.266 mmol)), and PdCl2(PPh3)2 (34.2 mg, 0.049 mmol). Subsequently, MeCN (2.092 mL))/water (2.092 mL) was added. The reaction vial was then sealed and the reaction was heated at 115 C. for 20 min in a Biotage Initiator microwave reactor with external IR-sensor temperature monitoring from the side of the vessel. The reaction mixture was cooled to RT, diluted with CH2Cl2 and water. The organics were collected using a phase separator and concentrated. The crude product was purified by flash column chromatography using hexanes/EtOAc) to the title compound as an off white solid (165 mg, 79%).
79%	With bis-triphenylphosphine-palladium(II) chloride; potassium fluoride; In water; acetonitrile; at 115℃; for 0.333333h;Microwave irradiation; Sealed tube;	To a 5-mL microwave vial was added <strong>[380430-49-9](4-((tert-butoxycarbonyl)amino)phenyl)boronic acid</strong> (139 mg, 0.584 mmol)),3-bromo-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole (150 mg, 0.487 mmol)], KF (73.6 mg, 1.266 mmol)), and PdCl2(PPh3)2 (34.2 mg, 0.049 mmol). Subsequently, MeCN (2.092 mL)/water (2.092 mL) was added. The reaction vial was then sealed and the reaction was heated at 115 C. for 20 min in a Biotage Initiator microwave reactor with external IR-sensor temperature monitoring from the side of the vessel. The reaction mixture was cooled to RT, diluted with CH2Cl2 and water. The organics were collected using a phase separator and concentrated. The crude product was purified by flash column chromatography using EtOAc/hexanes as eluent to yield the title compound as an off white solid (165 mg, 79%). 1H NMR (400 MHz, CDCl3) delta 8.54 (s, 1H), 8.12 (m, 2H), 7.79 (m, 2H), 7.48 (m, 2H), 7.38 (m, 2H), 1.54 (s, 9H); 19F NMR (376 MHz, CDCl3) 5-58.03; ESIMS m/z 421.3 ([M+H]+).

Reference： [1]Patent: US2014/275563,2014,A1 .Location in patent: Paragraph 0037; 0039
[2]Patent: US2014/275560,2014,A1 .Location in patent: Paragraph 0037; 0038
[3]Patent: US2014/275556,2014,A1 .Location in patent: Paragraph 0036; 0037

53
[ 1184915-33-0 ]
[ 380430-49-9 ]
tert-butyl [4-(2-amino[1,2,4]triazolo[1,5-a]pyrazin-6-yl)phenyl]carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
14.7 g	With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; triphenylphosphine In propan-1-ol for 2h; Reflux;	02.03 tert-butyl [4-(2-amino[1 , 2,4]triazolo[1 , 5-a]pyrazin-6-yl)phenyl]carbamate To a stirred solution of 6-bromo[1,2,4]triazolo[1,5-a]pyrazin-2-amine (10.0 g) in 1-propanol (420 mL) was added 2M potassium carbonate solution (70 mL), f4-[(tert-butoxycarbonyl) amino] phenyl boronic acid (15.6 g), triphenylphosphine (613 mg) and PdCl2(PPh3)2 (3.28 g). The mixture was heatedto reflux for 2h. Water was added and the mixture was stirred at room temperature for 15 minutes. A solid precipitated and was collected by filtration and dried in vacuum to give 14.7 g of the title compound.

Reference： [1]Current Patent Assignee: BAYER AG - WO2014/198594, 2014, A1 Location in patent: Page/Page column 86; 87

54
[ 380430-49-9 ]
[ 1443763-60-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: potassium carbonate; triphenylphosphine; bis-triphenylphosphine-palladium(II) chloride / propan-1-ol / 4 h / Reflux 2: chloro(2-dicyclohexylphosphino-2’,4’,6’-tri-isopropyl-1,1’-biphenyl)[2-(2-aminoethyl)phenyl]palladium(II)methyl-tertbutyl ether; potassium phosphate; XPhos / toluene; 1-methyl-pyrrolidin-2-one / 16 h / Inert atmosphere; Reflux 3: trifluoroacetic acid / dichloromethane / 21 h / 20 °C 4: sodium hydrogencarbonate; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide; dichloromethane / 4 h / 20 °C

Reference： [1]Current Patent Assignee: BAYER AG - WO2014/198647, 2014, A2

55
[ 1159818-57-1 ]
[ 380430-49-9 ]
C₁₅H₁₈N₄O₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 3436 - 3441

56
[ 88497-27-2 ]
[ 380430-49-9 ]
C₁₅H₁₈N₄O₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 3436 - 3441

57
[ 3034-22-8 ]
[ 380430-49-9 ]
C₁₄H₁₇N₃O₂S [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 3436 - 3441

58
[ 380430-49-9 ]
[ 96721-87-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 3436 - 3441

59
[ 380430-49-9 ]
[ 90349-87-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: potassium carbonate; tetrakis(triphenylphosphine) palladium⁽⁰⁾ / water; 1,4-dioxane / 0.33 h / 170 °C 2: trifluoroacetic acid / dichloromethane / 4 h / 20 °C

Reference： [1]Liu, Gang; Abraham, Sunny; Liu, Xing; Xu, Shimin; Rooks, Allison M.; Nepomuceno, Ron; Dao, Alan; Brigham, Daniel; Gitnick, Dana; Insko, Darren E.; Gardner, Michael F.; Zarrinkar, Patrick P.; Christopher, Ron; Belli, Barbara; Armstrong, Robert C.; Holladay, Mark W. [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 17, p. 3436 - 3441]

60
[ 14002-33-6 ]
[ 380430-49-9 ]
C₁₇H₂₇BN₂O₄ [ No CAS ]

Reference： [1]Dalton Transactions,2015,vol. 44,p. 20577 - 20583

61
[ 93131-78-3 ]
[ 380430-49-9 ]
tert-butyl-4-(4-methyl-2-oxo-2H-chromen-7-yl) phenylcarbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With 1,3-bis-(diphenylphosphino)propane; palladium diacetate; tetra-n-butylammoniumfluoride trihydrate; In methanol; 1,2-dimethoxyethane; at 20 - 80℃; for 0.5h;Inert atmosphere; Microwave irradiation;	General procedure: To a solution of 4-methyl-7-nonauorobutylsulfonyloxy coumarin (3b, 1 equiv.) in DME-MeOH (3:1), were added Pd(OAc) 2(0.05 equiv.) and dppp (0.1 equiv.). The solution was purged with nitrogen and stirred at room temperature for 10 min, at which time boronic acid (1.5 equiv.) and TBAF 3H2O (3 equiv.) was added. The reaction solution was purged again with nitrogen and then placed in the microwave and heated for 20-30 min at 80C at 110 W. When TLC and LC-MS showed full consumption of starting materials, the reaction mixture was diluted with ethyl acetate, separated the organic layer, given water wash, brine wash and was dried over anhydrous sodium sulfate and distilled under reduced pressure to get the crude material. The crude product was further puried by column chromatography and eluted in varying polarities to obtain the diaryls 4a-x.

Reference： [1]Journal of Fluorine Chemistry,2016,vol. 182,p. 109 - 120

62
[ 13466-38-1 ]
[ 380430-49-9 ]
tert-butyl (4-(6-oxo-1,6-dihydropyridin-3-yl)phenyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
10.13%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 1h;Inert atmosphere; Microwave irradiation;	To a mixture of <strong>[13466-38-1]5-bromopyridin-2-ol</strong> (600 mg 3.45 mmol) (4- ( (tert-butoxycarbonyl) amino) phenyl) boronic acid (817 mg 3.45 mmol) in water (3 mL) and 1 4-dioxane (9 mL) was added Cs2CO3(2247 mg 6.90 mmol) PdCl2(dppf) (126 mg 0.172 mmol) under N2atmosphere. Then the mixture was stirred and irradiated in a microwave oven at 100 for 1 h. The mixture was concentrated extracted with EA. The organic phase was concentrated. The residue was purified by preparative TLC (DCM/MeOH 10 1) to give tert-butyl (4- (6-oxo-1 6-dihydropyridin-3-yl) phenyl) carbamate (100 mg 0.349 mmol 10.13 yield) 1HNMR(400 MHz CDCl3) delta 7.67 (dd J 2.4 9.6 Hz 1H) 7.43-7.40 (m 1H) 7.35 (d J 8.8 Hz 2H) 7.26 (d J 8.4 Hz 2H) 6.60 (dJ 9.6 Hz 1H) 1.40 (s 9H) ES-LCMS m/z 287.2 (M+H)

Reference： [1]Patent: WO2016/37578,2016,A1 .Location in patent: Page/Page column 142

63
[ 1445993-87-2 ]
[ 380430-49-9 ]
4-bromo-6-methyl-1-tosyl-1H-pyrrolo[2,3-c]pyridin-7(6H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 95℃; for 12h;Inert atmosphere;	A 50 mL vial was charged with a magnetic stir bar, 4-bromo-6-methyl-l-tosyl-lH-pyrrolo[2,3- c]pyridin-7(6H)-one (0.281 g, 0.737 mmol), 1,4-dioxane (3.69 ml, 0.737 mmol), water (0.5 ml, 27.8 mmol), K2C03 (0.306 g, 2.21 1 mmol), 4-(tertbutoxycarbonylamino)phenylboronic acid (0.227 g, 0.958 mmol), and Pd(PPh3)4 (0.085 g, 0.074 mmol). The vial was purged, placed under an atmosphere of nitrogen and heated to 95 C with stirring for 12 h before being allowed to cool to room temperature. The reaction was then diluted with water (20 ml). A precipitate formed which was collected via vacuum filtration using a Buchner funnel. The solids were washed with additional water (2 x 25 mL), dried, and collected. This material was suspended in methanol (~ 5 mL) and treated with KOH (200 mg). After 2 h the MeOH was removed in vacuo and the crude material was suspended in water (~ 20 mL) and the resulting solids were collected via vacuum filtration using a Buchner funnel. The solids were washed with additional water, were collected, and dried in vacuo to afford tert-butyl 4-(6-methyl-7-oxo-6,7-dihydro-lH- pyrrolo[2,3-c]pyridin-4-yl)phenyIcarbamate (362 mg, 0.907 mmol) as a light yellow solid. LCMS M/Z (M+H) 494.

Reference： [1]ACS Medicinal Chemistry Letters,2016,vol. 7,p. 531 - 536
[2]Journal of Medicinal Chemistry,2016,vol. 59,p. 5391 - 5402
[3]Patent: WO2016/77375,2016,A1 .Location in patent: Page/Page column 196

64
[ 1445993-87-2 ]
[ 380430-49-9 ]
tert-butyl 4-(6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-4-yl)phenylcarbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
362 mg		A 50 mL vial was charged with a magnetic stir bar, 4-bromo-6-methyl-1-tosyl-IH- pyrrolo[2,3-cjpyndm-7(6H)-one (0.281 g, 0.737 mmol), 1,4-dioxane (3.69 ml, 0.737 mmol), water (0.5 ml, 27.8 mmol), K2C03 (0.306 g, 2.211 mmol), 4-(tertbutoxycarbonylamino)phenylboronic acid (0.227 g, 0.95 8 mmol), and Pd(PPh3)4 (0.085 g, 0.074 mmol). The vial was purged, placed under an atmosphere of nitrogen and heated to 95 C with stirring for 12 h before being allowed to cool to room temperature. The reaction was then diluted with water (20 ml). A precipitate formed which was collected via vacuum filtration using a Buchner funnel. The solids were washed with additional water (2 x 25 mL),dried, and collected. This material was suspended in methanol (-- 5 mL) and treated with KOH (200 mg). After 2 h the MeOH was removed in vacuo and the crude material was suspended in water (- 20 mL) and the resulting solids were collected via vacuum filtration using a Buchncr funnel. The solids were washed with additional water, were collected, and dried in vacuo to afford tert-butyl 4-(6-methyl-7-oxo-6,7-dihydro- I H-pyrrolo[2,3-c]pyridin-4-yl)phenylcarbainate (362 mg, 0.907 mrnol) as a light yellow solid. LCMS M/Z (M+H) 494.
362 mg	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 95℃; for 12h;Inert atmosphere;	A 50 mL vial was charged with a magnetic stir bar, 4-bromo-6-methyl-l-tosyl-lH-pyrrolo[2,3- c]pyridin-7(6H)-one (0.281 g, 0.737 mmol), 1,4-dioxane (3.69 ml, 0.737 mmol), water (0.5 ml, 27.8 mmol), K2C03 (0.306 g, 2.21 1 mmol), 4-( ter/-butoxycarbonyl-amino)phenylboronic acid (0.227 g, 0.958 mmol), and Pd(PPh3)4 (0.085 g, 0.074 mmol). The vial was purged, placed under an atmosphere of nitrogen and heated to 95 C with stirring for 12 h before being allowed to cool to room temperature. The reaction was then diluted with water (20 ml). A precipitate formed which was collected via vacuum filtration using a Buchner funnel. The solids were washed with additional water (2 x 25 mL), dried, and collected. This material was suspended in methanol (~ 5 mL) and treated with KOH (200 mg). After 2 h the MeOH was removed in vacuo and the crude material was suspended in water (~ 20 mL) and the resulting solids were collected via vacuum filtration using a Buchner funnel. The solids were washed with additional water, were collected, and dried in vacuo to afford iert-butyl 4-(6-methyl-7-oxo-6,7-dihydro-lH- pyrrolo[2,3-c]pyridin-4-yl)phenylcarbamate (362 mg, 0.907 mmol) as a light yellow solid. (0726) LCMS M/Z (M+H) 494
362 mg	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 95℃; for 12h;Inert atmosphere;	A 50 mL vial was charged with a magnetic stir bar, 4-bromo-6-methyl-1-tosyl-1H-pyrrolo[2,3-c]pyridin-7(611)-one (0.28 1 g, 0.737 mmol), 1,4-dioxane (3.69 ml, 0.737 mmol), water (0.5 ml,27.8 mmol), K2C03 (0.306 g, 2.211 mmol), 4-(tertbutoxycarbonylamino)phenylboronic acid(0.227 g, 0.958 mmol), and Pd(PPh3)4 (0.085 g, 0.074 mmol). The vial was purged, placed under an atmosphere of nitrogen and heated to 95 C with stirring for 12 h before being allowed to cool to room temperature. The reaction was then diluted with water (20 ml). A precipitate formed which was collected via vacuum filtration using a Buchner funnel. The solids were washed with additional water (2 x 25 mL), dried, and collected. This material was suspended inmethanol (- 5 mL) and treated with KOH (200 mg). After 2 h the MeOH was removed in vacuo and the crude material was suspended in water ( 20 mL) and the resulting solids were collected via vacuum filtration using a Buchner funnel. The solids were washed with additional water, were collected, and dried in vacuo to afford tert-butyl 4-(6-methyl-7-oxo-6,7-dihydro-1H- pyrrolo[2,3-c]pyridin-4-yl)phenylcarbamate (362 mg, 0.907 mmol) as a light yellow solid.LCMS MIZ (M+H) 494.

Reference： [1]Patent: WO2016/77378,2016,A1 .Location in patent: Page/Page column 157; 161; 167
[2]Patent: WO2016/77380,2016,A1 .Location in patent: Page/Page column 97; 101
[3]Patent: WO2016/123391,2016,A1 .Location in patent: Page/Page column 185; 189

65
[ 13676-02-3 ]
[ 380430-49-9 ]
t-butyl (4-(6-methoxyquinolin-2-yl)phenyl)carbamate [ No CAS ]

Reference： [1]ACS Chemical Neuroscience,2016,vol. 7,p. 897 - 911

66
[ 1413732-47-4 ]
[ 380430-49-9 ]
[ 1333415-86-3 ]

Yield	Reaction Conditions	Operation in experiment
93%	With oxygen; In 1-methyl-pyrrolidin-2-one; at 20℃; for 1h;	General procedure: Arylboronic acid 2 (0.12 mmol) and (bpy)Cu(SCF3) 1 (0.1 mmol) were added to a Schlenk flask fitted with magnetic stir bar and O2 balloon. The flask was evacuated and back filled with O2. The solvent NMP (2.0 mL) was added by syringe at room temperature and the solution was stirred for 1 h. For the products reported with isolated yields (3a, 3k, 3l, 3m, 3n, 3o, 3p, 3q, 3r, 3s, 3t, 3u and 3w), the reaction mixture was diluted with EtOAc, then washed with water and brine. The organic phase was dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by flash chromatography on silica gel (n-hexane/ethyl acetate gradient) to afford the desired compounds. Gram-scale synthesis of compound 5 was prepared following the similar procedure. The relatively volatile products (3b, 3c, 3d, 3e, 3f, 3g, 3h, 3i, 3j and 3v) were not isolated and their yields were determined by 19F NMR measurement in CDCl3 of the reaction mixture. For the products reported with 19F NMR yields, PhOCF3 (1.0 equiv) was added to the reaction mixture as internal standard added after the reaction completed. The reaction mixture was purified by flash chromatography on silica gel (pentane/diethyl ether gradient) to afford the desired compounds.

Reference： [1]Journal of Fluorine Chemistry,2017,vol. 194,p. 73 - 79

67
[ 380430-49-9 ]
[ 18437-66-6 ]

Yield	Reaction Conditions	Operation in experiment
94%	With N-chloro-succinimide In acetonitrile at 80℃; for 12h;

Reference： [1]He, Wen; Zhang, Rongli; Cai, Mingzhong [RSC Advances, 2017, vol. 7, # 2, p. 764 - 770]

68
C₉H₉BrN₂O₃S [ No CAS ]
[ 380430-49-9 ]
tert-butyl [3'-(1,1-dioxido-4-oxo-1,2,5-thiadiazolidin-2-yl)-4'-methyl[1,1'-biphenyl]-4-yl]-carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; In 1,2-dimethoxyethane; water; at 100℃;Inert atmosphere; Sealed tube;	To a solution of 1b (265 mg, 0.868 mmol)and <strong>[380430-49-9]{4-[(tert-butoxycarbonyl)amino]phenyl}boronic acid</strong> (247mg, 1.04 mmol) in 30 mL of 1,2-dimethoxyethane and water[2:1 (v/v)] in an oven-dried Pyrex tube equipped with a stir barwas added K2CO3 (480 mg, 3.47 mmol). The reaction mixturewas degassed by being bubbled with nitrogen gas for 5 minbefore the addition of Pd(PPh3)2Cl2 (30 mg, 0.04 mmol),followed by degassing for an additional 1 min. The tube wasthen sealed and heated at 100 C while its contents were beingstirred for 16 h. The Pd catalyst was removed by filtration andthe filtrate concentrated in vacuo to remove 1,2-dimethoxyethane.The solid product obtained in this manner wascollected by filtration and washed with ethyl acetate to give 3as a pale yellow solid (320 mg, 88%): 1H NMR (acetone-d6,300 MHz) delta 7.75 (d, J = 2.0 Hz, 1H), 7.56 (dt, J = 9.0, 2.0 Hz,2H), 7.51 (d, J = 9.0 Hz, 2H), 7.48 (dd, J = 9.0, 2.0 Hz, 1H),7.33 (d, J = 9.0 Hz, 1H), 4.26 (s, 2H), 2.44 (s, 3H), 1.52 (s,9H); 13C NMR (acetone-d6, 75 MHz) delta 176.3, 154.7, 140.6,140.1, 138.5, 138.3, 135.4, 132.3, 128.0, 127.7, 126.9, 119.7,80.6, 60.4, 28.7, 18.2; HRMS (ESI-TOF, [M + H]+) calcd forC20H24N3O5S m/z 418.1437, found m/z 418.1433.

Reference： [1]Biochemistry,2017,vol. 56,p. 2051 - 2060

69
4-bromo-N,N,1-trimethyl-1H-pyrrole-2-carboxamide [ No CAS ]
[ 380430-49-9 ]
tert-butyl (4-(5-(dimethylcarbamoyl)-1-methyl-1H-pyrrol-3-yl)phenyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In water; acetonitrile; at 100℃; for 0.1h;Inert atmosphere; Microwave irradiation;	General procedure: Exam ples 60 -61: -Synthesis of am ido m pb derivatives (26.29) (0821) In a microwave vial were sequentially added the corresponding bromo pyrrole carboxamide 43 (0.400 g, 1.73 mmols) or 44 (0.484 g, 1.87 mmols), (4-((tert- butoxycarbonyl)amino)phenyl)boronic acid (1.1 equiv.), K2C03 (3 equiv.), ACN (15 mL) and H20 (13 mL). The reaction mixture was left under magnetic stirrer in N2 atmosphere for 5 minutes. At that point Tetrakis Pd (0.05 equiv.) was added. The reaction mixture was then heated at MW radiation at 1000 C for 6 minutes. LC-MS showed the formation of the product. At that point the reaction mixture was filtered under vacuum through a path of celite previously washed with AcOEt. The resulting solution, brown in colour, was then evaporated using a rotary evaporator. At that point the reaction mixture was purified by column chromatography (mobile phase: (0822) DCM/AcOEt, 80/20, v/v) giving pure compounds 45 and 46.

Reference： [1]Patent: WO2017/98257,2017,A1 .Location in patent: Page/Page column 97; 98

70
1,1,1,3,3,3-hexafluoro-2-(3-fluoro-4-iodophenyl)propan-2-ol [ No CAS ]
[ 380430-49-9 ]
tert-butyl (2'-fluoro-4'-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-[1,1'-biphenyl]-4-yl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 80℃; for 5h;Inert atmosphere; Sealed tube;	Step (c): To a solution of 1,1,1,3,3,3-hexafluoro-2-(3-fluoro-4-iodophenyl)propan- 2-ol (6.2 g, 16 mmol) in 1,4-dioxane (100 mL) and water (20 mL) was added (4-((tert- butoxycarbonyl)amino)phenyl)boronic acid (4.2 g, 17.6 mmol), followed by addition of potassium carbonate (6.6 g, 48 mmol) and Pd(PPh3)4 (0.9 g, 0.78 mmol), the vessel was purged with argon, sealed and heated to 80 for 5h. Added water, extracted with ethyl acetate, the organic layer was washed with brine and dried over Na2SO4. The solid was filtered off, and the filtrate was concentrated under reduced pressure. The resulting crude product was purified by silica gel chromatography with petroleum ether/ethyl acetate (20/1, v/v) to yield tert-butyl(2'-fluoro-4'-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-[1,1'- biphenyl]-4-yl)carbamate (5.35 g, 74 % yield).1H NMR (400 MHz, CDCl3) delta 7.54- 7.44 (m, 6H), 7.40 (d, J = 8.4 Hz, 1H), 6.57 (s, 1H), 3.82 (s, 1H), 1.53 (d, J = 3.2 Hz, 9H).
74%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water;Inert atmosphere; Reflux;	The compound 2-(4-iodo-3-fluorophenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (6.2 g, 16 mmol) was obtained.Soluble in 1,4-dioxane (100 mL) and water (20 mL).To this solution was added 4-(N-BOC-amino)benzeneboronic acid (4.2 g, 17.6 mmol)Potassium carbonate (6.6 g, 48 mmol) and Pd(PPh3) 4 (0.9 g, 0.78 mmol) were argon-protected and refluxed overnight.The reaction was monitored by TLC. After the reaction was completed, water was added, ethyl acetate (3×50 mL), and the organic phase was washed once with brine.Dry over anhydrous sodium sulfate and spin dry the organic phase.The crude product was separated on silica gel column (PE: EA = 20:1) to afford 5.4 g (yield: 74%).

Reference： [1]Patent: WO2017/127442,2017,A1 .Location in patent: Paragraph 0190
[2]Journal of Medicinal Chemistry,2019,vol. 62,p. 4716 - 4730
[3]Patent: CN109879784,2019,A .Location in patent: Paragraph 0054; 0062-0064

71
ansamitocin P-3 [ No CAS ]
[ 380430-49-9 ]
C₄₃H₅₇N₃O₁₁ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
35%	With potassium phosphate; (2-dicyclohexylphosphino-2?,4?,6?-triisopropyl-1,1 ?-biphenyl)[2-(2?-amino-1,1?-biphenyl)]palladium(II) methanesulfonate; In tetrahydrofuran; at 40℃; for 2h;Inert atmosphere; Sealed tube;	Compound 1 4-(N-Boc amino)phenyl boronic acid (18.7 mg), was added to solid AP3 2 (32.6 mg), with potassium phosphate tribasic (32.7 mg) and the palladium catalyst Sphos Pd G3 (1 mg) commercially available from Sigma-Aldrich. The solids were purged with Ar 3x and dry THF (150 mu) added to the mixture. Ar was then bubbled through the reaction mixture for 60 sec, the reaction vessel was sealed and heated at 40 C for 2 h, at which point the reaction was deemed complete by LC/MS. The reaction mixture was then filtered through a short pad of Si02, washed with Et20 and concentrated. The mixture was then purified by preparative HPLC (Gemini 150 x 30 mm column) (5?95% ACN in H20, each containing 0.05% AcOH) and desired fractions lyophilized to afford 3 as a white crystalline solid (14.3 mg, 35% yield). NMR (500MHz ,CHLOROFORM-d) delta = 7.41 (d, J= 7.3 Hz, 2 H), 7.06 (d, J= 8.8 Hz, 2 H), 6.88 (dd, J= 1.5, 10.7 Hz, 2 H), 6.58 - 6.46 (m, 2 H), 6.27 - 6.18 (m, 2 H), 5.49 (dd, J= 9.0, 15.4 Hz, 1 H), 4.85 (dd, J= 2.9, 12.2 Hz, 1 H), 4.36 - 4.28 (m, 1 H), 3.83 (s, 3 H), 3.61 - 3.52 (m, 2 H), 3.39 (s, 3 H), 3.28 (d, J= 13.2 Hz, 1 H), 3.09 - 2.95 (m, 3 H), 2.70 - 2.68 (m, 3 H), 2.65 (quin, J= 7.0 Hz, 1 H), 2.25 (dd, J= 2.9, 13.7 Hz, 1 H), 1.77 (s, 3 H), 1.70 (d, J= 13.2 Hz, 1 H), 1.55 (s, 9 H), 1.33 (d, J= 6.3 Hz, 3 H), 1.28 (d, J= 7.3 Hz, 3 H), 1.22 (d, J= 6.8 Hz, 3 H), 0.96 (s, 3 H); LC/MS: retention time 3.49 min (Merck Chromolith RP-18e analytical HPLC column (monolithic, 50 < 2 mm); analytical HPLC method: injection volume 5 mu; flow rate 1 mL/min; 5?95% acetonitrile in water over 5 mins; Agilent diode array detector at lambda = 254, or 220 nm; room temperature), (ES+) calc for C43H58N30u: [M+H] + 792; found 792.

Reference： [1]Patent: WO2018/51109,2018,A1 .Location in patent: Page/Page column 66-67

72
(R)-5-iodo-N-(1-phenylethyl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine [ No CAS ]
[ 380430-49-9 ]
tert-butyl-(R)-(4-(4-((1-phenylethyl)amino)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d] pyrimidin-5-yl)phenyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With potassium carbonate; XPhos; In 1,4-dioxane; water; at 100℃; for 0.166667h;Inert atmosphere;	General procedure: To a mixture of the selected arylboronic acid (0.610mmol, 1.2 equiv.), K2CO3 (1.53mmol, 3 equiv.), XPhos (0.0250mmol, 0.05 equiv.), 2nd generation XPhos pre-catalyst (0.0250mmol, 0.05 equiv.), and the selected 4-amino-5-iodo-7H-pyrrolo [2,3-d]pyrimidine (0.511mmol, 1 equiv.) in 1,4-dioxane (3mL) was added water (3mL) under a nitrogen atmosphere. The reaction mixture was stirred at 100C until complete conversion. The solvent was removed before water (15mL) and EtOAc (25mL) were added, the phases were separated and the water phase was extracted with more EtOAc (3×20mL). The combined organic phases were washed with brine (20mL), dried over Na2SO4, filtered and concentrated. Purification was as stated for each individual compound.
89%	With chloro(2-dicyclohexylphosphino-2?,4?,6?-triisopropyl-1,1?-biphenyl)[2-(2?-amino-1,1?-biphenyl?)]palladium(II); potassium carbonate; XPhos; In 1,4-dioxane; water; at 100℃; for 0.166667h;Inert atmosphere;	General procedure: To a mixture of the selected arylboronic acid (0.610 mmol, 1.2equiv.), K2CO3 (1.53 mmol, 3 equiv.), XPhos (0.0250 mmol, 0.05equiv.), 2nd generation XPhos pre-catalyst (0.0250 mmol, 0.05 equiv.),and the selected 4-amino-5-iodo-7H-pyrrolo[2,3-d]pyrimidine(0.511 mmol, 1 equiv.) in 1,4-dioxane (3 mL) was added water (3 mL)under a nitrogen atmosphere. The reaction mixture was stirred at100 C until complete conversion. The solvent was removed beforewater (15 mL) and EtOAc (25 mL) were added, the phases were separatedand the water phase was extracted with more EtOAc (3×20 mL).The combined organic phases were washed with brine (20 mL), driedover Na2SO4, filtered and concentrated. Purification was as stated foreach individual compound.

Reference： [1]European Journal of Medicinal Chemistry,2018,vol. 155,p. 562 - 578
[2]Bioorganic Chemistry,2019,vol. 88

73
[ 216699-86-4 ]
[ 380430-49-9 ]
tert-butyl (4-(6,7-dimethoxyquinoxalin-2-yl)phenyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In water; acetonitrile; at 100℃; for 3h;	[0625] Procedure: To a stirred solution of 2-chloro-6,7-dimethoxyquinoxaline (0.2 g, 0.89 mmol) in acetonitrile (9mL) and water (3mL) was added <strong>[380430-49-9](4-((tert-butoxycarbonyl)amino)phenyl)boronic acid</strong> (0.23 g, 0.98 mmol), and sodium carbonate (0.28 g, 2.67mmol). The resulting mixture was degassed for 15 min with argon and added Pd(PPh3)4 (0.051 g, 0.044 mmol) degassed for another 10 min. Resulting mixture was stirred for 3h at 100 C. Progress of the reaction was monitored by TLC. Reaction mixture was filtered through celite bed and filtrate was diluted with ethyl acetate (20mL), washed with water (2 x 10mL) followed by brine (10mL), dried over anhydrous sodium sulphate, filtered and evaporated under reduced pressure to give crude product. The crude product was purified by combiflash using 40% ethyl acetate in hexane to afford tert-butyl (4-(6,7-dimethoxyquinoxalin-2-yl)phenyl)carbamate as off-white solid (0.4 g, 73%).1HNMR (400 MHz, DMSO-d6): delta 9.58 (s, 1H), 9.26 (s, 1H), 8.17 (d, J = 8.8 Hz, 2H), 7.62 (d, J = 8.8 Hz, 2H), 7.40 (d, J = 5.2 Hz, 2H), 4.02 (s, 3H), 4.00 (s, 3H), 1.49 (s, 9H); LCMS (ES) m/z = 382.1 [M+H]+ .

Reference： [1]Patent: WO2019/46778,2019,A1 .Location in patent: Paragraph 0625

74
[ 6630-33-7 ]
[ 380430-49-9 ]
[ 870703-82-5 ]

Yield	Reaction Conditions	Operation in experiment
86%		A solution of 2-bromobenzaldehyde (1.08 mmol), 4-boc-aminophenylboronic acid (1.19 mmol) and potassium carbonate (3.24 mmol) in a 0.1 M solvent mixture of ethanol:toluene:water (9:3:1) was stirred at room temperature for 5 minutes under nitrogen. Tetrakis(triphenylphosphine)pallaidum(0) (0.108 mmol) was then added and the mixture was stirred under microwave irradiation at 100 C for 20 minutes. The mixture was then filtered through a pad of celite and concentrated in vacuo. The crude sample was redissolved in DCM and water, and transferred to a separatory funnel. The two layers were partitioned and the aqueous layer was extracted with DCM (3X). The collected organic layers were then washed once with saturated NaCl solution, dried over MgSO4 and concentrated in vacuo. The crude sample was absorbed onto a small amount of silica and purified using flash chromatography using a Hexane:EtOAc gradient. tert-butyl (2'-formyl-[1,1'-biphenyl]-4-yl)carbamate was isolated as an oil (86%).1H NMR (400 MHz, CDCl3) delta 10.01 (s, 1H), 8.03- 8.01 (dd, J = 7.8, 1.4 Hz, 1H), 7.65- 7.61 (td, J = 7.5, 1.5 Hz, 1H), 7.54- 7.42 (m, 4H), 7.33- 7.31 (d, J = 8.5 Hz, 2H), 6.88 (s, 1H), 1.55 (s, 9H).

Reference： [1]Patent: WO2019/56120,2019,A1 .Location in patent: Paragraph 00134; 00206; 00207

75
[ 625-92-3 ]
[ 380430-49-9 ]
tert-butyl (4-(5-bromopyridin-3-yl)phenyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; water; at 100℃; for 1h;Inert atmosphere;	A mixture of <strong>[380430-49-9](4-((tert-butoxycarbonyl)amino)phenyl)boronic acid</strong> (5.00 g, 21.1 mmol), 3,5-dibromopyridine (7.49 g, 31.6 mmol), Pd(dppf)Cl2 (1.54 g, 2.11 mmol) and Na2C03 (6.71 g, 63.3 mmol) in dioxane (40 mL) and water (10 mL) was degassed and purged with N2 for 3 times. And the resulting reaction mixture was stirred at 100 C for 1 hour under N2 atmosphere. A black suspension was formed. LCMS showed the purity of the desired product is 52% (Rt = 0.971 min; MS Calcd: 348.1; MS Found: 348.9 [M+H]+). The reaction mixture was filtered through a pad of celite and the solid was washed with EtOAc (200 mL) to give a filtrate, which was diluted with water (100 mL). The aqueous layer was extracted with EtOAc (50 mL x2). The combined organic layer was washed with water (60 mL x2), brine (60 mL), dried over anhydrous Na2S04, filtered and concentrated under reduced pressure. The residue was purified by Combi Flash (0% to 30% EtOAc in PE) to give tert-butyl (4-(5- bromopyridin-3-yl)phenyl)carbamate (4.55 g, yield: 62%) as a white solid. NMR (400 MHz, CDCb) d 1.54 (9H, s), 6.58 (1H, brs), 7.45-7.56 (4H, m), 7.99 (1H, t, J = 2.0 Hz), 8.62 (1H, d, J= 1.8 Hz), 8.73 (1H, d , J= 1.8 Hz).

Reference： [1]Patent: WO2019/126733,2019,A1 .Location in patent: Paragraph 0743; 0755

76
[ 1196-90-3 ]
[ 380430-49-9 ]
[ 864076-03-9 ]

Reference： [1]Patent: WO2019/133652,2019,A1

77
[ 912773-24-1 ]
[ 380430-49-9 ]
tert-butyl (4-(imidazo[1,2-a]pyrazin-6-yl)phenyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76.2%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,2-dimethoxyethane; water; at 80℃; for 12h;Inert atmosphere;	To a solution of <strong>[912773-24-1]6-bromoimidazo[1,2-a]pyrazine</strong> 16 (2.0 g, 10.1 mmol) and (4-((tert-butoxycarbonyl)amino)phenyl) boronic acid (3.5 g, 14.8 mmol) in DME aqueous solution (DME : H2O = 2 : 1, 100 mL), were added Pd(PPh3)4 (578 mg, 0.5 mmol) and K2CO3 (2.8 g, 20.2 mmol). The solution was degassed with argon for 5 min and then stirred at 80 for 12 h. The reaction suspension was cooled to room temperature and filtered through Celite. The solvent was removed by rotary evaporation, the residue was treated with water and extracted with ethyl ether, then washed with brine, dried over by magnesium sulfate. The organic layer was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (MeOH/DCM, v/v = 1:100) to afford tert-butyl (4-(imidazo[1,2-a]pyrazin-6-yl)phenyl)carbamate (2.4 g, 7.7 mmol) as yellow solid, yielded 76.2%. 1H NMR (400 MHz, DMSO-d6) delta 9.46 (s, 1H), 9.09 (s, 1H), 9.06 (s, 1H), 8.03 (s, 1H), 7.90 (d, J = 8.8 Hz, 2H), 7.81 (s, 1H), 7.56 (d, J = 8.8 Hz, 2H), 1.47 (s, 9H). LC-MS (ESI) m/z 311 [M + H] +.

Reference： [1]European Journal of Medicinal Chemistry,2019,vol. 179,p. 470 - 482

78
[ 912773-24-1 ]
[ 380430-49-9 ]
tert-butyl (4-(3-bromoimidazo[1,2-a]pyrazin-6-yl)phenyl)carbamate [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2019,vol. 179,p. 470 - 482

79
1-[4-bromo-2-(hept-1-yn-1-yl)phenyl]-3-ethyl-3-phenyltriaz-1-ene [ No CAS ]
[ 380430-49-9 ]
tert-butyl [4'-(3-ethyl-3-phenyltriaz-1-en-1-yl)-3'-(hept-1-yn-1-yl)-[1,1'-biphenyl]-4-yl]carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With potassium phosphate; tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 100℃; for 2.5h;Sealed tube; Inert atmosphere;	General procedure: Triazene 3 or azidocinnoline 5 (1 equiv), ArB(OH)2 6 (1.5 equiv), K3PO4 (2 equiv), and Pd(PPh3)4(5 mol %) were placed in a vial. The vial was sealed, and the mixture was evacuated and flushed withAr several times. 1,4-Dioxane (C = 0.1 M) was added, and the vial with the reaction mixture was placedin a preheated oil bath (80100 C) and stirred for 120 h (TLC control). After cooling to rt, the reactionmixture was ltered through a pad silica gel and washed with ethyl acetate. Solvents were removedunder reduced pressure, and the crude product was purified by column chromatography on silica gel.

Reference： [1]Molecules,2019,vol. 24

80
[ 1105662-87-0 ]
[ 380430-49-9 ]
methyl(Z)-4-((tert-butoxycarbonyl)(methyl)amino)-3-(4-((tert-butoxycarbonyl)amino)phenyl)but-2-enoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%	With tert-Amyl alcohol; chlorobis(cyclooctene)rhodium(I) dimer; 1,3-bis(bis(4-(trifluoromethyl)phenyl)phosphino)propane; sodium t-butanolate at 110℃; for 8h; Schlenk technique; Inert atmosphere;

Reference： [1]Yang, Xuan; Kong, Wei-Yu; Gao, Jia-Ni; Cheng, Li; Li, Nan-Nan; Li, Meng; Li, Hui-Ting; Fan, Jun; Gao, Jin-Ming; Ouyang, Qin; Xie, Jian-Bo [Chemical Communications, 2019, vol. 55, # 84, p. 12707 - 12710]

81
C₁₉H₁₅BiO₅S₂ [ No CAS ]
[ 380430-49-9 ]
C₂₃H₂₂BiNO₄S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In water; toluene; at 60℃; for 2h;	General procedure: A suspension of bismacycle tosylate 1-OTs (1.0 equiv.; initial concentration = 0.05 M),K2CO3 (1.2 equiv.) and arylboronic acid (1.1 equiv.) in toluene/water (99:1,v/v) was stirred at 60 C for 2 h

Reference： [1]Nature Chemistry,2020,vol. 12,p. 260 - 269

82
[ 920006-32-2 ]
[ 15813-08-8 ]
[ 76513-69-4 ]
(2S)-2-(tert-butoxycarbonylamino)-3,3-dicyclopropyl-propanoic acid [ No CAS ]
[ 380430-49-9 ]
(S)-N-(1,1-dicyclopropyl-3-((4-(4-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-5-yl)phenyl)amino)-3-oxopropan-2-yl)-1-isopropyl-1H-pyrazole-5-carboxamide [ No CAS ]
(S)-N-(1,1-dicyclopropyl-3-((4-(5-methyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-4-yl)phenyl)amino)-3-oxopropan-2-yl)-1-isopropyl-1H-pyrazole-5-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 5-bromo-4-methyl-1H-imidazole; (2-trimethylethylsilylethoxy)methyl chloride With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 2h; Stage #2: [4-(tert-butoxycarbonylamino)phenyl]boronic acid With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium carbonate In water; N,N-dimethyl-formamide at 110℃; for 16h; Inert atmosphere; Stage #3: 1-(1-methylethyl)-1H-pyrazole-5-carboxylic acid; (2S)-2-(tert-butoxycarbonylamino)-3,3-dicyclopropyl-propanoic acid Further stages;	288; 297; 298; 326 Preparation 5 N-[(lS)-l-cyclohexyl-2-[4-[3,5-dimethyl-l-(2-trimethylsilylethoxymethyl)pyrazol-4- yl]anilino]-2-oxo-ethyl]-2-methyl-pyrazole-3-carboxamide General procedure: To a stirred solution of the imidazole of Preparation 285A (100 mg, 0.52 mmol) in DMF (1 mL) was added 60% NaH (15 mg, 0.63 mmol) followed by SEM-CI (0.1 mL, 0.58 mmol) at 0°C. The resulting reaction mixture was stirred at 0°C for 2 hours, then poured into ice cold water (100 mL) and extracted with EtOAc (2 x 50 mL). The combined organic layers were washed with water (2 x 30 mL), brine (30 mL), dried over anhydrous Na2SC>4 and concentrated under reduced pressure. The obtained crude compound was purified by silica gel (100-200 mesh) column chromatography (10%-20% EtOAc in pet ether as eluent) to afford a mixture of the title compounds (120 mg, 75 %) as a yellow liquid. 1H NMR (400 MHz, Chloroform-d) d 7.54 (s, 0.65H), 7.41 (s, 0.35H), 5.30 (s, 0.5H).5.22 (s, 1.5H), 3.63- 3.59 (m, 1H), 3.54-3.48 (m, 2H), 0.96-0.84 (m, 4H), -0.003 (s, 9H); LCMS (METHOD 5) (ESI) : m/z: 317 [M + H+]; RT = 2.56 min and 2.69 min; (ACQUITY BEH C18 column, 0.05% FA in water with MeCN). To a stirred solution of (4-((tert-butoxycarbonyl)amino)phenyl)boronic acid (100 mg, 0.344 mmol) and the bromides of Preparation 288 (98 mg, 0.41 mmol) in DMF (5 mL) and water (0.5 ml) was added K2CO3 (71 mg, 0.51 mmol) at room temperature. The resulting reaction mixture was purged with argon for 15 min and then Pd(dppf)Cl2.CH2Cl2 (14 mg, 0.017mmol) was added. The reaction mixture was heated at 110°C for 16 hours then cooled to room temperature, diluted with water (20 mL) and extracted with EtOAc (2 x 30 mL). The combined organic layers were washed with water (20 mL) and brine (20 mL), dried over anhydrous Na2S04, filtered and concentrated under reduced pressure to afford the title compounds (150 mg, crude) as a brown liquid. 1H NMR (400 MHz, Chloroform-d) d 7.60-7.57 (d, J = 8.0 Hz, 2H), 7.55 (s, 1H), 7.45-7.43 (d, J = 8.0 Hz, 2H), 6.55, 6.48 (br s, 1H), 5.24, 5.19 (s, 2H), 3.53-3.44 (m, 2H), 2.43, 2.21 (s, 3H), 1.52 (s, 9H), 0.93-0.85 (m, 2H), -0.013 (s, 9H); LCMS (METHOD 5) (ESI) : m/z: 404 [M + H+]; RT = 2.35 min (ACQUITY BEH C18 column, 0.05% FA in water with MeCN). To a stirred solution of the compounds of Preparation 297 (50 mg, 0.10 mmol) in MeOH (1 mL) was added 4M HCI in 1,4-dioxane (1 mL) at 0°C. The resulting reaction mixture was stirred at room temperature for 30 min then concentrated under reduced pressure and dried give the title compounds (80 mg, crude) as a brown liquid. This was used as such for the next step without further purification. 1H NMR (300 MHz, Chloroform-d) d 9.36-9.34 (d, J= 8.8 Hz, 1H), 7.55-7.48 (m, 2H), 7.36-7.33 (d, J = 8.1 Hz, 1H) 7.12-7.09, 7.03-7.00(d, J = 8.4 Hz, 2H), 5.59, 5.39 (s, 1H), 3.63-3.46 (m, 2H), 2.43, 2.24 (s, 3H), 0.93-0.78 (m, 2H), -0.01, -0.04 (s, 9H); LCMS (METHOD 5) (ESI) : m/z: 304 [M + H+]; RT= 1.60 min & 1.66 min; (ACQUITY BEH C18 column, 0.1% FA in water with MeCN). DIPEA (3.07 mL, 2.28 g, 17.6 mmol) was added to a stirred solution of (2S)-2-(tert- butoxycarbonylamino)-2-cyclohexyl-acetic acid (1.51 g, 5.87 mmol) in DMF (25 mL) followed by the amine of Preparation 2 (1.86 g, 5.87 mmol). The mixture was stirred for 5 minutes to ensure complete dissolution and HATU (2.45 g, 6.46 mmol) was then added. After 5 minutes the temperature had risen from 22°C to 28°C. After 75 min the reaction was concentrated to approximately 5 mL in vacuo and the residue was diluted with EtOAc (50 mL), washed with water (50 mL), 10% aq. K2CO3 (50 mL) and brine (50 mL), dried (MgSCU) and evaporated. The crude product was purified by column chromatography (silica gel, eluting with 0-50% EtOAc in heptane) to give the title compound as a yellow foam (3.03 g, 89%). 1H NMR (300 MHz, Chloroform-d) d 8.11 (s, 1H), 7.69 - 7.49 (m, 2H), 7.23 - 7.17 (m, 2H), 5.39 (s, 2H), 5.17 (d, J = 8.7 Hz, 1H), 4.09 - 3.98 (m, 1H), 3.69 - 3.56 (m, 2H), 2.29 (s, 3H), 2.23 (s, 3H), 2.00 - 1.62 (m, 6H), 1.48 (s, 9H), 1.37 - 1.01 (m, 5H), 0.97 - 0.87 (m, 2H), 0.00 (s, 9H) ); LCMS (ES) : m/z 557.7 [M + H]+, RT = 1.02 min. Tert-butyl N-[( lS)-l-cyclohexyl-2-[4-[3, 5-dimethyl- l-(2-trimethylsilylethoxymethyl)- pyrazol-4-yl]anilino]-2-oxo-ethyl]carbamate from Preparation 3 (2.25 g, 4.04 mmol) was dissolved in MeOH (10 mL) and 4M HCI in dioxane (20 ml_, 80 mmol) was added. After 90 minutes the reaction was diluted with MeOH (10 mL) and concentrated in vacuo. The residue was treated with DCM (30 mL) and concentrated in vacuo (twice), then dried in vacuo to give the target compound as a pale yellow foam that was used without further purification. LCMS (ES): m/z 457.6 [M + H]+, RT = 0.73 min. DIPEA (4.14 ml_, 3.13 g, 24.2 mmol) was added to a solution of the compound of Preparation 4 (4.04 mmol) in DMF (20 ml_). The yellow solution was cooled in an ice bath and 2-methylpyrazole-3-carboxylic acid (612 mg, 4.85 mmol) was added followed by HATU (2.0 g, 5.25 mmol). After the initial exothermic reaction had ended the ice bath was removed. The yellow solution was stirred at room temperature for 1 hour then poured into a mixture of sat. aq. sodium bicarbonate solution (25 mL) and water (200 ml_). This was extracted with EtOAc (2 x 150 mL) and the combined organic phases were washed with brine (200 mL), dried (NazSCU) and evaporated. The crude product was purified by column chromatography (silica gel, eluting with DCM/MeOH 99: 1 to DCM/MeOH 98:2) to give the title compound (2.06 g, 86%) as a pale red solid. 1H NMR (300 MHz, Chloroform-d) d 8.06 (s, 1H), 7.66 - 7.53 (m, 2H), 7.46 (d, J = 2.1 Hz, 1H), 7.26 - 7.19 (m, 2H), 6.84 (d, J = 8.6 Hz, 1H), 6.64 (d, J = 2.1 Hz, 1H), 5.39 (s, 2H), 4.51 (t, J = 8.1 Hz, 1H), 4.17 (s, 3H), 3.70 - 3.58 (m, 2H), 2.30 (s, 3H), 2.23 (s, 3H), 2.12 - 1.63 (m, 6H), 1.42 - 1.06 (m, 5H), 0.99 - 0.86 (m, 2H), 0.00 (s, 9H); LCMS (METHOD 3) (ES) : m/z 565.7 [M + H]+, RT = 0.93 min.

Reference： [1]Current Patent Assignee: LEO FONDET - WO2020/127685, 2020, A1 Location in patent: Page/Page column 33-35; 154; 155; 159-160; 173

83
[ 16498-85-4 ]
[ 380430-49-9 ]
methyl 2-(4-((tert-butoxycarbonyl)amino)phenyl)quinoline-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68.8%	Stage #1: methyl 2-chloroquinoline-3-carboxylate; [4-(tert-butoxycarbonylamino)phenyl]boronic acid With tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate In water; N,N-dimethyl-formamide at 50℃; for 5h; Inert atmosphere; Stage #2: With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride In water; N,N-dimethyl-formamide at 50℃; for 5h;	2.a Synthesis of (2R,3S)-2-(4-(cyclopentylamino)phenyl)-l-(2-fluoro-6-methylbenzoyl)-N-(4- (hy droxymethyl)-3 -(trifluoromethyl)phenyl)- 1,2,3 ,4-tetrahy droquinoline-3 -carboxamide(INFO 15) a) To a solution of methyl 2-chloroquinoline-3-carboxylate (25.0 g, 112 mmol) in DMF (250 mL) was added [4-(tert-butoxycarbonylamino)phenyl]boronic acid (32.0 g, 135 mmol). Na2C03 (35.8 g, 338 mmol) in H20 (100 mL) was then added followed by Pd(PPh3)4 (13.0 g, 11.2 mmol) was added. The mixture was stirred at 50 °C under N2 for 5 hrs. Then Pd(dppf)Cl2 (8.25 g, 11.2 mmol) was added. The mixture was stirred at 50 °C for 5 hrs. LCMS showed a small amount of starting material remained but a new major peak (Rt = 0.975 min, MS+1 = 379.0) was formed. The reaction mixture was diluted with H20 (1.20 L) and extracted with EtOAc 600 mL (300 mL x 2). The combined organic layers were washed with brine 600 mL (300 mL x 2), dried over Na2S04, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (Si02, Petroleum ether/Ethyl acetate = 10/1 to 2: 1). Methyl 2-(4-((tert-butoxycarbonyl)amino)phenyl)quinoline-3- carboxylate (30.0 g, 77.6 mmol, 68.8% yield) was obtained as a yellow solid which was confirmed by LCMS Rt = 0.973 min, MS+1 = 379.1

Reference： [1]Current Patent Assignee: INFLARX GMBH - WO2020/182384, 2020, A1 Location in patent: Page/Page column 32

84
[ 625-38-7 ]
[ 380430-49-9 ]
[ 105300-90-1 ]

Yield	Reaction Conditions	Operation in experiment
99%	With propan-1-ol; bis(1,5-cyclooctadiene)nickel ⁽⁰⁾; potassium <i>tert</i>-butylate; 4,4-dibenzyl-2-(pyridin-2-yl)-4,5-dihydrooxazole at 60℃; Sealed tube; regioselective reaction;

Reference： [1]Deng, Ruohan; Engle, Keary M.; Fu, Yue; Gao, Yang; Li, Zi-Qi; Liu, Peng; Tran, Van T. [Angewandte Chemie - International Edition, 2020, vol. 59, # 51, p. 23306 - 23312][Angew. Chem., 2020, vol. 132, # 51, p. 23506 - 23512,7]

85
[ 170235-26-4 ]
[ 380430-49-9 ]
C₁₆H₁₈N₂O₄S [ No CAS ]

Reference： [1]Nature Communications,2022,vol. 13

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
{[ item.p_purity ]}	{[ item.pr_size ]}	{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]}	{[ getRatePrice(item.pr_usd, 1,1) ]}	Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]}	{[ item.pr_usastock ]}	Inquiry -	{[ item.pr_chinastock ]}	Inquiry -

CAS No. :	380430-49-9	MDL No. :	MFCD02093054
Formula :	C₁₁H₁₆BNO₄	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	UBVOLHQIEQVXGM-UHFFFAOYSA-N
M.W :	237.06	Pubchem ID :	3613184
Synonyms :

Num. heavy atoms :	17
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.36
Num. rotatable bonds :	5
Num. H-bond acceptors :	4.0
Num. H-bond donors :	3.0
Molar Refractivity :	66.51
TPSA :	78.79 Å²

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) :	-6.76 cm/s

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	1.39
Log Po/w (WLOGP) :	0.52
Log Po/w (MLOGP) :	0.69
Log Po/w (SILICOS-IT) :	-0.86
Consensus Log Po/w :	0.35

[ CAS No. 380430-49-9 ] {[proInfo.proName]}

Quality Control of [ 380430-49-9 ]

Related Doc. of [ 380430-49-9 ]

Product Details of [ 380430-49-9 ]

Calculated chemistry of [ 380430-49-9 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 380430-49-9 ]

Application In Synthesis of [ 380430-49-9 ]

[ 380430-49-9 ] Synthesis Path-Upstream 1~5

[ 380430-49-9 ] Synthesis Path-Downstream 1~85

Related Functional Groups of
[ 380430-49-9 ]

Organoboron

Aryls

Amides

Amines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

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

Log S (ESOL) :	-2.12
Solubility :	1.81 mg/ml ; 0.00764 mol/l
Class :	Soluble
Log S (Ali) :	-2.65
Solubility :	0.533 mg/ml ; 0.00225 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.25
Solubility :	1.34 mg/ml ; 0.00566 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.36

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

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

[ CAS No. 380430-49-9 ] {[proInfo.proName]}

Quality Control of [ 380430-49-9 ]

Related Doc. of [ 380430-49-9 ]

Product Details of [ 380430-49-9 ]

Calculated chemistry of [ 380430-49-9 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 380430-49-9 ]

Application In Synthesis of [ 380430-49-9 ]

[ 380430-49-9 ] Synthesis Path-Upstream 1~5

[ 380430-49-9 ] Synthesis Path-Downstream 1~85

Related Functional Groups of [ 380430-49-9 ]

Organoboron

Aryls

Amides

Amines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 380430-49-9 ]