[ CAS No. 262433-02-3 ]

Name: 262433-02-3|tert-Butyl (2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamate|98%
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Product Details of [ 262433-02-3 ]

CAS No. :	262433-02-3	MDL No. :	MFCD08458201
Formula :	C₁₈H₂₈BNO₅	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	HTNAUNFQAMHASO-UHFFFAOYSA-N
M.W :	349.23 g/mol	Pubchem ID :	17750221
Synonyms :

Safety of [ 262433-02-3 ]

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

Application In Synthesis of [ 262433-02-3 ]

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

Upstream synthesis route of [ 262433-02-3 ]
Downstream synthetic route of [ 262433-02-3 ]

[ 262433-02-3 ] Synthesis Path-Upstream 1~1

1
[ 262433-02-3 ]
[ 461699-81-0 ]

Yield	Reaction Conditions	Operation in experiment
68%	With trifluoroacetic acid In dichloromethane at 5 - 20℃; for 2 h;	A mixture of Example 175C (45.0 g, 0.129 mole) in dichloromethane (270 mL) was cooled to <5 C. in an ice bath and treated with a 1:1 solution of TFA/dichloromethane (500 mL) while maintaining the reaction temperature below 5 C. The reaction was warmed to ambient temperature and stirred for 2 hours. The solvents were removed by evaporation at a pressure of 30 Torr and a bath temperature of <30 C. The residue was dissolved in dichloromethane (250 mL) and carefully washed with 2.5N sodium hydroxide (300 mL). The organic layer was extracted with brine (100 mL), dried (MgSO4), filtered, and concentrated to provide the desired product (21.7 g, 68percent). 1H NMR (DMSO-d6, 400 MHz) ? 7.05 (d, 1H), 6.98 (d, 1H), 6.59 (d, 1H), 5.13 (s, 2H), 3.75 (s, 3H), 1.25 (s, 12H); reverse phase HPLC (Hypersil HS, 5 ?m, 100 ?, 4.6?250 mm; 25percent-100percent acetonitrile/0.05M ammonium acetate over 10 minutes, 1 mL/min) Rt 11.03 min.
68%	Stage #1: With trifluoroacetic acid In dichloromethane at 5 - 20℃; for 2 h; Stage #2: With sodium hydroxide In dichloromethane; water	[0590] A mixture of Example 175C (45.0 g, 0.129 mole) in dichloromethane (270 mL) was cooled to <5° C. in an ice bath and treated with a 1:1 solution of TFA/dichloromethane (500 mL) while maintaining the reaction temperature below 5° C. The reaction was warmed to ambient temperature and stirred for 2 hours. The solvents were removed by evaporation at a pressure of 30 Torr and a bath temperature of <30° C. The residue was dissolved in dichloromethane (250 mL) and carefully washed with 2.5N sodium hydroxide (300 mL). The organic layer was extracted with brine (100 mL), dried (MgSO4), filtered, and concentrated to provide the desired product (21.7 g, 68percent). 1H NMR (DMSO-d6, 400 MHz) δ 7.05 (d, 1H), 6.98 (d, 1H), 6.59 (d, 1H), 5.13 (s, 2H), 3.75 (s, 3H), 1.25 (s, 12H); reverse phase HPLC (Hypersil HS, 5 μm, 100 A, 4.6.x.250 mm; 25percent-100percent acetonitrile/0.05M ammonium acetate over 10 minutes, 1 mL/min) Rt 11.03 min.
67.5%	With trifluoroacetic acid In dichloromethane	A. 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline A mixture of tert-butyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (45.0 g,.129 mol) was dissolved in dichloromethane (270 mL) then the solution was cooled to 5° C. in and ice bath. A mixture of 20percent trifluoroacetic acid in dichloromethane was added dropwise over the course of one hour while maintaining the temperature of the mixture at <5° C. The reaction mixture was warmed to ambient temperature and stirred for 2 hours. The solvents were removed under reduced pressure then the resulting oil was dissolved in dichloromethane (250 mL) and cautiously extracted with 2.5 N aqueous sodium hydroxide (300 mL) then brine (100 mL). The organic solution was dried over magnesium sulfate, filtered and the fitrate concentrated under reduced pressure to give 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (21.7 g, 67.5percent) as a light brown solid bismaleate: ¹H NMR (DMSO-d₆, 400 MHz) δ 7.06 (d, 1H), 6.98 (s, 1H), 8.09 (d, 1H), 6.59 (d, 1H), 5.13 (bs, 2H), 3.76 (s, 3H), 1.26 (s, 12H); RP-HPLC (Hypersil HS C18Hypersil HS C18, 5 μm, 100 A, 250*4.6 mm; 25percent-100percent acetonitrile-0.05 M ammonium acetate over 10 min, 1 mL/min) t_r 10.85 min.

67.5%

With trifluoroacetic acid In dichloromethane

A.
2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline
A mixture of tert-butyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (45.0 g, 0.129 mol) was dissolved in dichloromethane (270 mL) then the solution was cooled to 5° C. in and ice bath.
A mixture of 20percent trifluoroacetic acid in dichloromethane was added dropwise over the course of one hour while maintaining the temperature of the mixture at <5° C.
The reaction mixture was warmed to ambient temperature and stirred for 2 hours.
The solvents were removed under reduced pressure then the resulting oil was dissolved in dichloromethane (250 mL) and cautiously extracted with 2.5 N aqueous sodium hydroxide (300 mL) then brine (100 mL).
The organic solution was dried over magnesium sulfate, filtered and the fitrate concentrated under reduced pressure to give 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (21.7 g, 67.5percent) as a light brown solid bismaleate: ¹H NMR (DMSO-d₆, 400 MHz) δ 7.06 (d, 1H), 6.98 (s, 1H), 8.09 (d, 1H), 6.59 (d, 1H), 5.13 (bs, 2H), 3.76 (s, 3H), 1.26 (s, 12H); RP-HPLC (Hypersil HS C18 Hypersil HS C18, 5 μm, 100 A, 250*4.6 mm; 25percent-100percent acetonitrile-0.05 M ammonium acetate over 10 min, 1 mL/min) t_r 10.85 min.

Reference： [1] Patent: US2005/20619, 2005, A1, . Location in patent: Page 40-41
[2] Patent: US2005/43347, 2005, A1, . Location in patent: Page/Page column 49
[3] Patent: US2002/156081, 2002, A1,
[4] Patent: US6921763, 2005, B2,

[ 262433-02-3 ] Synthesis Path-Downstream 1~38

1
[ 262433-02-3 ]
[ 330792-74-0 ]
[ 330793-47-0 ]

Yield	Reaction Conditions	Operation in experiment
77%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate In 1,2-dimethoxyethane; water at 80℃;

Reference： [1]Burchat, Andrew F; Calderwood, David J; Friedman, Michael M; Hirst, Gavin C; Li, Biqin; Rafferty, Paul; Ritter, Kurt; Skinner, Barbara S [Bioorganic and medicinal chemistry letters, 2002, vol. 12, # 12, p. 1687 - 1690]

2
[ 330794-31-5 ]
[ 262433-02-3 ]
C₂₂H₂₈N₆O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; ethanol; water; at 80℃;	Synthesis of 1-(3-(4-amino-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)phenyl)ethanone (BA81, BA81d & BA81dd); A solution of tert-butyl 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylcarbamate (200 mg, 0.76 mmol) in EtOH (3.3 ml) was added to a solution of <strong>[330794-31-5]1-cyclopentyl-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine</strong> (BA80, 100 mg, 0.30 mmol) in DME (12 ml). Pd(PPh3)4 (30 mg, 0.03 mmol) and saturated Na2CO3 (1.9 ml) were added and the reaction was heated to 80 C. under an argon atmosphere overnight. After cooling, the reaction was extracted with saturated NaCl and CH2Cl2. Organic phases were combined, concentrated in vacuo and purified using silica gel column chromatography [MeOH-CH2Cl2, 5:95] yielding BA81. BA81 was dissolved in 50:50 CH2Cl2:TFA and stirred for one hour at room temperature. The reaction mixture was concentrated in vacuo and purified using by RP-HPLC (MeCN:H2O:0.1% TFA) to yield BA81d. BA81d was dissolved in CH2Cl2 (2 ml) and BBr3 (4 mL, 4 mol) was added slowly with a syringe, while stirring. The reaction was stirred at room temperature for 2 hours then concentrated in vacuo and purified using by RP-HPLC (MeCN:H2O:0.1% TFA) to yield BA81dd.

Reference： [1]Patent: US2007/293516,2007,A1 .Location in patent: Page/Page column 21

3
[ 73183-34-3 ]
[ 262433-01-2 ]
[ 262433-02-3 ]

Yield	Reaction Conditions	Operation in experiment
83%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium acetate In N,N-dimethyl-formamide at 80℃; Inert atmosphere;	20.3 (3) Preparation of tert-butyl (2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)amino carboxylate (0679) Tert-butyl (4-bromo-2-methoxyphenyl)amino carboxylate (5.0 g, 16.56 mmol), bis(pinacolato)diboron (5.05 g, 19.88 mmol) and potassium acetate (4.88 g, 49.80 mmol) were added to N,N-dimethylformamide (100 mL). Under the protection of nitrogen gas, [1,1′-bis(diphenyphosphino)ferrocene]dichloropalladium ( II) dichloromethane complex (410 mg, 0.50 mmol) was added. The mixture was heated to 80° C. and reacted overnight. After cooling to room temperature, water and dichloromethane were added, and the water phase and the organic phase were separated. The organic phase was washed with saturated saline solution for 3 times, dried with anhydrous sodium sulfate, and concentrated. The crude product was purified by silica gel column chromatography (petroleum ether:ethyl acetate=100:1) to get the title compound (4.8 g, yield: 83.0%).
65%	With potassium acetate; triethylamine In n-heptane; dichloromethane; N,N-dimethyl-formamide	1.b N1-[4-(4-Amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methoxyphenyl]-4-cyano-1-benzenesulfonamide b) tert-Butyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-carbamate. A mixture of tert-butyl N-(4-bromo-2-methoxyphenyl)carbamate (80% pure) (6.25 g, 16.56 mmol), diboron pinacol ester (5.05 g, 19.88 mmol), [1,1'-bis(diphenylphosphino) ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (0.41 g, 0.50 mmol) and potassium acetate (4.88 g, 49.80 mmol) in N,N-dimethylformamide (100 ml) was heated at 80° C. under an atomospher of nitrogen overnight. The mixture was allowed to cool to ambient temperature and then most of the solvent was removed under reduced pressure. Dichloromethane (100 ml) was added to the residue and the resulting solids were removed by filtration through a pad of celite. The filtrate was concentrated to leave a dark oil which was purified by flash column chromatography on silica using dichloromethane/n-heptane (1:2) with 2.5% triethylamine as mobile phase to give tert-butyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate as white solids (65% pure, 4.25 g, 7.92 mmol): 1H NMR (DMSO-d6, 400 MHz) δ 7.93(s, 1H), 7.83 (d, 1H), 7.25 (d, 1H), 7.16 (s, 1H), 3.83 (s, 3H), 1.46 (s, 9H), 1.30(s, 12H); RP-HPLC (Hypersil C18, 5 μm, 200 A, 25 cm; 50%-100% acetonitrile-0.1M ammonium acetate over 25 min, 1 ml/min) Rt 18.28 min.
60.3%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium acetate In N,N-dimethyl-formamide at 80℃; for 16h; Inert atmosphere;	6.2 (2) (2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl)phenyl)carbamic acid tert-butyl ester preparation A solution of tert-butyl (4-bromo-2-methoxyphenyl) carbamate (2.5 g, 8.3 mmol)Boronic acid pinacol ester (2.32 g, 9.1 mmol)And potassium acetate (1.63 g, 16.6 mmol) were added to N, N-dimethylformamide (100 mL)(Diphenylphosphine) ferrocene palladium dichloride dichloromethane complex (410 mg, 0.50 mmol) was added under nitrogen atmosphere,The reaction was allowed to proceed for 16 hours at 80 ° C,The organic phase was washed three times with saturated brine, dried over anhydrous sodium sulfate and concentrated. The crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 100: 1) to give the title compound To give the title compound (1.75 g, yield 60.3%).

	With potassium acetate at 80℃; for 16h;	175.C EXAMPLE 175C; tert-butyl 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylcarbamate A mixture of Example 175B (61.3 g, 203 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2?-bi-1,3,2-dioxaborolane (51.6 g, 203 mmol), [1.1'-bis(diphenylphosphino)ferrocene]dichloropalladium (HI) complex with dichloromethane (1:1) (3.2 g, 3.9 mmol), and potassium acetate (59.7 g, 609 mmol) in DMF (1.0 L) was heated to 80 C. under an atmosphere of nitrogen for 16 hours, cooled to ambient temperature, and concentrated. Dichloromethane (500 mL) was added to the residue and the resulting solid was removed by filtration through a pad of diatomaceous earth (Celite). The pad was washed with dichloromethane (4?50 mL) and the combined filtrates were concentrated, applied to a 550 gram silica gel column, and quickly eluted with heptane/ethyl acetate (85:15) The fractions showing product [Rt with conditions described in Example 175A=14.33 minutes, Rf of product=0.33 TLC (85:15 heptane/ethyl acetate), Rf of tert-butyl N-(4-bromo-2-methoxyphenyl)carbamate=0.48]. This material was treated with heptane (300 mL) and stirred at ambient temperature for 30 minutes. The mixture was cooled to about 5 C. for 3 hours and the resulting precipitate was collected by filtration to provide 24.4 g of the desired product. The filtrate was evaporated and the residue was purified by flash chromatography on a 400 gram silica gel column with 9:1 heptane/ethyl acetate to give an additional 8.8 g of the desired product.
	With potassium acetate In n-heptane; dichloromethane; N,N-dimethyl-formamide	175.C tert-butyl 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylcarbamate EXAMPLE 175C tert-butyl 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylcarbamate A mixture of Example 175B (61.3 g, 203 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi-1,3,2-dioxaborolane (51.6 g, 203 mmol), [1.1'-bis(diphenylphosphino)ferrocene]dichloropalladium (II) complex with dichloromethane (1:1) (3.2 g, 3.9 mmol), and potassium acetate (59.7 g, 609 mmol) in DMF (1.0 L) was heated to 80° C. under an atmosphere of nitrogen for 16 hours, cooled to ambient temperature, and concentrated. Dichloromethane (500 mL) was added to the residue and the resulting solid was removed by filtration through a pad of diatomaceous earth (Celite). The pad was washed with dichloromethane (4*50 mL) and the combined filtrates were concentrated, applied to a 550 gram silica gel column, and quickly eluted with heptane/ethyl acetate (85:15) The fractions showing product [Rt with conditions described in Example 175A=14.33 minutes, Rf of product=0.33 TLC (85:15 heptane/ethyl acetate), Rf of tert-butyl N-(4-bromo-2-methoxyphenyl)carbamate=0.48]. This material was treated with heptane (300 mL) and stirred at ambient temperature for 30 minutes. The mixture was cooled to about 5° C. for 3 hours and the resulting precipitate was collected by filtration to provide 24.4 g of the desired product. The filtrate was evaporated and the residue was purified by flash chromatography on a 400 gram silica gel column with 9:1 heptane/ethyl acetate to give an additional 8.8 g of the desired product.
	With potassium acetate In N,N-dimethyl-formamide at 80℃; for 16h;	175.C tert-butyl 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylcarbamate EXAMPLE 175C tert-butyl 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylcarbamate A mixture of Example 175B (61.3 g, 203 mmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi-1,3,2-dioxaborolane (51.6 g, 203 mmol), [1.1'-bis(diphenylphosphino)ferrocene]dichloropalladium (II) complex with dichloromethane (1:1) (3.2 g, 3.9 mmol), and potassium acetate (59.7 g, 609 mmol) in DMF (1.0 L) was heated to 80° C. under an atmosphere of nitrogen for 16 hours, cooled to ambient temperature, and concentrated. Dichloromethane (500 mL) was added to the residue and the resulting solid was removed by filtration through a pad of diatomaceous earth (Celite). The pad was washed with dichloromethane (4*50 mL) and the combined filtrates were concentrated, applied to a 550 gram silica gel column, and quickly eluted with heptane/ethyl acetate (85:15) The fractions showing product [Rt with conditions described in Example 175A=14.33 minutes, Rf of product=0.33 TLC (85:15 heptane/ethyl acetate), Rf of tert-butyl N-(4-bromo-2-methoxyphenyl)carbamate=0.48]. This material was treated with heptane (300 mL) and stirred at ambient temperature for 30 minutes. The mixture was cooled to about 5° C. for 3 hours and the resulting precipitate was collected by filtration to provide 24.4 g of the desired product. The filtrate was evaporated and the residue was purified by flash chromatography on a 400 gram silica gel column with 9:1 heptane/ethyl acetate to give an additional 8.8 g of the desired product.

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - US2017/112833, 2017, A1 Location in patent: Paragraph 0678-0679
[2]Current Patent Assignee: ABBVIE INC - US2003/187001, 2003, A1
[3]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - CN105884695, 2016, A Location in patent: Paragraph 0360; 0361; 0362
[4]Current Patent Assignee: ABBVIE INC - US2005/20619, 2005, A1 Location in patent: Page 40
[5]Current Patent Assignee: ABBVIE INC - US2005/26944, 2005, A1
[6]Current Patent Assignee: ABBVIE INC - US2005/43347, 2005, A1 Location in patent: Page/Page column 49

4
[ 118618-61-4 ]
[ 262433-02-3 ]
[ 832696-35-2 ]

Yield	Reaction Conditions	Operation in experiment
94%	With N-ethyl-N,N-diisopropylamine In n-heptane; dichloromethane	175.E N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-methyl-1H-indole-3-carboxamide EXAMPLE 175E N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-methyl-1H-indole-3-carboxamide A mixture of Example 175D (19.75 g, 79.3 mmol) in dichloromethane (150 mL) was treated with N,N-diisopropylethylamine (12.3 g, 95.2 mmol), cooled to <5° C. with an ice bath, and treated slowly with a solution of 1-methyl-1H-indole-2-carbonyl chloride (87.3 mmol) in dichloromethane (300 mL) while maintaining the reaction temperature below 5° C. The mixture was warmed to ambient temperature, stirred for 12 hours, extracted twice with water (150 mL, 100 mL), once with brine (100 mL), dried (MgSO4), filtered, and concentrated. The material was purified by flash chromatography using 400 g of silica gel and 3:1 heptane/ethyl acetate to provide the desired product (30.3 g, 94%). 1H NMR (DMSO-d6, 400 MHz) δ 9.35 (s, 1H), 8.03 (d, 1H), 7.69 (d, 1H), 7.57 (d, 1H), 7.1-7.3 (m, 4H), 7.12 (t, 1H), 4.02 (s, 3H), 3.91 (s, 3H), 1.31 (s, 12H); RP-HPLC (Hypersil HS, 5 μm, 100 Å, 4.6*250 mm; 25%-100% acetonitrile/0.05M ammonium acetate over 10 min, 1 mL/min) Rt 14.65 min.
	With N-ethyl-N,N-diisopropylamine In dichloromethane at 5 - 20℃; for 12h;	175.E EXAMPLE 175; N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-methyl-1H-indole-3-carboxamide A mixture of Example 175D (19.75 g, 79.3 mmol) in dichloromethane (150 mL) was treated with N,N-diisopropylethylamine (12.3 g, 95.2 mmol), cooled to <5 C. with an ice bath, and treated slowly with a solution of 1-methyl-1H-indole-2-carbonyl chloride (87.3 mmol) in dichloromethane (300 mL) while maintaining the reaction temperature below 5 C. The mixture was warmed to ambient temperature, stiffed for 12 hours, extracted twice with water (150 mL, 100 mL), once with brine (100 mL), dried (MgSO4), filtered, and concentrated. The material was purified by flash chromatography using 400 g of silica gel and 3:1 heptane/ethyl acetate to provide the desired product (30.3 g, 94%). 1H NMR (DMSO-d6, 400 MHz) ? 9.35 (s, 1H), 8.03 (d, 1H), 7.69 (d, 1H), 7.57 (d, 1H), 7.1-7.3 (m, 4H), 7.12 (t, 1H), 4.02 (s, 3H), 3.91 (s, 3H), 1.31 (s, 12H); RP-HPLC (Hypersil HS, 5 ?m, 100 ?, 4.6?250 mm; 25%-100% acetonitrile/0.05M ammonium acetate over 10 min, 1 mL/min) Rt 14.65 min.

Reference： [1]Current Patent Assignee: ABBVIE INC - US2005/26944, 2005, A1
[2]Current Patent Assignee: ABBVIE INC - US2005/20619, 2005, A1 Location in patent: Page 41

5
[ 262433-02-3 ]
[ 461699-81-0 ]

Yield	Reaction Conditions	Operation in experiment
68%	With trifluoroacetic acid; In dichloromethane; at 5 - 20℃; for 2h;	A mixture of Example 175C (45.0 g, 0.129 mole) in dichloromethane (270 mL) was cooled to <5 C. in an ice bath and treated with a 1:1 solution of TFA/dichloromethane (500 mL) while maintaining the reaction temperature below 5 C. The reaction was warmed to ambient temperature and stirred for 2 hours. The solvents were removed by evaporation at a pressure of 30 Torr and a bath temperature of <30 C. The residue was dissolved in dichloromethane (250 mL) and carefully washed with 2.5N sodium hydroxide (300 mL). The organic layer was extracted with brine (100 mL), dried (MgSO4), filtered, and concentrated to provide the desired product (21.7 g, 68%). 1H NMR (DMSO-d6, 400 MHz) ? 7.05 (d, 1H), 6.98 (d, 1H), 6.59 (d, 1H), 5.13 (s, 2H), 3.75 (s, 3H), 1.25 (s, 12H); reverse phase HPLC (Hypersil HS, 5 ?m, 100 ?, 4.6?250 mm; 25%-100% acetonitrile/0.05M ammonium acetate over 10 minutes, 1 mL/min) Rt 11.03 min.
68%		[0590] A mixture of Example 175C (45.0 g, 0.129 mole) in dichloromethane (270 mL) was cooled to <5 C. in an ice bath and treated with a 1:1 solution of TFA/dichloromethane (500 mL) while maintaining the reaction temperature below 5 C. The reaction was warmed to ambient temperature and stirred for 2 hours. The solvents were removed by evaporation at a pressure of 30 Torr and a bath temperature of <30 C. The residue was dissolved in dichloromethane (250 mL) and carefully washed with 2.5N sodium hydroxide (300 mL). The organic layer was extracted with brine (100 mL), dried (MgSO4), filtered, and concentrated to provide the desired product (21.7 g, 68%). 1H NMR (DMSO-d6, 400 MHz) delta 7.05 (d, 1H), 6.98 (d, 1H), 6.59 (d, 1H), 5.13 (s, 2H), 3.75 (s, 3H), 1.25 (s, 12H); reverse phase HPLC (Hypersil HS, 5 mum, 100 A, 4.6×250 mm; 25%-100% acetonitrile/0.05M ammonium acetate over 10 minutes, 1 mL/min) Rt 11.03 min.
67.5%	With trifluoroacetic acid; In dichloromethane;	A. 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline A mixture of tert-butyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (45.0 g,.129 mol) was dissolved in dichloromethane (270 mL) then the solution was cooled to 5 C. in and ice bath. A mixture of 20% trifluoroacetic acid in dichloromethane was added dropwise over the course of one hour while maintaining the temperature of the mixture at <5 C. The reaction mixture was warmed to ambient temperature and stirred for 2 hours. The solvents were removed under reduced pressure then the resulting oil was dissolved in dichloromethane (250 mL) and cautiously extracted with 2.5 N aqueous sodium hydroxide (300 mL) then brine (100 mL). The organic solution was dried over magnesium sulfate, filtered and the fitrate concentrated under reduced pressure to give 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (21.7 g, 67.5%) as a light brown solid bismaleate: 1H NMR (DMSO-d6, 400 MHz) delta 7.06 (d, 1H), 6.98 (s, 1H), 8.09 (d, 1H), 6.59 (d, 1H), 5.13 (bs, 2H), 3.76 (s, 3H), 1.26 (s, 12H); RP-HPLC (Hypersil HS C18Hypersil HS C18, 5 mum, 100 A, 250*4.6 mm; 25%-100% acetonitrile-0.05 M ammonium acetate over 10 min, 1 mL/min) tr 10.85 min.

67.5%

With trifluoroacetic acid; In dichloromethane;

A. 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline A mixture of tert-butyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (45.0 g, 0.129 mol) was dissolved in dichloromethane (270 mL) then the solution was cooled to 5 C. in and ice bath. A mixture of 20% trifluoroacetic acid in dichloromethane was added dropwise over the course of one hour while maintaining the temperature of the mixture at <5 C. The reaction mixture was warmed to ambient temperature and stirred for 2 hours. The solvents were removed under reduced pressure then the resulting oil was dissolved in dichloromethane (250 mL) and cautiously extracted with 2.5 N aqueous sodium hydroxide (300 mL) then brine (100 mL). The organic solution was dried over magnesium sulfate, filtered and the fitrate concentrated under reduced pressure to give 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (21.7 g, 67.5%) as a light brown solid bismaleate: 1H NMR (DMSO-d6, 400 MHz) delta 7.06 (d, 1H), 6.98 (s, 1H), 8.09 (d, 1H), 6.59 (d, 1H), 5.13 (bs, 2H), 3.76 (s, 3H), 1.26 (s, 12H); RP-HPLC (Hypersil HS C18 Hypersil HS C18, 5 mum, 100 A, 250*4.6 mm; 25%-100% acetonitrile-0.05 M ammonium acetate over 10 min, 1 mL/min) tr 10.85 min.

Reference： [1]Patent: US2005/20619,2005,A1 .Location in patent: Page 40-41
[2]Patent: US2005/43347,2005,A1 .Location in patent: Page/Page column 49
[3]Patent: US2002/156081,2002,A1
[4]Patent: US6921763,2005,B2

6
[ 799293-85-9 ]
[ 262433-02-3 ]
tert-butyl 4-(4-aminothieno[3,2-c]pyridin-3-yl)-2-methoxyphenylcarbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 85℃; for 16h;	A solution of Example 1B (1.0 g, 4.365 mmol) in ethyleneglycol dimethyl ether (20 mL) was treated with tert-butyl 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylcarbamate (1.83 g, 5.238 mmol), Pd(PPh3)4 (0.303 g, 0.262 mmol), and a solution of sodium carbonate (1.11 g, 10.473 mmol) in water (10 mL), stirred at 85 C. for 16 hours under nitrogen, concentrated, and treated with dichloromethane. The organic layer was dried (MgSO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 100% ethyl acetate to provide 1.62 g (100%) of the desired product. 1H NMR (DMSO-d6, 400 MHz) ? 8.1 (s, 1H), 7.8 (m, 2H), 7.41 (s, 1H), 7.2 (m, 1H), 7.1 (s, 1H), 7-6.95 (m, 1H), 3.8 (s, 3H), 1.458 (s, 9H); LCMS (Thermoquest AQA single-quad MS, Genesis C18 column, 3 ?m particle size, 33?4.6 mm; 70% 50 mM ammonium acetate in water to 95% acetonitrile over 6 min, 0.8 to 0.5 ml/min) Rt=3.73 min (95%), MS m/e 372.2 (M+H)+.
100%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; dichloromethane; water; ethyl acetate; at 85℃; for 16h;	EXAMPLE 294A tert-butyl 4-(4-aminothieno[3,2-c]pyridin-3-yl)-2-methoxyphenylcarbamate A solution of Example 1B (1.0 g, 4.365 mmol) in ethyleneglycol dimethyl ether (20 mL) was treated with tert-butyl 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylcarbamate (1.83 g, 5.238 mmol), Pd(PPh3)4 (0.303 g, 0.262 mmol), and a solution of sodium carbonate (1.1 g, 10.473 mmol) in water (10 mL), stirred at 85 C. for 16 hours under nitrogen, concentrated, and treated with dichloromethane. The organic layer was dried (MgSO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 100% ethyl acetate to provide 1.62 g (100%) of the desired product. 1H NMR (DMSO-d6, 400 MHz) delta 8.1 (s, 1H), 7.8 (m, 2H), 7.41 (s, 1H), 7.2 (m, 1H), 7.1 (s, 1H), 7-6.95 (m, 1H), 3.8 (s, 3H), 1.458 (s, 9H); LCMS (Thermoquest AQA single-quad MS, Genesis C18 column, 3 mum particle size, 33*4.6 mm; 70% 50 mM ammonium acetate in water to 95% acetonitrile over 6 min, 0.8 to 0.5 mL/min) Rt=3.73 min (95%), MS m/e 372.2 (M+H)+.
1.62 g (100%)	With sodium carbonate;Pd(PPh3)4; In 1,2-dimethoxyethane; dichloromethane; water; ethyl acetate;	EXAMPLE 294A tert-butyl 4-(4-aminothieno[3,2-c]pyridin-3-yl)-2-methoxyphenylcarbamate A solution of Example 1B (1.0 g, 4.365 mmol) in ethyleneglycol dimethyl ether (20 mL) was treated with tert-butyl 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylcarbamate (1.83 g, 5.238 mmol), Pd(PPh3)4 (0.303 g, 0.262 mmol), and a solution of sodium carbonate (1.11 g, 10.473 mmol) in water (10 mL), stirred at 85 C. for 16 hours under nitrogen, concentrated, and treated with dichloromethane. The organic layer was dried (MgSO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 100% ethyl acetate to provide 1.62 g (100%) of the desired product. 1H NMR (DMSO-d6, 400 MHz) delta 8.1 (s, 1H), 7.8 (m, 2H), 7.41 (s, 1H), 7.2 (m, 1H), 7.1 (s, 1H), 7-6.95 (m, 1H), 3.8 (s, 3H), 1.458 (s, 9H); LCMS (Thermoquest AQA single-quad MS, Genesis C18 column, 3 mum particle size, 33*4.6 mm; 70% 50 mM ammonium acetate in water to 95% acetonitrile over 6 min, 0.8 to 0.5 mL/min) Rt=3.73 min (95%), MS m/e 372.2 (M+H)+.

Reference： [1]Patent: US2005/20619,2005,A1 .Location in patent: Page 56
[2]Patent: US2005/43347,2005,A1 .Location in patent: Page/Page column 65
[3]Patent: US2005/26944,2005,A1

7
[ 330794-06-4 ]
[ 262433-02-3 ]
tert-Butyl N-{4-[4-amino-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl} carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	With sodium carbonate In methanol; 1,2-dimethoxyethane; dichloromethane; water	b b b tert-Butyl N-{4-[4-amino-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}carbamate 3-Iodo-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (270 mg, 0.754 mmol), tert-butyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate(290 mg, 0.829 mmol), palladium tetrakistriphenyphosphine(52 mg, 0.045 mmol) and sodium carbonate (192 mg, 1.81 mmol) were mixed with ethylene glycol dimethyl ether (8 mL) and water (4 mL). The reaction mixture was heated at reflux overnight. Organic solvent was removed under reduced pressure and the aqueous layer was extracted with dichloromethane. The combined organic layer was washed with water then brine, dried over MgSO4, filtered and evaporated. The residue was purified by flash column chromatography using dichloromethane/methanol (90:10 to 70:30) as mobile phase to give tert-butyl N- {4-[4-amino-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}carbamate (250 mg, 73%). 1H NMR (DMSO-d6) δ 1.48 (s, 9H),1.88 (m, 2H), 2.10 (m, 2H), 2.24 (m, 5H), 2.92 (m, 2H), 3.69(s, 3H), 4.64 (m, 1H), 7.21 (m, 2H), 7.91 (d, J=8.16 Hz, 1H), 8.04 (s, 1H), 8.23 (s, 1H). LCMS (Thermoquest AQA single Quad MS, Finnigan HPLC-Column: Genesis, C18, 3 um, 33*4.6 mm. Eluents: 30% B/A to 95% B/A in 4.5 min. (B: acetonitrile, A: 50 mM ammonia acetate buffer, pH 4.5), 0.8 mL/min.): MH+=454.2, Rt=1.67 min.
73%	With sodium carbonate In methanol; 1,2-dimethoxyethane; dichloromethane; water	b b b tert-Butyl N- {4-[4-amino-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl} carbamate 3-Iodo-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (270 mg, 0.754 mmol), tert-butyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate(290 mg, 0.829 mmol), palladium tetrakistriphenyphosphine(52 mg, 0.045 mmol) and sodium carbonate (192 mg, 1.81 mmol) were mixed with ethylene glycol dimethyl ether (8 mL) and water (4 mL). The reaction mixture was heated at reflux overnight. Organic solvent was removed under reduced pressure and the aqueous layer was extracted with dichloromethane. The combined organic layer was washed with water then brine, dried over MgSO4, filtered and evaporated. The residue was purified by flash column chromatography using dichloromethane/methanol (90:10 to 70:30) as mobile phase to give tert-butyl N-{4-[4-amino-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}carbamate (250 mg, 73%). 1H NMR (DMSO-d6) δ 1.48 (s, 9H),1.88 (m, 2H), 2.10 (m, 2H), 2.24 (m, 5H), 2.92 (m, 2H), 3.69(s, 3H), 4.64 (m, 1H), 7.21 (m, 2H), 7.91 (d, J=8.16 Hz, 1H), 8.04 (s, 1H), 8.23 (s, 1H). LCMS (Thermoquest AQA single Quad MS, Finnigan HPLC-Column: Genesis, C18, 3 um, 33*4.6 mm. Eluents: 30% B/A to 95% B/A in 4.5 min. (B: acetonitrile, A: 50 mM ammonia acetate buffer, pH 4.5), 0.8 mL/min.): MH+=454.2, Rt=1.67 min.
73%	With sodium carbonate In methanol; 1,2-dimethoxyethane; dichloromethane; water	447.b b) b) tert-Butyl N-{4-[4-amino-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}carbamate 3-iodo-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (270 mg, 0.754 mmol), tert-butyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate(290 mg, 0.829 mmol), palladium tetrakistriphenyphosphine(52 mg, 0.045 mmol) and sodium carbonate (192 mg, 1.81 mmol) were mixed with ethylene glycol dimethyl ether (8 mL) and water (4 mL). The reaction mixture was heated at reflux overnight. Organic solvent was removed under reduced pressure and the aqueous layer was extracted with dichloromethane. The combined organic layer was washed with water then brine, dried over MgSO4, filtered and evaporated. The residue was purified by flash column chromatography using dichloromethane/methanol (90:10 to 70:30) as mobile phase to give tert-butyl N-{4-[4-amino-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}carbamate (250 mg, 73%). 1H NMR (DMSO-d6) δ 1.48 (s, 9H), 1.88 (m, 2H), 2.10 (m, 2H), 2.24 (m, 5H), 2.92 (m, 2H), 3.69(s, 3H), 4.64 (m, 1H), 7.21 (m, 2H), 7.91 (d, J=8.16 Hz, 1H), 8.04 (s, 1H), 8.23 (s, 1H). LCMS (Thermoquest AQA single Quad MS, Finnigan HPLC-Column: Genesis, C18, 3 um, 33*4.6 mm. Eluents: 30% B/A to 95% B/A in 4.5 min. (B: acetonitrile, A: 50 mM ammonia acetate buffer, pH 4.5), 0.8 mL/min.): MH+=454.2, Rt=1.67 min.

73%	With sodium carbonate In methanol; 1,2-dimethoxyethane; dichloromethane; water	462.b b) b) tert-Butyl N-{4-[4-amino-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}carbamate 3-iodo-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (270 mg, 0.754 mmol), tert-butyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate(290 mg, 0.829 mmol), palladium tetrakistriphenyphosphine(52 mg, 0.045 mmol) and sodium carbonate (192 mg, 1.81 mmol) were mixed with ethylene glycol dimethyl ether (8 mL) and water (4 mL). The reaction mixture was heated at reflux overnight. Organic solvent was removed under reduced pressure and the aqueous layer was extracted with dichloromethane. The combined organic layer was washed with water then brine, dried over MgSO4, filtered and evaporated. The residue was purified by flash column chromatography using dichloromethane/methanol (90:10 to 70:30) as mobile phase to give tert-butyl N-{4-[4-amino-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}carbamate (250 mg, 73%). 1H NMR (DMSO-d6) δ 1.48 (s, 9H),1.88 (m, 2H), 2.10 (m, 2H), 2.24 (m, 5H), 2.92 (m, 2H), 3.69(s, 3H), 4.64 (m, 1H), 7.21 (m, 2H), 7.91 (d, J=8.16 Hz, 1H), 8.04 (s, 1H), 8.23 (s, 1H). LCMS (Thermoquest AQA single Quad MS, Finnigan HPLC-Column: Genesis, C18, 3 um, 33*4.6 mm. Eluents: 30% B/A to 95% B/A in 4.5 min. (B: acetonitrile, A: 50 mM ammonia acetate buffer, pH 4.5), 0.8 mL/min.): MH+=454.2, Rt=1.67 min.
73%	With sodium carbonate In methanol; 1,2-dimethoxyethane; dichloromethane; water	B B. B. tert-Butyl N-{4-[4-amino-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}carbamate 3-Iodo-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (270 mg, 0.754 mmol), tert-butyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (290 mg, 0.829 mmol), palladium tetrakistriphenyphosphine (52 mg, 0.045 mmol) and sodium carbonate (192 mg, 1.81 mmol) were mixed in ethylene glycol dimethyl ether (8 mL) and water (4 mL). The reaction mixture was heated at reflux overnight under nitrogen. Organic solvent was removed under reduced pressure and the aqueous layer was extracted with dichloromethane. The combined organic layer was washed with water then brine, dried over MgSO4, filtered and evaporated. The residue was purified by flash column chromatography using dichloromethane/methanol (90:10 to 70:30) as mobile phase to give tert-butyl N-{4-[4-amino-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}carbamate (250 mg, 73%). 1H NMR (DMSO-d6) δ 1.48 (s, 9H), 1.88 (m, 2H), 2.10 (m, 2H), 2.24 (m, 5H), 2.92 (m, 2H), 3.69 (s, 3H), 4.64 (m, 1H), 7.21 (m, 2H), 7.91 (d, J=8.16 Hz, 1H), 8.04 (s, 1H), 8.23 (s, 1H). LCMS (Thermoquest AQA single Quad MS, Finnigan HPLC-Column: Genesis, C18, 3 um, 33*4.6 mm. Eluents: 30% B/A to 95% B/A in 4.5 min. (B: acetonitrile, A: 50 mM ammonia acetate buffer, pH 4.5), 0.8 mL/min.): MH+=454.2, Rt=1.67 min.
73%	With sodium carbonate In 1,2-dimethoxyethane; water Heating / reflux;	234.B [1300] 3-Iodo-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (270 mg, 0.754 mmol), tert-butyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (290 mg, 0.829 mmol), palladium tetrakistriphenyphosphine (52 mg, 0.045 mmol) and sodium carbonate (192 mg, 1.81 mmol) were mixed in ethylene glycol dimethyl ether (8 mL) and water (4 mL). The reaction mixture was heated at reflux overnight under nitrogen. Organic solvent was removed under reduced pressure and the aqueous layer was extracted with dichloromethane. The combined organic layer was washed with water then brine, dried over MgSO4, filtered and evaporated. The residue was purified by flash column chromatography using dichloromethane/methanol (90:10 to 70:30) as mobile phase to give tert-butyl N-{4-[4-amino-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}carbamate (250 mg, 73%). 1H NMR (DMSO-d6) δ 1.48 (s, 9H), 1.88 (m, 2H), 2.10 (m, 2H), 2.24 (m, 5H), 2.92 (m, 2H), 3.69 (s, 3H), 4.64 (m, 1H), 7.21 (m, 2H), 7.91 (d, J=8.16 Hz, 1H), 8.04 (s, 1H), 8.23 (s, 1H). LCMS (Thermoquest AQA single Quad MS, Finnigan HPLC-Column: Genesis, C18, 3 um, 33×4.6 mm. Eluents: 30% B/A to 95% B/A in 4.5 min. (B: acetonitrile, A: 50 mM ammonia acetate buffer, pH 4.5), 0.8 mL/min.): MH+=454.2, Rt=1.67 min.
	With sodium carbonate In methanol; 1,2-dimethoxyethane; dichloromethane; water	B B. B. tert-Butyl N- {4-[4-amino-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}carbamate 3-Iodo-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (270 mg, 0.754 mmol), tert-butyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (290 mg, 0.829 mmol), palladium tetrakistriphenyphosphine (52 mg, 0.045 mmol) and sodium carbonate (192 mg, 1.81 mmol) were mixed in ethylene glycol dimethyl ether (8 mL) and water (4 mL). The reaction mixture was heated at reflux overnight under nitrogen. Organic solvent was removed under reduced pressure and the aqueous layer was extracted with dichloromethane. The combined organic layer was washed with water then brine, dried over MgSO4, filtered and evaporated. The residue was purified by flash column chromatography using dichloromethane/methanol (90:10 to 70:30) as mobile phase to give tert-butyl N- {4-[4-amino-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}carbamate (250 mg, 73°/). 1H NMR (DMSO-d6) δ 1.48 (s, 9H), 1.88 (m, 2H), 2.10 (m, 2H), 2.24 (m, 5H), 2.92 (m, 2H), 3.69 (s, 3H), 4.64 (m, 1H), 7.21 (m, 2H), 7.91 (d, J=8.16 Hz, 1H), 8.04 (s, 1H), 8.23 (s, 1H). LCMS (Thermoquest AQA single Quad MS, Finnigan HPLC-Column: Genesis, C18, 3 um, 33*4.6 mm. Eluents: 30% B/A to 95% B/A in 4.5 min. (B: acetonitrile, A: 50 mM ammonia acetate buffer, pH 4.5), 0.8 mL/min.): MH+=454.2, Rt=1.67 min.

Reference： [1]Current Patent Assignee: ABBVIE INC - US2002/156081, 2002, A1
[2]Current Patent Assignee: ABBVIE INC - US2002/156081, 2002, A1
[3]Current Patent Assignee: ABBVIE INC - US6921763, 2005, B2
[4]Current Patent Assignee: ABBVIE INC - US6921763, 2005, B2
[5]Current Patent Assignee: ABBVIE INC - US6921763, 2005, B2
[6]Current Patent Assignee: ABBVIE INC - US2004/6083, 2004, A1 Location in patent: Page/Page column 104
[7]Current Patent Assignee: ABBVIE INC - US2002/156081, 2002, A1

8
ammonium acetate [ No CAS ]
[ 330793-99-2 ]
[ 262433-02-3 ]
tert-butyl N-(4-{4-amino-1-[4-nitrophenyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate In <i>N</i>-methyl-acetamide; water; acetonitrile	tert-butyl N-(4-{4-amino-1-[4-nitrophenyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)carbamate 4-amino-1-[4-nitrophenyl]-3-iodo-1H-pyrazolo[3,4-d]pyrimidine 1H NMR (DMSO-d6, 400 MHz) δ 8.4952-8.4720 (m, 2H), 8.4142-8.3654 (m, 3H); LCMS (Perkin Elmer, Pecosphere C18 column, 3 um particle size, 334.6 mm; 100% 50 mM ammonium Acetate in Water to 100% Acetonitrile over 5 min, 3.0 to 3.5 mil/min) tR=3.73 min (100%) M+380.6. tert-butyl N-(4-{4-amino-1-[4-nitrophenyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)carbamate A suspension of 4-amino-1-[4-nitrophenyl]-3-iodo-1H-pyrazolo[3,4-d]pyrimidine (0.500 g, 1.31 mmol) in dimethylformamide (8 mL) was treated with tert-butyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (0.915 g, 2.62 mmol), tetrakis(triphenylphosphine)palladium (0.091 g, 0.06 mmol), and a solution of sodium carbonate (0.333 g, 3.14 mmol) in water (4 mL). The reaction mixture stirred at 85° C. for 26 h under a nitrogen atmosphere. Water was added to the reaction mixture. The precipitate was filtered and washed with water. The solid was triturated with diethyl ether to give 0.431 g, (63%) of tert-butyl N-(4-{4-amino-1-[4-nitrophenyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)carbamate. 1H NMR (DMSO-d6, 400 MHz) δ 8.6862-8.6634 (d, 2H, J=9.12 Hz), 8.4897-8.4423 (m, 3H), 8.1117 (s, 1H), 8.0074-7.9872 (d, 1H, J=8.08 Hz), 7.3743-7.3293 (m, 2H), 3.9189 (s, 3H), 1.4959 (s, 9H); LCMS (Perkin Elmer, Pecosphere C18 column, 3um particle size, 334.6 mm; 100% 50 mM ammonium Acetate in Water to 100% Acetonitrile over 5 min, 3.0 to 3.5 mil/min) tR=4.38 min M+ 478.1.

Reference： [1]Current Patent Assignee: ABBVIE INC - US2002/156081, 2002, A1

9
[ 461699-32-1 ]
[ 262433-02-3 ]
trans-tert-butyl N-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%	With sodium carbonate In methanol; 1,2-dimethoxyethane; dichloromethane; water	206.a a a trans-tert-butyl N-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)carbamate trans-3-Iodo-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (4.0 g, 9.06 mmol), tert-butyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (3.48 g, 9.97 mmol), palladium tetrakistriphenyphosphine (0.63 g, 0.64 mmol) and sodium carbonate (2.30 g, 21.75 mmol) were mixed with ethylene glycol dimethyl ether (100 mL) and water (50 mL). The reaction mixture was heated at reflux overnight. Organic solvent was removed under reduced pressure and the aqueous layer was extracted with dichloromethane. The combined organic layer was washed with water then brine, dried over MgSO4, filtered and evaporated. The residue was purified by flash column chromatography using dichloromethane/methanol (80:20) as mobile phase to give trans-tert-butyl N-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)carbamate (4.75 g, 98%). 1H NMR (DMSO-d6) δ 1.48 (m, 11H), 2.02 (m, 6H), 2.15 (s, 3H), 2.35 (m, 5H), 2.53 (m, 4H), 3.87 (s, 3H), 4.64 (m, 1H), 7.20 (m, 2H), 7.90 (d, J=8.15, 1H), 8.03 (s, 1H), 8.22 (s, 1H).
98%	With sodium carbonate In methanol; 1,2-dimethoxyethane; dichloromethane; water	206.a a) a) trans-tert-butyl N-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)carbamate trans-3-Iodo-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (4.0 g, 9.06 mmol), tert-butyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (3.48 g, 9.97 mmol), palladium tetrakistriphenyphosphine (0.63 g, 0.64 mmol) and sodium carbonate (2.30 g, 21.75 mmol) were mixed with ethylene glycol dimethyl ether (100 mL) and water (50 mL). The reaction mixture was heated at reflux overnight. Organic solvent was removed under reduced pressure and the aqueous layer was extracted with dichloromethane. The combined organic layer was washed with water then brine, dried over MgSO4, filtered and evaporated. The residue was purified by flash column chromatography using dichloromethane/methanol (80:20) as mobile phase to give trans-tert-butyl N-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)carbamate (4.75 g, 98%). 1H NMR (DMSO-d6) δ 1.48 (m, 11H), 2.02 (m, 6H), 2.15 (s, 3H), 2.35 (m, 5H), 2.53 (m, 4H), 3.87 (s, 3H), 4.64 (m, 1H), 7.20 (m, 2H), 7.90 (d, J=8.15, 1H), 8.03 (s, 1H), 8.22 (s, 1H).
89%	With sodium carbonate In methanol; 1,2-dimethoxyethane; dichloromethane; water	398.a a) a) cis-tert-Butyl N-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)carbamate cis-3-iodo-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (10 g, 22.66 mmol), tert-butyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (9.49 g, 27.17 mmol), palladium tetrakistriphenyphosphine (1.57 g, 1.36 mmol) and sodium carbonate (5.76 g, 54.38 mmol) were mixed with ethylene glycol dimethyl ether (180 mL) and water (90 mL). The reaction mixture was heated at reflux overnight. Organic solvent was removed under reduced pressure and the aqueous layer was extracted with dichloromethane. The combined organic layer was washed with water then brine, dried over MgSO4, filtered and evaporated. The residue was purified by preparative thin layer column chromatography using dichloromethane/methanol (80:20) as mobile phase to give cis-tert-butyl N-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)carbamate (10.859 g, 89%). 1H NMR (DMSO-d6) δ 1.49 (s, 9H), 1.58 (m, 2H), 1.71 (m, 2H), 2.08 (m, 2H), 2.17 (s, 3H), 2.45 (m, 4H), 2.38 (m, 4H), 2.45 (m, 3H), 3.87 (s, 3H), 4.80 (m, 1H), 7.22 (m, 2H), 7.91 (d, J=8.14, 1H), 8.04 (s, 1H), 8.22 (s, 1H).

Reference： [1]Current Patent Assignee: ABBVIE INC - US2002/156081, 2002, A1
[2]Current Patent Assignee: ABBVIE INC - US6921763, 2005, B2
[3]Current Patent Assignee: ABBVIE INC - US6921763, 2005, B2

10
[ 262433-02-3 ]
trans-tert-butyl N-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With sodium carbonate In methanol; 1,2-dimethoxyethane; dichloromethane; water	a a a cis-tert-Butyl N-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)carbamate cis-3-Iodo-1-[4-(4-methylpiperazino)cyclohexyl]1H-pyrazolo[3,4-d]pyrimidin-4-amine (IO g, 22.66 mmol), tert-butyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (9.49 g, 27.17 mmol), palladium tetrakistriphenyphosphine (1.57 g, 1.36 mmol) and sodium carbonate (5.76 g, 54.38 mmol) were mixed with ethylene glycol dimethyl ether (180 mL) and water (90 mL). The reaction mixture was heated at reflux overnight. Organic solvent was removed under reduced pressure and the aqueous layer was extracted with dichloromethane. The combined organic layer was washed with water then brine, dried over MgSO4, filtered and evaporated. The residue was purified by preparative thin layer column chromatography using dichloromethane/methanol (80:20) as mobile phase to give cis-tert-butyl N-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)carbamate (10.859 g, 89%). 1H NMR (DMSO-d6) 6 1.49 (s, 9H), 1.58 (m, 2H), 1.71 (m, 2H), 2.08 (m, 2H), 2.17 (s, 3H), 2.45 (m, 4H), 2.38 (m, 4H), 2.45 (m, 3H), 3.87 (s, 3H), 4.80 (m, 1H), 7.22 (m, 2H), 7.91 (d, J=8.14, 1H), 8.04 (s, 1H), 8.22 (s, 1H).

Reference： [1]Current Patent Assignee: ABBVIE INC - US2002/156081, 2002, A1

11
3-iodo-1-(1'-methyl[1,4'-bipiperidin]-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine [ No CAS ]
[ 262433-02-3 ]
tert-Butyl N-{4-[4-amino-1-[1-(1-methylpiperidin-4-yl)-piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl} carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%	With ammonium hydroxide; sodium carbonate In methanol; 1,2-dimethoxyethane; dichloromethane; water	210.e e e tert-Butyl N- {4-[4-amino-1-[1-(1-methylpiperidin-4-yl)-piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl} carbamate 3-Iodo-1-[1-(1-methylpiperidin-4-yl)]-piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (2.39 g, 5.41 mmol), tert-butyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (2.08 g, 5.96 mmol), palladium tetrakistriphenyphosphine (0.375 g, 0.32 mmol) and sodium carbonate (1.38 g, 13.00 mmol) were mixed with ethylene glycol dimethyl ether (80 mL) and water (40 mL). The reaction mixture was heated at reflux overnight. Organic solvent was removed under reduced pressure and the aqueous layer was extracted with dichloromethane. The combined organic layer was washed with water then brine, dried over MgSO4, filtered and evaporated. The residue was purified by flash column chromatography using dichloromethane/methanol/ammonium hydroxide (95:5:0.5) as mobile phase to give tert-butyl N-{4-[4-amino-1-[1-(1-methylpiperidin-4-yl)-piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}carbamate (1.67 g, 57%). 1H NMR (DMSO-d6) δ 1.48 (m, 11H), 1.71 (m, 2H) 1.86 (m, 4H), 2.14 (s, 3H), 2.18 (m, 3H), 2.32 (m, 2H), 2.80 (m, 2H), 3.89 (s, 3H), 4.64 (m, 1H), 7.22 (m, 2H), 7.91 (d, J=8.12, 1H), 8.03 (s, 1H), 8.21 (s, 1H).
57%	With ammonium hydroxide; sodium carbonate In methanol; 1,2-dimethoxyethane; dichloromethane; water	e e e tert-Butyl N-{4-[4-amino-1-[1-(1-methylpiperidin-4-yl)-piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl} carbamate 3-Iodo-1-[1-(1-methylpiperidin-4-yl)]-piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (2.39 g, 5.41 mmol), tert-butyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (2.08 g, 5.96 mmol), palladium tetrakistriphenyphosphine (0.375 g, 0.32 mmol) and sodium carbonate (1.38 g, 13.00 mmol) were mixed with ethylene glycol dimethyl ether (80 mL) and water (40 mL). The reaction mixture was heated at reflux overnight. Organic solvent was removed under reduced pressure and the aqueous layer was extracted with dichloromethane. The combined organic layer was washed with water then brine, dried over MgSO4, filtered and evaporated. The residue was purified by flash column chromatography using dichloromethane/methanol/ammonium hydroxide (95:5:0.5) as mobile phase to give tert-butyl N- {4-[4-amino-1-[1-(1-methylpiperidin-4-yl)-piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}carbamate (1.67 g, 57%). 1H NMR (DMSO-d6) δ 1.48 (m, 1H), 1.71 (m, 2H) 1.86 (m, 4H), 2.14 (s, 3H), 2.18 (m, 3H), 2.32 (m, 2H), 2.80 (m, 2H), 3.89 (s, 3H), 4.64 (m, 1H), 7.22 (m, 2H), 7.91 (d, J=8.12, 1H), 8.03 (s, 1H), 8.21 (s, 1H).
57%	With ammonium hydroxide; sodium carbonate In methanol; 1,2-dimethoxyethane; dichloromethane; water	210.e e) e) tert-Butyl N-{4-[4-amino-1-[1-(1-methylpiperidin-4-yl)-piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}carbamate 3-Iodo-1-[1-(1-methylpiperidin-4-yl)]-piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (2.39 g, 5.41 mmol), tert-butyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (2.08 g, 5.96 mmol), palladium tetrakistriphenyphosphine (0.375 g, 0.32 mmol) and sodium carbonate (1.38 g, 13.00 mmol) were mixed with ethylene glycol dimethyl ether (80 mL) and water (40 mL). The reaction mixture was heated at reflux overnight. Organic solvent was removed under reduced pressure and the aqueous layer was extracted with dichloromethane. The combined organic layer was washed with water then brine, dried over MgSO4, filtered and evaporated. The residue was purified by flash column chromatography using dichloromethane/methanol/ammonium hydroxide (95:5:0.5) as mobile phase to give tert-butyl N-{4-[4-amino-1-[1-(1-methylpiperidin-4-yl)-piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}carbamate (1.67 g, 57%). 1H NMR (DMSO-d6) δ 1.48 (m, 11H), 1.71 (m, 2H) 1.86 (m, 4H), 2.14 (s, 3H), 2.18 (m, 3H), 2.32 (m, 2H), 2.80 (m, 2H), 3.89 (s, 3H), 4.64 (m, 1H), 7.22 (m, 2H), 7.91 (d, J=8.12, 1H), 8.03 (s, 1H), 8.21 (s, 1H).

57%

With ammonium hydroxide; sodium carbonate In methanol; 1,2-dimethoxyethane; dichloromethane; water

403.e e) e) tert-Butyl N-{4-[4-amino-1-[1-(1-methylpiperidin-4-yl)-piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}carbamate 3-iodo-1-[1-(1-methylpiperidin-4-yl)]-piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (2.39 g, 5.41 mmol), tert-butyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (2.08 g, 5.96 mmol), palladium tetrakistriphenyphosphine (0.375 g, 0.32 mmol) and sodium carbonate (1.38 g, 13.00 mmol) were mixed with ethylene glycol dimethyl ether (80 mL) and water (40 mL). The reaction mixture was heated at reflux overnight. Organic solvent was removed under reduced pressure and the aqueous layer was extracted with dichloromethane. The combined organic layer was washed with water then brine, dried over MgSO4, filtered and evaporated. The residue was purified by flash column chromatography using dichloromethane/methanol/ammonium hydroxide (95:5:0.5) as mobile phase to give tert-butyl N-{4-[4-amino-1-[1-(1-methylpiperidin-4-yl)-piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}carbamate (1.67 g, 57%). 1H NMR (DMSO-d6) δ 1.48 (m, 1H), 1.71 (m, 2H) 1.86 (m, 4H), 2.14 (s, 3H), 2.18 (m, 3H), 2.32 (m, 2H), 2.80 (m, 2H), 3.89 (s, 3H), 4.64 (m, 1H), 7.22 (m, 2H), 7.91 (d, J=8.12, 1H), 8.03 (s, 1H), 8.21 (s, 1H).

12
benzyl 4-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-piperidinecarboxylate [ No CAS ]
[ 262433-02-3 ]
[ 330794-21-3 ]
Trans N₁-{4-[4-amino-1-(4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-2-phenyl-1-cyclopropanecarboxamide maleate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate In 1,2-dimethoxyethane; water	b b b Benzyl 4-(4-amino-3-{4-[(tert-butoxycarbonyl)amino]-3-methoxyphenyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-piperidinecarboxylate A mixture of benzyl 4-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-piperidinecarboxylate (7.0 g, 0.0146 mol), tert-butyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (6.15 g, 0.0176 mol), tetrakis(triphenylphosphine)palladium (1.0 g, 0.000876 mol) and sodium carbonate (3.9 g, 0.0365 mol) in ethylene glycol dimethyl ether (170 mL) and water (70 mL) was heated at 75° C. for 16 hours under an atmosphere of nitrogen. After addition of tert-butyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (6.15 g, 0.0176 mol, 1.2 eq.) and tetrakis(triphenylphosphine)palladium (1.0 g, 0.000876 mol) the mixture was stirred at 85° C. for additional 16 hours. The mixture was allowed to cool to ambient temperature and ethylene glycol dimethyl ether was removed under reduced pressure. The aqueous layer was extracted with ethyl acetate (3*150 mL). The combined organic extracts were washed with water, saturated aqueous sodium bicarbonate solution, and brine, and dried over magnesium sulfate. The solvents were evaporated under the reduced pressure to leave a brownish solid which was purified by flash column chromatography on silica using 20%-40% ethyl acetate/dichloromethane followed by 2%-5% methanol/dichloromethane as a mobile phase to give benzyl 4-(4-amino-3-{4-[(tert-butoxycarbonyl)amino]-3-methoxyphenyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-piperidinecarboxylate (8.0 g, 0.014 mol). RP-HPLC (Delta Pak C18, 5 μm, 300 A, 15 cm; 5%-85% acetonitrile-0.1M ammonium acetate over 10 min, 1 mL/min) Rt 12.6 min. MS: MH+ 574
	With sodium carbonate In 1,2-dimethoxyethane; water	487.b b) b) Benzyl 4-(4-amino-3-{4-[(tert-butoxycarbonyl)amino]-3-methoxyphenyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-piperidinecarboxylate A mixture of benzyl 4-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-piperidinecarboxylate (7.0 g, 0.0146 mol), tert-butyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (6.15 g, 0.0176 mol), tetrakis(triphenylphosphine)palladium (1.0 g, 0.000876 mol) and sodium carbonate (3.9 g, 0.0365 mol) in ethylene glycol dimethyl ether (170 mL) and water (70 mL) was heated at 75° C. for 16 hours under an atmosphere of nitrogen. After addition of tert-butyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (6.15 g, 0.0176 mol, 1.2 eq.) and tetrakis(triphenylphosphine)palladium (1.0 g, 0.000876 mol) the mixture was stirred at 85° C. for additional 16 hours. The mixture was allowed to cool to ambient temperature and ethylene glycol dimethyl ether was removed under reduced pressure. The aqueous layer was extracted with ethyl acetate (3*150 mL). The combined organic extracts were washed with water, saturated aqueous sodium bicarbonate solution, and brine, and dried over magnesium sulfate. The solvents were evaporated under the reduced pressure to leave a brownish solid which was purified by flash column chromatography on silica using 20%-40% ethyl acetate/dichloromethane followed by 2%-5% methanol/dichloromethane as a mobile phase to give benzyl 4-(4-amino-3-{4-[(tert-butoxycarbonyl)amino]-3-methoxyphenyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-piperidinecarboxylate (8.0 g, 0.014 mol). RP-HPLC (Delta Pak C18, 5 μm, 300 A, 15 cm; 5%-85% acetonitrile-0.1M ammonium acetate over 10 min, 1 mL/min) Rt 12.6 min. MS: MH+ 574.

Reference： [1]Current Patent Assignee: ABBVIE INC - US2002/156081, 2002, A1
[2]Current Patent Assignee: ABBVIE INC - US6921763, 2005, B2

13
[ 330793-99-2 ]
[ 262433-02-3 ]
tert-butyl N-(4-{4-amino-1-[4-nitrophenyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.431 g, (63%)	With sodium carbonate In <i>N</i>-methyl-acetamide; water	4-amino-1-[4-nitrophenyl]-3-iodo-1H-pyrazolo[3,4-d]pyrimidine Acetonitrile over 5 min, 3.0 to 3.5 mil/min) tR=3.73 min (100%) M+380.6. tert-butyl N-(4-{4-amino-1-[4-nitrophenyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)carbamate A suspension of 4-amino-1-[4-nitrophenyl]-3-iodo-1H-pyrazolo[3,4-d]pyrimidine (0.500 g, 1.31 mmol) in dimethylformamide (8 mL) was treated with tert-butyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (0.915 g, 2.62 mmol), tetrakis(triphenylphosphine)palladium (0.091 g, 0.06 mmol), and a solution of sodium carbonate (0.333 g, 3.14 mmol) in water (4 mL). The reaction mixture stirred at 85° C. for 26 h under a nitrogen atmosphere. Water was added to the reaction mixture. The precipitate was filtered and washed with water. The solid was triturated with diethyl ether to give 0.431 g, (63%) of tert-butyl N-(4-{4-amino-1-[4-nitrophenyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)carbamate. 1H NMR (DMSO-d6, 400 MHz) δ 8.6862-8.6634 (d, 2H, J=9.12 Hz), 8.4897-8.4423 (m, 3H), 8.1117 (s, 1H), 8.0074-7.9872 (d, 1H, J=8.08 Hz), 7.3743-7.3293 (m, 2H), 3.9189 (s, 3H), 1.4959 (s, 9H); LCMS (Perkin Elmer, Pecosphere Cl 8 column, 3um particle size, 33*4.6 mm; 100% 50 mM ammonium Acetate in Water to 100% Acetonitrile over 5 min, 3.0 to 3.5 mil/min) tR=4.38 min M+ 478.1.
0.431 g, (63%)	With sodium carbonate In <i>N</i>-methyl-acetamide; water	436 tert-butyl N-(4-{4-amino-1-[4-nitrophenyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)carbamate tert-butyl N-(4-{4-amino-1-[4-nitrophenyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)carbamate A suspension of 4-amino-1-[4-nitrophenyl]-3-iodo-1H-pyrazolo[3,4-d]pyrimidine (0.500 g, 1.31 mmol) in dimethylformamide (8 mL) was treated with tert-butyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (0.915 g, 2.62 mmol), tetrakis(triphenylphosphine)palladium (0.091 g, 0.06 mmol), and a solution of sodium carbonate (0.333 g, 3.14 mmol) in water (4 mL). The reaction mixture stirred at 85° C. for 26 h under a nitrogen atmosphere. Water was added to the reaction mixture. The precipitate was filtered and washed with water. The solid was triturated with diethyl ether to give 0.431 g, (63%) of tert-butyl N-(4-{4-amino-1-[4-nitrophenyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)carbamate. 1H NMR (DMSO-d6, 400 MHz) δ 8.6862-8.6634 (d, 2H, J=9.12 Hz), 8.4897-8.4423 (m, 3H), 8.1117 (s, 1H), 8.0074-7.9872 (d, 1H, J=8.08 Hz), 7.3743-7.3293 (m, 2H), 3.9189 (s, 3H), 1.4959 (s, 9H); LCMS (Perkin Elmer, Pecosphere C18 column, 3 um particle size, 33*4.6 mm; 100% 50 mM ammonium Acetate in Water to 100% Acetonitrile over 5 min, 3.0 to 3.5 mil/min) tR=4.38 min M+ 478.1.
0.431 g, (63%)	With sodium carbonate In <i>N</i>-methyl-acetamide; water	451 tert-butyl N-(4-{4-amino-1-[4-nitrophenyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)carbamate tert-butyl N-(4-{4-amino-1-[4-nitrophenyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)carbamate A suspension of 4-amino-1-[4-nitrophenyl]-3-iodo-1H-pyrazolo[3,4-d]pyrimidine (0.500 g, 1.31 mmol) in dimethylformamide (8 mL) was treated with tert-butyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (0.915 g, 2.62 mmol), tetrakis(triphenylphosphine)palladium (0.091 g, 0.06 mmol), and a solution of sodium carbonate (0.333 g, 3.14 mmol) in water (4 mL). The reaction mixture stirred at 85° C. for 26 h under a nitrogen atmosphere. Water was added to the reaction mixture. The precipitate was filtered and washed with water. The solid was triturated with diethyl ether to give 0.431 g, (63%) of tert-butyl N-(4-{4-amino-1-[4-nitrophenyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)carbamate. 1H NMR (DMSO-d6, 400 MHz) δ 8.6862-8.6634 (d, 2H, J=9.12 Hz), 8.4897-8.4423 (m, 3H), 8.1117 (s, 1H), 8.0074-7.9872 (d, 1H, J=8.08 Hz), 7.3743-7.3293 (m, 2H), 3.9189 (s, 3H), 1.4959 (s, 9H); LCMS (Perkin Elmer, Pecosphere C18 column, 3 um particle size, 33*4.6 mm; 100% 50 mM ammonium Acetate in Water to 100% Acetonitrile over 5 min, 3.0 to 3.5 mil/min) tR=4.38 min M+ 478.1.

14
[ 330793-53-8 ]
[ 262433-02-3 ]
tert-butyl N-(4-{4-amino-1-[1-(1H-2-imidazolylmethyl)-4-piperidyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
41%	With sodium carbonate In methanol; 1,2-dimethoxyethane; dichloromethane; water	215.b b b tert-Butyl N-(4-{4-amino-1-[1-(1H-2-imidazolylmethyl)-4-piperidyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)carbamate 1-[1-(1H-2-Imidazolylmethyl)-4-piperidyl]-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (127 mg, 0.299 mmol), tert-butyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (115 mg, 0.329 mmol), palladium tetrakistriphenyphosphine (21 mg, 0.018 mmol) and sodium carbonate (76 mg, 0.718 mmol) were mixed with ethylene glycol dimethyl ether (3 mL) and water (1.5 mL). The reaction mixture was heated at reflux overnight. Organic solvent was removed under reduced pressure and the aqueous layer was extracted with dichloromethane. The combined organic layer was washed with water then brine, dried over MgSO4, filtered and evaporated. The residue was purified by flash column chromatography using dichloromethane/methanol (95:5) as mobile phase to give tert-butyl N-(4-{4-amino-1-[1-(1H-2-imidazolylmethyl)-4-piperidyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)carbamate (64 mg, 41%). 1H NMR (DMSO-d6) δ 1.48 (m, 9H), 1.87 (m, 2H), 2.23 (m, 4H), 2.94 (m, 2H), 3.56 (s, 2H), 3.88 (s, 3H), 4.66 (m, 1H), 6.92(s, 2H), 7.21 (m, 2H), 7.90 (d, J=8.14, 1H), 8.04 (s, 1H), 8.22 (s, 1H).
41%	With sodium carbonate In methanol; 1,2-dimethoxyethane; dichloromethane; water	215.b b) b) tert-Butyl N-(4-{4-amino-1-[1-(1H-2-imidazolylmethyl)-4-piperidyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)carbamate 1-[1-(1H-2-Imidazolylmethyl)-4-piperidyl]-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (127 mg, 0.299 mmol), tert-butyl N-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (115 mg, 0.329 mmol), palladium tetrakistriphenyphosphine (21 mg, 0.018 mmol) and sodium carbonate (76 mg, 0.718 mmol) were mixed with ethylene glycol dimethyl ether (3 mL) and water (1.5 mL). The reaction mixture was heated at reflux overnight. Organic solvent was removed under reduced pressure and the aqueous layer was extracted with dichloromethane. The combined organic layer was washed with water then brine, dried over MgSO4, filtered and evaporated. The residue was purified by flash column chromatography using dichloromethane/methanol (95:5) as mobile phase to give tert-butyl N-(4-{4-amino-1-[1-(1H-2-imidazolylmethyl)-4-piperidyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)carbamate (64 mg, 41%). 1H NMR (DMSO-d6) δ 1.48 (m, 9H), 1.87 (m, 2H), 2.23 (m, 4H), 2.94 (m, 2H), 3.56 (s, 2H), 3.88 (s, 3H), 4.66 (m, 1H), 6.92(s, 2H), 7.21 (m, 2H), 7.90 (d, J=8.14, 1H), 8.04 (s, 1H), 8.22 (s, 1H).

Reference： [1]Current Patent Assignee: ABBVIE INC - US2002/156081, 2002, A1
[2]Current Patent Assignee: ABBVIE INC - US6921763, 2005, B2

16
[ 461699-81-0 ]
[ 24424-99-5 ]
[ 262433-02-3 ]

Yield	Reaction Conditions	Operation in experiment
64%	at 80℃; for 12h;	The synthetic of <strong>[461699-81-0]4-amino-3-methoxyphenylboronic acid pinacol ester</strong> is carried out as described in example 6. After completion of pinacolisation and phase separation the mixture is, however, not concentrated, rather the remaining organic phase is azeotropically dried. The residue, after adding 17.9 g (82.0 mmole) of di-tert-butyl-dicarbonate (boc-anhydride) is stirred at 80 C. for 12 h. Thereafter the bulk of the solvent is removed by distillation and the mixture is cooled to -5 C. Thereby the product crystallizes in the form of colorless crystals and can be isolated by filtration. Thus, 10.5 g (30.1 mmole, 64%) [2-methoxy-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-carbamine acid-tert-butylester are obtained.Yield over all steps: 44%.

Reference： [1]Patent: US2008/269523,2008,A1 .Location in patent: Page/Page column 6-7

17
[ 286961-24-8 ]
[ 262433-02-3 ]
[ 1124330-11-5 ]

Yield	Reaction Conditions	Operation in experiment
95%	With sodium hydrogencarbonate In 1,2-dimethoxyethane; water at 80℃; for 16h;	31 Pd(PPh3 )4 (0.66 g) was added to benzyl 4-(trifluoromethylsulfonyloxy)-3,6-dihydro-2H- pyridine-1-carboxylate (Tetrahedron Lett. 2000, 41(19), 3705) (17.1 g) and 4-(tert-0 butoxycarbonylamino)-3-methoxyphenyl-boronic acid pinacol ester (in Example 1 of WO 00/017202, page 67) (10.2 g) in a mixture of DME (210 mL) and sat.aq. NaHCO3 (210 mL). The mixture was heated to 800C for 16h then cooled and diluted with water (200 mL). The phases were separated and the aqueous phase was extracted with EtOAc (1 x 250 mL, 1 x 350 mL). The combined organic portions were dried (Na2SO4) and concentrated in5 vacuo. Purification by FCC using 20:80 to 30:70 EtOAc-zsøhexane, afforded the title compound (11.81 g, 95%) as a pale yellow liquid; 1H NMR: 1.47 (9H, s), 2.46-2.48 (2H, m), 3.61-3.65 (2H, m), 3.85 (3H, s), 4.08-4.12 (2H, m), 5.13 (2H, s), 6.13-6.17 (IH, m), 6.96-6.98 (IH, m), 7.05 (IH, d), 7.32-7.40 (5H, m), 7.68 (IH, d), 7.85 (IH, s); m/z: MH+ 439.

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2009/24824, 2009, A1 Location in patent: Page/Page column 91

18
[ 109-04-6 ]
[ 262433-02-3 ]
[ 1224708-53-5 ]

Yield	Reaction Conditions	Operation in experiment
51%	With potassium carbonate In 1,2-dimethoxyethane; water at 100℃; for 20h; Inert atmosphere;	14 Tetrakis (triphenylphosphine) palladium (0.303 g, 0.26 mmol) was added to a stirred mixture of tert-butyl (2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamate (US2005/020619, 2.20 g, 6.29 mmol), 2-bromopyridine (0.5 ml, 5.24 mmol) and a 2M aqueous solution of potassium carbonate (7 ml, 14 mmol) in DME (7 ml) under argon. The resulting solution was stirred at 100° C. for 20 hours. The reaction mixture was allowed to cool to room temperature, quenched with water and extracted with ethyl acetate. The organic phase was washed with brine, dried over magnesium sulfate, concentrated then purified by flash chromatography on silica gel eluting with 5 to 20% ethyl acetate in petroleum ether to afford tert-butyl N-[2-methoxy-4-(2-pyridyl)phenyl]carbamate (0.813 g, 51%); NMR spectrum: 1.48 (s, 9H), 3.91 (s, 3H), 7.31 (ddd, 1H), 7.65 (dd, 1H), 7.73 (d, 1H), 7.83-7.88 (m, 2H), 7.97 (d, 1H), 8.00 (s, 1H), 8.64 (ddd, 1H).

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - US2010/105655, 2010, A1 Location in patent: Page/Page column 169

19
[ 138647-49-1 ]
[ 262433-02-3 ]
[ 1224708-46-6 ]

Yield	Reaction Conditions	Operation in experiment
80%	With sodium hydrogencarbonate In 1,2-dimethoxyethane; water at 90℃;	12 A mixture of tert-butyl 4-(trifluoromethylsulfonyloxy)-5,6-dihydropyridine-1(2H)-carboxylate (Journal of Medicinal Chemistry, 2006, vol. 49, p. 7450, 3.8 g, 11.4 mmol), tert-butyl (2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamate (US2005/020619, 4.41 g, 12.6 mmol), a saturated aqueous solution of sodium bicarbonate (20 mL) and tetrakis (triphenylphosphine) palladium (0.265 g, 0.23 mmol) in dimethoxyethane (40 mL) was stirred at 90° C. overnight. The reaction mixture was diluted with water and extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO4 and concentrated. The crude product was purified by flash chromatography on silica gel eluting with 0 to 20% ethyl acetate in petroleum ether to afford tert-butyl 4-(4-(tert-butoxycarbonylamino)-3-methoxyphenyl)-5,6-dihydropyridine-1(2H)-carboxylate (3.70 g, 80%) as a pale yellow foam; NMR spectrum: 1.43 (s, 9H), 1.45 (s, 9H), 2.42-2.48 (m, 2H), 3.50-3.57 (m, 2H), 3.83 (s, 3H), 3.99 (bs, 2H), 6.12 (bs, 1H), 6.96 (dd, 1H), 7.03 (d, 1H), 7.65 (d, 1H), 7.87 (s, 1H).

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - US2010/105655, 2010, A1 Location in patent: Page/Page column 168-169

20
[ 443680-33-9 ]
[ 262433-02-3 ]
[ 1224708-50-2 ]

Yield	Reaction Conditions	Operation in experiment
83%	With caesium carbonate In tetrahydrofuran at 25℃; for 3.75h; Inert atmosphere; Reflux;	13 (1,1'-bis-(diphenylphosphino)-ferrocene) palladium dichloride (34.0 mg, 0.04 mmol) and cesium carbonate (821 mg, 2.52 mmol) in water (1 ml) were added to a stirred solution of tert-butyl (2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamate (US2005/020619, 440 mg, 1.26 mmol) and tert-butyl 2-oxo-4-(tosyloxy)-2,5-dihydro-1H-pyrrole-1-carboxylate (Journal of Organic Chemistry, 2002, vol. 67, p. 4702, 297 mg, 0.84 mmol) in THF (10 ml) under argon. The resulting solution was stirred at 25° C. for 45 min then reflux for 3 hours. After cooling, the mixture was filtered and evaporated to dryness. The crude product was taken up in EtOAc, washed with a saturated solution of bicarbonate, then brine. After evaporation, the residue was purified by flash chromatography on silica gel eluting with 0 to 40% EtOAc/petroleum ether to afford tert-butyl 4-(4-(tert-butoxycarbonylamino)-3-methoxyphenyl)-2-oxo-2,5-dihydro-1H-pyrrole-1-carboxylate (283 mg, 83%) as a white solid.

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - US2010/105655, 2010, A1 Location in patent: Page/Page column 169

21
[ 262433-02-3 ]
N-(4-(4-amino-7-(cis-4-(3-methyl-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)cyclohexyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methoxyphenyl)-1-methyl-1H-indole-2-carboxamidamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate / 1,2-dimethoxyethane; ethanol / 80 °C / Inert atmosphere 2.1: hydrogenchloride / water; acetone; methanol / 2 h / Reflux 3.1: pyridine / dichloromethane / 0.08 h / Cooling with ice 3.2: 0.5 h / Cooling with ice 4.1: acetic acid; sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 20 °C

Reference： [1]Current Patent Assignee: INSTITUTE OF PHYSICAL AND CHEMICAL RESEARCH (RIKEN) - EP2878601, 2015, A1

22
[ 262433-02-3 ]
N-(4-(4-amino-7-((trans)-4-(3-methyl-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)cyclohexyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methoxyphenyl)-1-methyl-1H-indole-2-carboxamide [ No CAS ]
N-(4-(4-amino-7-(cis-4-(3-methyl-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)cyclohexyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methoxyphenyl)-1-methyl-1H-indole-2-carboxamidamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate / 1,2-dimethoxyethane; ethanol / 80 °C / Inert atmosphere 2.1: hydrogenchloride / water; acetone; methanol / 2 h / Reflux 3.1: pyridine / dichloromethane / 0.08 h / Cooling with ice 3.2: 0.5 h / Cooling with ice 4.1: acetic acid; sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 20 °C

Reference： [1]Current Patent Assignee: INSTITUTE OF PHYSICAL AND CHEMICAL RESEARCH (RIKEN) - EP2878601, 2015, A1

23
[ 262433-02-3 ]
N-(4-(4-amino-7-(trans-4-(4-methylpiperazin-1-yl)cyclohexyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methoxyphenyl)-1-methyl-1H-indole-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate / 1,2-dimethoxyethane; ethanol / 80 °C / Inert atmosphere 2.1: hydrogenchloride / water; acetone; methanol / 2 h / Reflux 3.1: pyridine / dichloromethane / 0.08 h / Cooling with ice 3.2: 0.5 h / Cooling with ice 4.1: acetic acid; sodium tris(acetoxy)borohydride / 1,2-dichloro-ethane / 20 °C

Reference： [1]Current Patent Assignee: INSTITUTE OF PHYSICAL AND CHEMICAL RESEARCH (RIKEN) - EP2878601, 2015, A1

24
[ 262433-02-3 ]
N-(4-(4-amino-7-(4-oxocyclohexyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methoxyphenyl)-1-methyl-1H-indole-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate / 1,2-dimethoxyethane; ethanol / 80 °C / Inert atmosphere 2.1: hydrogenchloride / water; acetone; methanol / 2 h / Reflux 3.1: pyridine / dichloromethane / 0.08 h / Cooling with ice 3.2: 0.5 h / Cooling with ice

Reference： [1]Current Patent Assignee: INSTITUTE OF PHYSICAL AND CHEMICAL RESEARCH (RIKEN) - EP2878601, 2015, A1

25
[ 262433-02-3 ]
[ 262444-50-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate / 1,2-dimethoxyethane; ethanol / 80 °C / Inert atmosphere 2: hydrogenchloride / water; acetone; methanol / 2 h / Reflux

Reference： [1]Current Patent Assignee: INSTITUTE OF PHYSICAL AND CHEMICAL RESEARCH (RIKEN) - EP2878601, 2015, A1

26
[ 943974-70-7 ]
[ 262433-02-3 ]
tert-butyl (4-(4-amino-7-(4-oxocyclohexyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methoxyphenyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.7 g	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate In 1,2-dimethoxyethane; ethanol at 80℃; Inert atmosphere;	4.1 N-(4-(4-amino-7-((trans)-4-(3-methyl-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H )-yl)cyclohexyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methoxyphenyl)-1-methyl-1H-indole-2-carboxamide tert-Butyl (4-(4-amino-7-(4-oxocyclohexyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methoxyphenyl)carba mate tert-Butyl (2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamate (0.6 g, 1.74 mmol) was dissolved in ethylene glycol dimethyl ether (74 mL) and ethanol (20 mL), and 4-(4-amino-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclohexanone (0.5 g, 1.45 mmol), a saturated sodium carbonate solution (8.6 mL) and tetrakis(triphenylphosphine)palladium (117 mg, 0.10 mmol) were sequentially added thereto. The mixture was stirred overnight in an argon atmosphere at 80°C. The mixture was left to cool, subsequently dichloromethane was added thereto, and the mixture was extracted. The extract was partitioned and washed with saturated brine. The organic layer was dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. A pale brown oily substance (0.9 g) thus obtained was purified by silica gel column chromatography (dichloromethane/methanol = 95/5), and tert-butyl (4-(4-amino-7-(4-oxocyclohexyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methoxyphenyl)carba mate (0.7 g) was obtained.

Reference： [1]Current Patent Assignee: INSTITUTE OF PHYSICAL AND CHEMICAL RESEARCH (RIKEN) - EP2878601, 2015, A1 Location in patent: Paragraph 0168

27
[ 214342-63-9 ]
[ 262433-02-3 ]
(2-methoxy-4-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)phenyl)carbamic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98.2%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 90℃; for 6h;Inert atmosphere;	(2-methoxy-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl) carbamic acid Ester (1.2 g, 3.4 mmol),Bromo-1-methylpyridin-2 (1H) -one (0.64 g, 3.4 mmol) and potassium carbonate (0.94 g, 6.8 mmol)Was added to 1,4-dioxane (100 mL) and water (20 mL)1,1'-bis (diphenylphosphino) ferrocene palladium dichloride (249 mg, 0.34 mmol) was added under nitrogen atmosphere,The reaction was heated to 90 C for 6 hours,The filtrate was concentrated and the crude product was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 5: 1) to give the title compound (1.1 g, yield 98.2%).
58.0%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 90℃;Inert atmosphere;	(0681) Tert-butyl (2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)amino carboxylate (1.49 g, 4.26 mmol), <strong>[214342-63-9]4-bromo-1-methylpyridin-2(1H)-one</strong> (800 mg, 4.26 mmol) and potassium carbonate (1.18 g, 8.55 mmol) were added to 1,4-dioxane (50 mL) and water (10 mL). Under the protection of nitrogen gas, after the addition of [1,1?-bis(diphenyphosphino)ferrocene]dichloropalladium ( II) (190 mg, 0.26 mmol), the temperature was increased to 90 C. The reaction mixture was stirred overnight, and filtrated under suction. The filtrate was concentrated, and the crude product was purified by silica gel column chromatography (petroleum ether:ethyl acetate=5:1) to get the title compound (816 mg, yield: 58.0%).

Reference： [1]Patent: CN105884695,2016,A .Location in patent: Paragraph 0363; 0364; 0365
[2]Patent: US2017/112833,2017,A1 .Location in patent: Paragraph 0680-0681

28
[ 262433-02-3 ]
N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((2-((2-methoxy-4-(1-methyl-2-oxopiperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)amino)phenyl)acrylamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 9 steps 1.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate / water; 1,4-dioxane / 6 h / 90 °C / Inert atmosphere 2.1: platinum(IV) oxide; hydrogen / methanol / 16 h / 20 °C 3.1: trifluoroacetic acid / dichloromethane / 0.5 h / 20 °C 4.1: zinc(II) chloride / diethyl ether; <i>tert</i>-butyl alcohol; 1,2-dichloro-ethane / 1 h / 0 °C 4.2: 16 h / 25 °C 5.1: hydrogenchloride / water; 1,4-dioxane / 2 h / 100 °C 6.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / 85 °C 7.1: hydrogen; palladium 10% on activated carbon / methanol / 1.5 h / 25 °C 8.1: tetrahydrofuran; water / 2 h / 25 °C 9.1: sodium hydroxide / 7 h / 65 °C

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - CN105884695, 2016, A

29
[ 262433-02-3 ]
(2-methoxy-4-(1-methyl-2-oxopiperidin-4-yl)phenyl)carbamic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate / water; 1,4-dioxane / 6 h / 90 °C / Inert atmosphere 2: platinum(IV) oxide; hydrogen / methanol / 16 h / 20 °C
	Multi-step reaction with 2 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate / water; 1,4-dioxane / 90 °C / Inert atmosphere 2: hydrogen; platinum(IV) oxide / methanol / 20 °C

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - CN105884695, 2016, A
[2]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - US2017/112833, 2017, A1

30
[ 262433-02-3 ]
4-(4-amino-3-methoxyphenyl)-1-methylpiperidin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate / water; 1,4-dioxane / 6 h / 90 °C / Inert atmosphere 2: platinum(IV) oxide; hydrogen / methanol / 16 h / 20 °C 3: trifluoroacetic acid / dichloromethane / 0.5 h / 20 °C
	Multi-step reaction with 3 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate / water; 1,4-dioxane / 90 °C / Inert atmosphere 2: hydrogen; platinum(IV) oxide / methanol / 20 °C 3: trifluoroacetic acid / dichloromethane / 0.5 h / 20 °C

31
[ 262433-02-3 ]
4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3-methoxyphenyl)-1-methylpiperidin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate / water; 1,4-dioxane / 6 h / 90 °C / Inert atmosphere 2.1: platinum(IV) oxide; hydrogen / methanol / 16 h / 20 °C 3.1: trifluoroacetic acid / dichloromethane / 0.5 h / 20 °C 4.1: zinc(II) chloride / diethyl ether; <i>tert</i>-butyl alcohol; 1,2-dichloro-ethane / 1 h / 0 °C 4.2: 16 h / 25 °C

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - CN105884695, 2016, A

32
[ 262433-02-3 ]
4-(4-((4-((4-fluoro-2-methoxy-5-nitrophenyl)amino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3-methoxyphenyl)-1-methylpiperidin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate / water; 1,4-dioxane / 6 h / 90 °C / Inert atmosphere 2.1: platinum(IV) oxide; hydrogen / methanol / 16 h / 20 °C 3.1: trifluoroacetic acid / dichloromethane / 0.5 h / 20 °C 4.1: zinc(II) chloride / diethyl ether; <i>tert</i>-butyl alcohol; 1,2-dichloro-ethane / 1 h / 0 °C 4.2: 16 h / 25 °C 5.1: hydrogenchloride / water; 1,4-dioxane / 2 h / 100 °C

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - CN105884695, 2016, A

33
[ 262433-02-3 ]
4-(4-((4-((4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy-5-nitrophenyl)amino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3-methoxyphenyl)-1-methylpiperidin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate / water; 1,4-dioxane / 6 h / 90 °C / Inert atmosphere 2.1: platinum(IV) oxide; hydrogen / methanol / 16 h / 20 °C 3.1: trifluoroacetic acid / dichloromethane / 0.5 h / 20 °C 4.1: zinc(II) chloride / diethyl ether; <i>tert</i>-butyl alcohol; 1,2-dichloro-ethane / 1 h / 0 °C 4.2: 16 h / 25 °C 5.1: hydrogenchloride / water; 1,4-dioxane / 2 h / 100 °C 6.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / 85 °C

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - CN105884695, 2016, A

34
[ 262433-02-3 ]
4-(4-((4-((5-amino-4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxyphenyl)amino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3-methoxyphenyl)-1-methylpiperidin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate / water; 1,4-dioxane / 6 h / 90 °C / Inert atmosphere 2.1: platinum(IV) oxide; hydrogen / methanol / 16 h / 20 °C 3.1: trifluoroacetic acid / dichloromethane / 0.5 h / 20 °C 4.1: zinc(II) chloride / diethyl ether; <i>tert</i>-butyl alcohol; 1,2-dichloro-ethane / 1 h / 0 °C 4.2: 16 h / 25 °C 5.1: hydrogenchloride / water; 1,4-dioxane / 2 h / 100 °C 6.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / 85 °C 7.1: hydrogen; palladium 10% on activated carbon / methanol / 1.5 h / 25 °C

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - CN105884695, 2016, A

35
[ 262433-02-3 ]
3-chloro-N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((2-((2-methoxy-4-(1-methyl-2-oxopiperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidine-4-yl)amino)phenyl)propanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 8 steps 1.1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate / water; 1,4-dioxane / 6 h / 90 °C / Inert atmosphere 2.1: platinum(IV) oxide; hydrogen / methanol / 16 h / 20 °C 3.1: trifluoroacetic acid / dichloromethane / 0.5 h / 20 °C 4.1: zinc(II) chloride / diethyl ether; <i>tert</i>-butyl alcohol; 1,2-dichloro-ethane / 1 h / 0 °C 4.2: 16 h / 25 °C 5.1: hydrogenchloride / water; 1,4-dioxane / 2 h / 100 °C 6.1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / 85 °C 7.1: hydrogen; palladium 10% on activated carbon / methanol / 1.5 h / 25 °C 8.1: tetrahydrofuran; water / 2 h / 25 °C

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - CN105884695, 2016, A

36
[ 24424-99-5 ]
[ 262433-02-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: tetrahydrofuran / 22 h / Inert atmosphere; Reflux 2: potassium acetate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / N,N-dimethyl-formamide / 80 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - US2017/112833, 2017, A1

37
[ 262433-02-3 ]
N-(3-((2-((2-methoxy-4-(1-methyl-2-oxopiperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)amino)phenyl)acrylamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate / water; 1,4-dioxane / 90 °C / Inert atmosphere 2: hydrogen; platinum(IV) oxide / methanol / 20 °C 3: trifluoroacetic acid / dichloromethane / 0.5 h / 20 °C 4: trifluoroacetic acid / isopropyl alcohol / 70 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - US2017/112833, 2017, A1

38
[ 59557-91-4 ]
[ 262433-02-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: tetrahydrofuran / 22 h / Inert atmosphere; Reflux 2: potassium acetate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / N,N-dimethyl-formamide / 80 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: SIHUAN PHARMACEUTICAL HOLDINGS GROUP LTD. - US2017/112833, 2017, A1

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Historical Records

Related Functional Groups of
[ 262433-02-3 ]

Organoboron

[ 1105710-32-4 ]

6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]oxazol-2(3H)-one

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tert-Butyl (4-hydroxy-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamate

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Aryls

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tert-Butyl (4-hydroxy-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamate

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Amides

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3-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]oxazol-2(3H)-one

Similarity: 0.89

[ 1384312-65-5 ]

tert-Butyl (4-hydroxy-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamate

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Esters

[ 1914078-87-7 ]

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Similarity: 0.95

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[ N/A ]

tert-Butyl (4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)phenyl)carbamate

Similarity: 0.93

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[ N/A ]

tert-Butyl (3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)phenyl)carbamate

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Amines

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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

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 262433-02-3 ]

Quality Control of [ 262433-02-3 ]

Related Doc. of [ 262433-02-3 ]

Product Details of [ 262433-02-3 ]

Safety of [ 262433-02-3 ]

Application In Synthesis of [ 262433-02-3 ]

[ 262433-02-3 ] Synthesis Path-Upstream 1~1

[ 262433-02-3 ] Synthesis Path-Downstream 1~38

Related Functional Groups of [ 262433-02-3 ]

Organoboron

Aryls

Amides

Esters

Amines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 262433-02-3 ]