Name: 1104637-36-6|Cyclopropylboronic acid MIDA ester|97%
Brand: Ambeed
SKU: A148654
Price: 17.0 USD
Availability: InStock
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1
[ 186581-53-3 ]
[ 1104636-73-8 ]
[ 1104637-36-6 ]

Reference： [1]Tetrahedron,2009,vol. 65,p. 3130 - 3138

2
[ 1104637-36-6 ]
[ 7732-18-5 ]
[ 411235-57-9 ]

Yield	Reaction Conditions	Operation in experiment
	In not given hydrolysis of appropriate N-methyliminodiacetic acid boronate;

Reference： [1]Knapp, David M.; Gillis, Eric P.; Burke, Martin D. [Journal of the American Chemical Society, 2009, vol. 131, p. 6961 - 6963]

3
[ 1104637-36-6 ]
[ 411235-57-9 ]

Yield	Reaction Conditions	Operation in experiment
53%	With sodium hydroxide In tetrahydrofuran; water at 23℃; for 0.333333h;

Reference： [1]Knapp, David M.; Gillis, Eric P.; Burke, Martin D. [Journal of the American Chemical Society, 2009, vol. 131, p. 6961 - 6963]

4
[ 1104637-36-6 ]
[ 7051-13-0 ]
[ 1158985-15-9 ]

Yield	Reaction Conditions	Operation in experiment
97%	Stage #1: cyclopropylboronic acid methyliminodiacetic acid ester; 1-chloro-2,4-dimethoxybenzene With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate In 1,4-dioxane at 23℃; for 0.166667h; Inert atmosphere; Stage #2: With potassium phosphate; water In 1,4-dioxane at 23 - 100℃; for 6.5h; Inert atmosphere;

Reference： [1]Knapp, David M.; Gillis, Eric P.; Burke, Martin D. [Journal of the American Chemical Society, 2009, vol. 131, p. 6961 - 6963]

5
[ 1104637-36-6 ]
[ 1667-04-5 ]
[ 26269-59-0 ]

Yield	Reaction Conditions	Operation in experiment
79%	Stage #1: cyclopropylboronic acid methyliminodiacetic acid ester; 2-bromomesitylene With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate In 1,4-dioxane at 23℃; for 0.166667h; Inert atmosphere; Stage #2: With potassium phosphate; water In 1,4-dioxane at 23 - 100℃; for 24.5h; Inert atmosphere;

Reference： [1]Knapp, David M.; Gillis, Eric P.; Burke, Martin D. [Journal of the American Chemical Society, 2009, vol. 131, p. 6961 - 6963]

6
[ 1104637-36-6 ]
[ 18995-35-2 ]
[ 1158985-08-0 ]

Reference： [1]Journal of the American Chemical Society,2009,vol. 131,p. 6961 - 6963

7
[ 4408-64-4 ]
[ 411235-57-9 ]
[ 1104637-36-6 ]

Yield	Reaction Conditions	Operation in experiment
74%	In dimethyl sulfoxide; toluene for 2h; Reflux;
74%	In dimethyl sulfoxide; toluene for 2h; Inert atmosphere; Reflux;	1 To form protected organoboronic acid 2h (Uno, 2009), the general procedure was followed using cyclopropyl boronic acid (5.139 g, 59.82 mmol, purchased from Oakwood Products), N-methyliminodiacetic acid (10.56 g, 71.79 mmol), DMSO (20 mL) and toluene (20 mL). The mixture was refluxed for 2 h. The mixture was cooled to room temperature and then was concentrated in vacuo (1 Torr, 100 0C). Although the product is stable to chromatography, for convenience the purification step was modified to employ crystallization. The residue oil was suspended in EtOAc (500 mL) and was transferred to a 2 L separatory funnel. The mixture was washed with water (250 mL). The aqueous phase was extracted with EtOAc (3 x 250 mL). The combined organics were washed with brine (50 mL) and then were dried over MgSO4, filtered, and concentrated in vacuo. The resulting crude product was dissolved in acetone (approximately 100 mL), and then was diluted slowly over 1 h with Et2O (1.5 L) to promote crystallization of the product. The mixture was filtered to isolate 2h as a colorless, crystalline solid (8.775 g, 74%). TLC (EtOAc) Rf = 0.21 , stained with KMnO4. 1H-NMR (500 MHz, CD3CN) δ 3.92 (d, / = 17 Hz, 2H), 3.80 (d, / = 1 7 Hz, 2H), 2.98 (s, 3H), 0.46 (dq, / = 9.5, 3.0 Hz, 2H), 0.12 (m, 2H), -0.33 (m, 1 H). 13C-NMR (125 MHz, acetone-d6) δ 169.0, 62.7, 46.8, 1.2. 11B-NMR (96 MHz, CD3CN) δ 13.2. HRMS (FAB + ) Calculated for C8H13BNO4 (M + H) + : 198.0938, Found: 198.0937. IR (thin film, cm -1) 2998, 1744, 1457, 1358, 1337, 2197, 1246, 1 129, 1048, 985, 956, 892, 880, 845, 704.

Reference： [1]Knapp, David M.; Gillis, Eric P.; Burke, Martin D. [Journal of the American Chemical Society, 2009, vol. 131, p. 6961 - 6963]
[2]Current Patent Assignee: UNIVERSITY OF ILLINOIS (SYSTEM) - WO2010/36921, 2010, A2 Location in patent: Page/Page column 36

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate In 1,4-dioxane-d8; water-d2	12 Stock solutions of the MIDA boronate and 4-bromoanisole (internal standard) in dioxane-dβ were prepared as follows: 4-tolyl MIDA boronate (Gillis, 2007) (16 mg, 0.064 mmol) and 4-bromoanisole (12 mg, 0.065 mmol) were dissolved in dioxane-dβ (800 microliters); 2-furyl MIDA boronate (2a) (54 mg, 0.24 mmol) and 4-bromoanisole (45 mg, 24 mmol) were dissolved in dioxane-dβ (3.0 mL); vinyl MIDA boronate (2g) (1 1 .7 mg, 0.064 mmol) and 4-bromoanisole (12 mg, 0.065 mmol) were dissolved in dioxane-dβ (800 microliters); cyclopropyl MIDA boronate (2h) (12.8 mg, 0.065 mmol) and 4-bromoanisole (12.0 mg, 0.064 mmol) were dissolved in dioxane-dβ (800 microliters). To each 1 .5 mL vial equipped with a small stir bar was added the boronate stock solution (100 microliters) followed by a solution of K3PO4 in D2O (3.0 M, 20 microliters). The mixtures were stirred at the specified temperature (23 0C, 60 0C, or 100 0C) for the specified time (0.5 h, 1 .0 h, 2.0 h, etc.). The mixtures were then immediately cooled to room temperature and were diluted with CD3CN (0.5 mL containing TMS internal standard). The solutions were immediately analyzed by 1 H-NMR.

9
[ 1104637-36-6 ]
[ 18242-39-2 ]
[ 1239596-32-7 ]

Yield	Reaction Conditions	Operation in experiment
69%	With caesium carbonate In water; toluene at 100℃; Inert atmosphere;	93 Example 931-Cyclopropyl-3,5-dinitrobenzene3,5-Dinitrobromobenzene (600 mg, 2.4 mmol) was added to toluene/water (10:2 ml), in a 60 ml round bottom flask fitted with a water condenser. To this solution, tricyclohexylphosphine (200 mg, 0.7 mmol), cesium carbonate (4.74 g, 14.5 mmol), cyclopropylboronic acid MIDA ester (670 mg, 3.4 mmol) were added subsequently. This mixture was degassed by bubbling N2 into the solution for 15 minutes, and finally palladium acetate (82 mg, 0.36 mmol) was added to the mixture and was heated at 100° C. with stirring under N2 overnight. The solution was cooled to room temperature. Ethyl acetate and saturated K2CO3 was added to the mixture, and the two layers were separated. Organic layer was dried with Na2SO4, after filtering off the solid, the mother liquor was concentrated under reduced pressure. The residue was purified with chromatography using ethyl acetate and hexanes (1:4) as an eluent to give the title compound as a yellow solid (350 mg, 69% yield).1H NMR (300 MHz, DMSO) δ 8.57 (s, 1H), 8.31 (s, 2H), 2.33 (m, 1H), 1.14 (d, J=6 Hz, 2H), 0.95 (m, 2H).
64%	With caesium carbonate; tricyclohexylphosphine In water; toluene for 12h; Inert atmosphere; Reflux;	3.1 In a 250 mL round bottom flask to a solution of 3-bromo 1,5-dinitrobenzene (2.1 g, 8.50 mmol) in toluene (90 mL) tricyclohexylphosphine (0.72 g, 2.55 mmol), Cs2CO3 (16.58 g, 51 mmol), cyclopropylboronic acid MIDA ester (2.35 g, 11.90 mmol) and 10 ml de-ionized water were added and the solution was degassed with nitrogen for 30 minutes. To the above solution Pd (OAc)2 (0.29 g, 1.28 mmol) was added under nitrogen and the reaction mixture was refluxed for 12 hours. LC MS analysis of the crude reaction indicated the completion of the reaction. The crude reaction mixture was filtered on celite pad and the volatiles were removed under reduced pressure. The dark brown oil was worked-up with 2×100 mL ethyl acetate and water (100 mL), dried on MgSO4 and ethyl acetate was evaporated under reduced pressure. The crude reaction mixture was separated by column chromatography to give Compound 8 in 64% yield.1H NMR (CDCl3, 300 MHz): δ 8.81 (t, J=1.92 Hz & 1.93 Hz, 1H), 8.22 (d, J=1.90 Hz, 2H), 2.14 (m, 1H), 1.23-1.26 (m, 2H), 0.90-0.92 (m, 2H); LCMS (m/z): 248 (MH+).

Reference： [1]Current Patent Assignee: RIGEL PHARMACEUTICALS INC - US2011/130415, 2011, A1 Location in patent: Page/Page column 66
[2]Current Patent Assignee: RIGEL PHARMACEUTICALS INC - US2010/204208, 2010, A1 Location in patent: Page/Page column 80-81

10
[ 1104637-36-6 ]
[ 10403-47-1 ]
[ 1239596-36-1 ]

Yield	Reaction Conditions	Operation in experiment
70%	With caesium carbonate; tricyclohexylphosphine In water; toluene for 12h; Inert atmosphere; Reflux;	4.1 In a 250 mL round bottom flask to a solution of 2-bromo 5-nitroaniline (2.30 g, 10.60 mmol) in toluene (90 mL) tricyclohexylphosphine (0.89 g, 3.18 mmol), Cs2CO3 (17.22 g, 52.99 mmol), cyclopropylboronic acid MIDA ester (2.92 g, 14.84 mmol) and 10 ml de-ionized water were added and the solution was degassed with nitrogen for 30 minutes. To the above solution Pd(OAc)2 (0.36 g, 1.59 mmol) was added under nitrogen and the reaction mixture was refluxed for 12 hours. LC MS analysis of the crude reaction indicated the completion of the reaction. The crude reaction mixture was filtered on celite pad and the volatiles were removed under reduced pressure. The dark brown oil was worked-up with 2×100 mL ethyl acetate and water (100 mL), dried on MgSO4 and ethyl acetate was evaporated under reduced pressure. The crude reaction mixture was separated by column chromatography to give Compound 13 in 70% yield.1H NMR (DMSO d6, 300 MHz): δ 7.43 (d, J=2.48 Hz, 1H), 7.26 (dd, J=1.90 Hz & 8.25 Hz, 1H), 6.95 (d, J=8.25 Hz, 1H), 5.70 (s, 2H), 1.75 (m, 1H), 0.92-0.95 (m, 2H), 0.56-0.59 (m, 2H); LCMS (m/z): 179 (MH+).
70%	With caesium carbonate; tricyclohexylphosphine In water; toluene for 12h; Inert atmosphere; Reflux;	39 Synthesis of 2-cyclopropyl 5-nitrobenzenamine Example 39 Synthesis of 2-cyclopropyl 5-nitrobenzenamine In a 250 mL round bottom flask to a solution of 2-bromo 5-nitroaniline (2.30 g, 10.60 mmol) in toluene (90 mL) tricyclohexylphosphine (0.89 g, 3.18 mmol), Cs2CO3 (17.22 g, 52.99 mmol), cyclopropylboronic acid MIDA ester (2.92 g, 14.84 mmol) and 10 ml de-ionized water were added and the solution was degassed with nitrogen for 30 minutes. To the above solution Pd(OAc)2 (0.36 g, 1.59 mmol) was added under nitrogen and the reaction mixture was refluxed for 12 hours. LC MS analysis of the crude reaction indicated the completion of the reaction. The crude reaction mixture was filtered on Celite pad and the volatiles were removed under reduced pressure. The dark brown oil was worked-up with 2*100 mL ethyl acetate and water (100 mL), dried on MgSO4 and ethyl acetate was evaporated under reduced pressure. The crude reaction mixture was separated by column chromatography to give 2-cyclopropyl-5-nitrobenzeneamine in 70% yield. 1H NMR (DMSO d6, 300 MHz): δ 7.43 (d, J=2.5 Hz, 1H), 7.26 (dd, J=1.9, 8.3 Hz, 1H), 6.95 (d, J=8.3 Hz, 1H), 5.70 (s, 2H), 1.75 (m, 1H), 0.92-0.95 (m, 2H), 0.56-0.59 (m, 2H); LCMS (m/z): 179 (MH+).

Reference： [1]Current Patent Assignee: RIGEL PHARMACEUTICALS INC - US2010/204208, 2010, A1 Location in patent: Page/Page column 81
[2]Current Patent Assignee: RIGEL PHARMACEUTICALS INC - US2012/22092, 2012, A1 Location in patent: Page/Page column 43

11
[ 1104637-36-6 ]
[ 392-95-0 ]
[ 1309831-94-4 ]

Yield	Reaction Conditions	Operation in experiment
59%	With caesium carbonate In water; toluene at 100℃; Inert atmosphere;	104 Example 1042-Cyclopropyl-1-trifluoromethyl-3,5-dinitrobenzene2-Chloro-1-(trifluoromethyl)-3,5-dinitrobenzene (5 g, 18.5 mmol) was added to toluene (91.6 ml) and water (18 ml), followed by cyclopropylboronic acid MIDA ester (5.1 g, 25.9 mmol), tricyclohexylphosphine (1.55 g, 5.5 mmol), cesium carbonate (36 g, 0.11 mol). The mixture was degassed by bubbling N2 into it for 30 minutes, and Pd(OAc)2 (620 mg, 2.76 mmol) was added. The mixture was heated at 100° C. overnight, followed by thin layer chromatography (9.75:0.25 Hexanes:Ethyl Acetate). The solution was cooled to room temperature, ethyl acetate (250 ml) and saturated NaHCO3 (250 ml) were added to the mixture. The 2 layers were separated, the organic layer washed with brine (250 ml) and dried with Na2SO4, filtered and concentrated under reduced pressure. The title compound (3 g, 59% yield) was obtained after purifying residue using flash column chromatography (9.75:0.25 Hexanes:Ethyl Acetate).1H NMR (300 MHz, DMSO) δ 8.94 (d, J=2.4 Hz, 1H), 8.62 (d, J=2.1 Hz, 1H), 2.25 (m, 1H), 1.05 (m, 2H), 0.61 (m, 2H); LCMS (m/z): 277.14 (MH+).

Reference： [1]Current Patent Assignee: RIGEL PHARMACEUTICALS INC - US2011/130415, 2011, A1 Location in patent: Page/Page column 69

12
[ 1104637-36-6 ]
[ 346433-97-4 ]
[ 1309833-21-3 ]

Yield	Reaction Conditions	Operation in experiment
81%	With caesium carbonate In water; toluene at 100℃; Inert atmosphere;	31.1 Example 31Alternative Synthesis of 1-(2-Cyclopropyl-4-fluoro-5-nitrophenyl)-4-methyl-1H-tetrazol-5(4H)-oneStep 1: 2-Cyclopropyl-4-Fluoro-5-NitroanilineA mixture of 2-bromo-4-fluoro-5-nitroaniline (12 g, 51 mmol), cyclopropylboronic acid MIDA ester (Aldrich; 20.1 g, 102 mmol), Pd(OAc)2 (1.72 g, 7.7 mmol), Cy3P (4.3 g, 15.3 mmol) and Cs2CO3 (98.8 g, 306 mmol) in toluene (120 mL) and H2O (40 mL) was de-gassed with N2 for 15 minutes. The mixture was then heated at 100° C. (oil bath temperature) overnight (the reaction mixture can also be heated to reflux). After allowing to cool to room temperature, the mixture was diluted with EtOAc (200 mL) and H2O (100 mL) and the mixture filtered through Celite. The filter cake was washed with EtOAc (2×100 mL) and the filtrate partitioned. The organic layer was dried (Na2SO4), filtered and the solvent removed under vacuum to leave a crude residue. The residue was purified by column chromatography on silica gel (residue dry-loaded on to silica gel) using EtOAc/hexanes (1:4 to 3:7) as eluent to give the product (8.1 g, 81%) as a dark solid.1H NMR (DMSO-d6, 300 MHz): δ 7.27 (d 1H), 6.84 (d, 1H), 5.52 (br. s, 2H), 1.74-1.83 (m, 1H), 0.92-0.98 (m, 2H), 0.62-0.73 (m, 2H); m/z=238.0 (M+MeCN+H)+.
81%	With caesium carbonate; tricyclohexylphosphine In water; toluene at 100℃; Inert atmosphere;	12 Synthesis of 2-cyclopropyl-4-fluoro-5-nitroaniline Example 12 Synthesis of 2-cyclopropyl-4-fluoro-5-nitroaniline A mixture of 2-bromo-4-fluoro-5-nitroaniline (12 g, 51 mmol), cyclopropylboronic acid MIDA ester (Aldrich; 20.1 g, 102 mmol), Pd(OAc)2 (1.72 g, 7.7 mmol), Cy3P (4.3 g, 15.3 mmol) and Cs2CO3 (98.8 g, 306 mmol) in toluene (120 mL) and H2O (40 mL) was de-gassed with N2 for 15 minutes. The mixture was then heated at 100° C. (oil bath temperature) overnight (the reaction mixture can also be heated to reflux). After allowing to cool to room temperature, the mixture was diluted with EtOAc (200 mL) and H2O (100 mL) and the mixture filtered through Celite. The filter cake was washed with EtOAc (2*100 mL) and the filtrate partitioned. The organic layer was dried (Na2SO4), filtered and the solvent removed under vacuum to leave a crude residue. The residue was purified by column chromatography on silica gel (residue dry-loaded on to silica gel) using EtOAc/hexanes (1:4 to 3:7) as eluent to give the product (8.1 g, 81%) as a dark solid. 1H NMR (DMSO-d6, 300 MHz): δ 7.27 (d 1H), 6.84 (d, 1H), 5.52 (br. S, 2H), 1.74-1.83 (m, 1H), 0.92-0.98 (m, 2H), 0.62-0.73 (m, 2H); m/z=238.0 (M+MeCN+H)+.

Reference： [1]Current Patent Assignee: RIGEL PHARMACEUTICALS INC - US2011/130415, 2011, A1 Location in patent: Page/Page column 46
[2]Current Patent Assignee: RIGEL PHARMACEUTICALS INC - US2012/22092, 2012, A1 Location in patent: Page/Page column 31-32

13
[ 1104637-36-6 ]
[ 1309831-15-9 ]
[ 1309833-20-2 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate In water; toluene at 100℃; Inert atmosphere;	30 Example 30Synthesis of 1-(2-Cyclopropyl-4-fluoro-5-nitrophenyl)-4-methyl-1H-tetrazol-5(4H)-one1-(2-Bromo-4-fluoro-5-nitrophenyl)-4-methyl-1H-tetrazol-5(4H)-one (350 mg, 1.1 mmol) was added to toluene/water (4.6 mL:0.9 mL), in a 60 ml round bottom flask fitted with a water condenser. To this solution was added tricyclohexylphosphine (92 mg, 0.3 mmol), Cs2CO3 (2.14 g, 6.6 mmol) and cyclopropylboronic acid MIDA ester (303 mg, 1.5 mmol). This mixture was degassed by bubbling N2 into the solution for 15 minutes. Pd(OAc)2 (37 mg, 0.2 mmol) was added, and the mixture was heated to 100° C. under N2 and stirred overnight. After allowing to cool to room temperature, EtOAc and saturated K2CO3 were added, and the organic and aqueous layers were partitioned. The organic layer was dried (Na2SO4), filtered and the solvent was concentrated under vacuum to leave a crude residue. The residue was purified by column chromatography on silica gel using EtOAc/hexanes (1:3 to 1:2.5) as an eluent to give the title compound as a yellow solid (200 mg).1H NMR (300 MHz, DMSO) δ 8.37 (d, J=7.5 Hz, 1H), 7.32 (d, J=12.6 Hz, 1H), 3.61 (s, 3H), 1.87 (m, 1H), 1.08-1.04 (m, 2H), 0.97-0.93 (m, 2H); m/z=279.95 (M+H)+.

Reference： [1]Current Patent Assignee: RIGEL PHARMACEUTICALS INC - US2011/130415, 2011, A1 Location in patent: Page/Page column 46

14
[ 1104637-36-6 ]
[ 1309832-05-0 ]
[ 1309832-06-1 ]

Yield	Reaction Conditions	Operation in experiment
76%	With caesium carbonate In water; toluene at 100℃; Inert atmosphere;	116 Example 1161-(3-Cyclopropyl-2-fluoro-5-nitrophenyl)-4-methyl-1H-tetrazol-5(4H)-one1-(3-Bromo-2-fluoro-5-nitrophenyl)-4-methyl-1H-tetrazol-5(4H)-one (120 mg, 0.38 mmol) was added to toluene/water (1.5 ml:0.3 ml), in a carousel reaction tube. To this solution, tricyclohexylphosphine (35 mg, 0.11 mmol), cesium carbonate (750 mg, 2.3 mmol), cyclopropylboronic acid MIDA ester (104 mg, 0.53 mmol) were added subsequently. This mixture was degassed by bubbling N2 into the solution for 15 minutes, and finally palladium acetate (13 mg, 0.057 mmol) was added to the mixture and was heated at 100° C. with stirring under N2 overnight. The solution was cooled to room temperature. Ethyl acetate and saturated K2CO3 was added to the mixture, and the two layers were separated. Organic layer was dried with Na2SO4, after filtering off the solid, the mother liquor was concentrated under reduced pressure. The residue was purified with chromatography using ethyl acetate and hexanes (1:4) as an eluent to give the title compound (80 mg, 76% yield).1H NMR (300 MHz, DMSO) δ 8.4-8.38 (m, 1H), 7.99-7.96 (m, 1H), 3.62 (s, 3H), 2.21 (m, 1H), 1.12 (m, 2H), 0.96 (m, 2H).

Reference： [1]Current Patent Assignee: RIGEL PHARMACEUTICALS INC - US2011/130415, 2011, A1 Location in patent: Page/Page column 72

15
[ 1104637-36-6 ]
[ 1309832-49-2 ]
[ 1309832-50-5 ]

Yield	Reaction Conditions	Operation in experiment
90%	With caesium carbonate In water; toluene at 100℃; Inert atmosphere;	166 Example 1662-Cyclopropyl-3-fluoro-5-nitroanilineA mixture of 2-bromo-3-fluoro-5-nitroaniline (1.6 g, 6.81 mmol, 1 equiv), cyclopropylboronic acid MIDA ester (Aldrich; 4.0 g, 20.43 mmol, 3 equiv), Pd(OAc)2 (238 mg, 1.06 mmol, 0.15 equiv), Cy3P (578 mg, 2.06 mmol, 0.3 equiv) and Cs2CO3 (13.26 g, 40.8 mmol, 6 equiv) in toluene (70 mL) and H2O (14 mL) was de-gassed with N2 for 5 minutes. The mixture was then heated at 100° C. (oil bath temperature) overnight. After allowing to cool to room temperature, the mixture was diluted with EtOAc (100 mL) and H2O (50 mL) and the mixture filtered through Celite. The filter cake was washed with EtOAc (2×50 mL) and the filtrate partitioned. The organic layer was evaporated under vacuum to leave a crude residue which was purified by column chromatography on silica gel using EtOAc/hexanes (1:4) as eluent to give the product (1.2 g, 90%) as a dark yellow solid.1H NMR (CDCl3, 300 MHz): δ 7.29-7.21 (m, 2H), 4.44 (br. s, 2H), 1.52-1.42 (m, 1H), 1.11-1.05 (m, 2H), 0.73-0.67 (m, 2H); m/z=197.2 (M+H)+
90%	With caesium carbonate; tricyclohexylphosphine In water; toluene at 100℃; Inert atmosphere;	24 Synthesis of 2-cyclopropyl-3-fluoro-5-nitroaniline Example 24 Synthesis of 2-cyclopropyl-3-fluoro-5-nitroaniline A mixture of 2-bromo-3-fluoro-5-nitroaniline (1.6 g, 6.81 mmol, 1 equiv), cyclopropylboronic acid MIDA ester (Aldrich; 4.0 g, 20.43 mmol, 3 equiv), Pd(OAc)2 (238 mg, 1.06 mmol, 0.15 equiv), Cy3P (578 mg, 2.06 mmol, 0.3 equiv) and Cs2CO3 (13.26 g, 40.8 mmol, 6 equiv) in toluene (70 mL) and H2O (14 mL) was de-gassed with N2 for 5 minutes. The mixture was then heated at 100° C. (oil bath temperature) overnight. After allowing to cool to room temperature, the mixture was diluted with EtOAc (100 mL) and H2O (50 mL) and the mixture filtered through Celite. The filter cake was washed with EtOAc (2*50 mL) and the filtrate partitioned. The organic layer was evaporated under vacuum to leave a crude residue which was purified by column chromatography on silica gel using EtOAc/hexanes (1:4) as eluent to give the product (1.2 g, 90%) as a dark yellow solid. 1H NMR (CDCl3, 300 MHz): δ 7.29-7.21 (m, 2H), 4.44 (br. s, 2H), 1.52-1.42 (m, 1H), 1.11-1.05 (m, 2H), 0.73-0.67 (m, 2H); m/z=197 (M+H)+

Reference： [1]Current Patent Assignee: RIGEL PHARMACEUTICALS INC - US2011/130415, 2011, A1 Location in patent: Page/Page column 84
[2]Current Patent Assignee: RIGEL PHARMACEUTICALS INC - US2012/22092, 2012, A1 Location in patent: Page/Page column 37

16
[ 1104637-36-6 ]
[ 1309833-32-6 ]
[ 1356493-56-5 ]

Yield	Reaction Conditions	Operation in experiment
69%	With caesium carbonate; tricyclohexylphosphine In water; toluene at 100℃; Inert atmosphere;	31 Synthesis of 3-cyclopropyl-2-fluoro-5-nitroaniline Example 31 Synthesis of 3-cyclopropyl-2-fluoro-5-nitroaniline A mixture of 3-bromo-2-fluoro-5-nitroaniline (2.20 g, 9.36 mmol, 1 equiv), cyclopropylboronic acid MIDA ester (Aldrich; 11.07 g, 56.17 mmol, 6 equiv), Cy3P (1.05 g, 3.74 mmol, 0.4 equiv), Cs2CO3 (54.90 g, 168.50 mmol, 18 equiv) in toluene/H2O (5:1; 450 mL:90 mL) followed by Pd(OAc)2 (0.420 g, 1.87 mmol. 0.20 equiv) was de-gassed by sonnicating under vacuum for 10 minutes and back-filled with N2. The mixture was then heated at 100° C. overnight. After allowing to cool to room temperature, the mixture was concentrated to dryness. The residue was taken in DCM, and silica gel was added at this stage so that the residue was absorbed directly on to silica gel. After removing the solvent under vacuum, the crude product was purified by column chromatography on silica gel using DCM to give the product 3-cyclopropyl-2-fluoro-5-nitroaniline (1.27 g, 69%) as a yellow solid.1H NMR (DMSO d6, 300 MHz): δ 7.38-7.42 (m, 1H), 6.90 (dd, J=2.7, 5.7 Hz, 1H), 5.80 (br. s, 2H), 2.00-2.09 (m, 1H), 0.95-1.01 (m, 2H), 0.71-0.76 (m, 2H); LCMS (m/z): 197 (MH+).

Reference： [1]Current Patent Assignee: RIGEL PHARMACEUTICALS INC - US2012/22092, 2012, A1 Location in patent: Page/Page column 39

Yield	Reaction Conditions	Operation in experiment
	With 4-methylphenylboronic acid In tetrahydrofuran	Example 4 - Generality of Purification Platform To establish the generality of the novel purification platform, its capacity to purify a series of MIDA boronates representing a diverse range of structures, including aryl, heteroaryl, alkynyl, alkenyl, and alkyl derivatives, was tested. Briefly, mock crude reaction mixtures were prepared by mixing each MIDA boronate ( 1 equiv.) (Table 1) with tolyl- boronic acid ( 1 equiv.) and a palladium catalyst (0.1 equiv) in THF. Each of these mixtures was then subjected to fully-automated purification via the hybrid precipitation/catch-and- release platform described in detail herein. At the end of this process, all of these MIDA boronates were obtained in >90% purity as judged by NMR (see Figures 11-26), and the yields of recovered MIDA boronates were good to outstanding (Table 1).Table 1. Purification from mock crude reaction mixtures
	With 4-methylphenylboronic acid In tetrahydrofuran	18 Example 18Generality of Purification PlatformThe following example, while not specific to a PIDA-based system, describes procedures that, when used with a PIDA-based system, are reasonably expected to achieve similarly effective results.To establish the generality of the novel purification platform, its capacity to purify a series of MID A boronates representing a diverse range of structures, including aryl, heteroaryl, alkynyl, alkenyl, and alkyl derivatives, was tested. Briefly, mock crude reaction mixtures were prepared by mixing each MID A boronate (1 equiv.) (Table 4) with tolyl- boronic acid (1 equiv.) and a palladium catalyst (0.1 equiv) in THF. Each of these mixtures was then subjected to fully-automated purification via the hybrid precipitation/catch-and- release platform described in detail herein. At the end of this process, all of these MIDA boronates were obtained in >90% purity as judged by 1H NMR, and the yields of recovered MIDA boronates were good to outstanding (Table 4).Table 4. Purification from mock crude reaction mixtures.Details of the procedure are as follows.Pre-activation of the Catalyst Solution: Palladium(II) acetate (0.001875 mmol, 2.5 mol%) and SPhos (0.00375 mmol, 5 mol%) per purification to be run were combined in an 8 mL scintillation vial equipped with a PTFE-coated magnetic stir bar and placed under an argon atmosphere. THF was added to generate a 0.01 M catalyst stock solution (with respect to palladium(II) acetate), and it was stirred vigorously for 30 min at room temperature to generate an orange, yellow, or clear solution. After this activation process, 1 mL catalyst stock solution was added to the solution in the polypropylene cartridge containing the simulated reaction mixture.Preparation and Installation of Simulated Reaction Chamber: A new fritted 12 g Luknova polypropylene cartridge was charged with MIDA boronate (0.075 mmol, 1 eq), 4- methylbenzene boronic acid (0.075 mmol, 1 eq), and THF (10 mL). After addition of the pre-activated catalyst solution, the cartridge was installed into the Luer fittings in the reaction block of the automated synthesizer. Once all cartridges were in place, the automated purification routine was run using the computer interface. The samples were collected as THF solutions into tared 40 mL scintillation vials.Concentration, Azeotropic Drying, and Analysis of Recovered Materials from Purifications: The THF solutions were concentrated under reduced pressure on a rotary evaporator, then the residue was azeotroped with dichloromethane (3 x 5 mL) to remove residual solvents. These residues were then placed under vacuum for 12-36 hours, after which yield and purity were determined by comparison of 1H NMR in acetone-20 and delivers it to top of precipitation chamber. This process is repeated once for a total delivery of 13 mL solvent.Primary pump delivers two 10-mL plugs of dry nitrogen to the bottom of the precipitation chamber (bypassing the silica gel column) to dislodge stir bar. Step (D) is repeated.Steps (K)-(M) are repeated. Step (D) is repeated again.Steps (K)-(M) are repeated twice with Et20 instead of 1.5% (v/v) MeOH in Et20. Step (D) is repeated twice more to dry out silica gel column.Auxiliary pump is rinsed with 2 x 1 mL THF to wash away any residual MeOH. Wash THF is sent to waste.Auxiliary pump aspirates 6 mL THF and delivers slowly to bottom of precipitation chamber through silica gel column. This process is repeated once for a total of 12 mL THF.Primary pump aspirates 5 mL dry nitrogen and delivers it to bottom of precipitation chamber (bypassing the silica gel column) to agitate the suspension, thus promoting mixing chiral, non-racemic PIDA boronate dissolution. This process is done 40 times.THF solution of chiral, non-racemic PIDA boronate is aspirated by primary pump out of the bottom of the precipitation chamber (bypassing the silica gel column). Solution is delivered to the collection tube. Thisaspiration/delivery is repeated an additional 5 times to ensure full transfer. Auxiliary pump pushes residual THF in silica gel column into bottom of precipitation chamber as a rinse.Primary pump aspirates 5 mL dry nitrogen and delivers it to bottom of precipitation chamber (bypassing the silica gel column) to agitate the suspension, thus promoting mixing chiral, non-racemic PIDA boronate dissolution. This process is done 5 times.THF rinse is aspirated by primary pump out of bottom of the precipitation chamber (bypassing the silica gel column). Solution is delivered to the collection tube. The results from this study of a wide range of structurally diverse MIDA boronates demonstrates that the hybrid precipitation/catch-and-release purification strategy is remarkably general.

18
[ 1104637-36-6 ]
[ 1584139-89-8 ]
[ 1584139-90-1 ]

Yield	Reaction Conditions	Operation in experiment
65%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; dipotassium hydrogenphosphate In 1,4-dioxane; water at 85℃; for 20h; Inert atmosphere;	B3 Intermediate B3 To a stirred mixture oflntermediate B3A (2.00 g, 4.31 mmol), palladiumdichloride dppf (946 mg, 1.29 mmol), potassium phosphate dibasic (2.25 g, 12.9 mmol)and cyclopropylboronic acid methyliminodiacetic acid ester (1.70 g, 8.61 mmol) indioxane (12 mL) under nitrogen was added water (3 mL). The reaction mixture was heated at 85 oc for 20 h and cooled to room20 temperature. The mixture was diluted with EtOAc and filtered through a pad of silica geltopped by CELITE. This was further eluted with EtOAc. The filtrate was concentratedunder reduced pressure and purified by silica gel chromatography (DCM/acetone) to giveIntermediate B3 (1.20 g, 65%): HPLC: RT= 3.246 min (H20/MeOH with TFA,CHROMOLITH SpeedROD column 4.6 x 50 mm, gradient= 4 min, wavelength= 220 nm). MS(ES): m/z = 426.1 [M+H+]; 1H NMR (400MHz, DMSO-d6) 8 10.29 (s, 1H), 8.38(d, J=8.6 Hz, 1H), 7.57-7.32 (m, 10H), 7.30 (d, J=7.5 Hz, 1H), 7.20 (t, J=7.6 Hz, 1H),7.11 (d, J=7.3 Hz, 1H), 5.08 (s, 2H), 5.04 (d, J=8.4 Hz, 1H), 2.26-2.13 (m, 1H), 1.09-0.95(m, 2H), 0.87-0.78 (m, 1H), 0.61-0.52 (m, 1H).

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2014/47374, 2014, A1 Location in patent: Paragraph 00291; 00292

19
[ 1104637-36-6 ]
[ 1584715-42-3 ]
[ 1584715-89-8 ]
[ 1584715-91-2 ]

Yield	Reaction Conditions	Operation in experiment
1: 26% 2: 30%	Stage #1: cyclopropylboronic acid methyliminodiacetic acid ester; (2S,3R)-tert-butyl 3-((9-bromo-5-(4-chlorophenyl)-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)carbamoyl)-2-(cyclopropylmethyl)-6,6,6-trifluorohexanoate With potassium phosphate; palladium diacetate; tricyclohexylphosphine In water; toluene at 90 - 100℃; for 5h; Inert atmosphere; Stage #2: In methanol; carbon dioxide Supercritical conditions; liquid CO₂;	7F; 7G Preparation 7F and Preparation 7G: (2S,3R)-tert-Butyl3-((3S)-(5-(4-chlorophenyl)-9-cyclopropyl-2-oxo-2,3-dihydro-1H-benzo[ e] [1 ,4 ]diazepin-3-yl)carbamoyl)-2-( cyclopropylmethyl)-6,6,6-trifluorohexanoate and (2S,3R)-tert-Butyl 3-( (3R)-( 5-( 4-chlorophenyl)-9-cyclopropyl-2-oxo-2,3-dihydro-1H-benzo[ e ][ 1,4 ]diazepin-3-15 yl)carbamoyl)-2-( cyclopropylmethyl)-6,6,6-trifluorohexanoate A stirred solution of Preparation 7E (0.16 g, 0.238 mmol), cyclopropylboronicacid (0.041 g, 0.477 mmol), tripotassium phosphate (0.202 g, 0.954 mmol) andtricyclohexylphosphine (6.69 mg, 0.024 mmol) in toluene (0.3 mL) and water (0.100 mL)20 was degassed twice and heated to 90 °C. Palladium(II) acetate (6.96 mg, 0.031 mmol)was added, and the reaction mixture was heated at 100 oc for 3h. The reaction mixturewas cooled to room temperature and extracted three times with EtOAc. The combinedorganic layers were washed with brine, dried over Na2S04, filtered and concentrated.The crude material was purified by silica gel chromatography (hexanes/EtOAc) to give a25 mixture of starting material and product. A stirred solution of a portion of this material (0.09 g, 0.134 mmol),cyclopropylboronic acid (0.012 g, 0.134 mmol), tripotassiumphosphate (0.114 g, 0.537- mmol), tricyclohexylphosphine (3.76 mg, 0.013 mmol) in toluene (2.0 mL) and water(0.667 mL) was degassed twice and heated to 90 °C. Palladium(II) acetate (3.91 mg,0.017 mmol) was added and the reaction mixture was heated to 100 oc for 2h. Thereaction mixture was cooled to room temperature and was extracted with three times with5 EtOAc. The combined organic layers were washed with brine, dried over Na2S04,filtered and concentrated. The crude material was purified by silica gel chromatography(hexanes/EtOAc This material was purified by SFC (CHIRALPAK IA, 250 x 4.6 mm ID,5)lm, 75/25 C02/MeOH, 3 mL/min) to give Preparation 7G (0.04 g, 0.063 mmol, 26%10 yield) and Preparation 7F (0.045 g, 0.071 mmol, 30% yield). Preparation 7F (2nd peak from SFC): HPLC: RT= 3.064 min (H20/CH3CNwith TFA, BEH C18 2.5)lm, 2.1x50mm, gradient= 4 min, wavelength= 220 nm);MS(ES): m/z = 632 [M+H+]; Chiral HPLC: RT= 3.90 min (C02/MeOH, CHIRALPAKIA 5)lm, 4.6x250mm, gradient= 9 min, wavelength= 223 nm). Preparation 7G (1st peak from SFC): HPLC: RT= 3.064 min (H20/CH3CNwith TFA, BEH C18 2.5)lm, 2.1x50mm, gradient= 4 min, wavelength= 220 nm);MS(ES): m/z = 632 [M+H+]; Chiral HPLC: RT= 2.72 min (C02/MeOH, CHIRALPAKIA 5)lm, 4.6x250mm, gradient= 9 min, wavelength= 223 nm).

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2014/47374, 2014, A1 Location in patent: Paragraph 00316; 00317; 00318; 00319; 00320

20
[ 1104637-36-6 ]
2-chloro-6-(2,2-difluoroethoxy)pyridin-4-amine [ No CAS ]
2-cyclopropyl-6-(2,2-difluoroethoxy)pyridin-4-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate In 1,4-dioxane; water at 95℃; for 24h;	1.15 1.15. Intermediate 30: 2-cyclopropyl-6-(2,2-difluoroethoxy)pyridin-4-amine Pd(dppf)Cl2 (98 mg, 0.120 mmol, 0.1 equiv) is added to a degassed suspension of 2-chloro-6-(2,2-difluoroethoxy)pyridin-4-amine (250 mg, 1.20 mmol, 1.0 equiv), cyclopropylboronic acid MIDA ester (283.7 mg, 1.44 mmol, 1.2 equiv) and Cs2C03 (977 mg, 3.0 mmol, 2.5 equiv) in 1 ,4-dioxane/water (4/1 mL, 0.30 M). The resulting mixture is stirred at 95°C for 24 h. The mixture is diluted with DCM and water. The aqueous phase is extracted with DCM. The combined organic phase is filtered through a phase separator and concentrated under vacuum. The crude is purified by flash chromatography on silica gel (eluting with petroleum ether/EtOAc 4/1) to afford the desired compound. LCMS: MW (calcd): 214; m/z MW (obsd): 215 (M+H).

Reference： [1]Current Patent Assignee: GALAPAGOS - WO2017/148787, 2017, A1 Location in patent: Paragraph 0276

21
[ 1104637-36-6 ]
methyl 5'-bromo-[2,3'-bipyridine]-6-carboxylate [ No CAS ]
methyl 5'-cyclopropyl-[2,3'-bipyridine]-6-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate; palladium diacetate; tricyclohexylphosphine In water; toluene at 100 - 150℃; for 39.5h; Microwave irradiation;	14 methyl 5'-cyclopropyl-[2,3'-bipyridine]-6-carboxylate Example 14 methyl 5'-cyclopropyl-[2,3'-bipyridine]-6-carboxylate A toluene/H2O (3/0.3 mL) solution of methyl methyl 5'-bromo-[2,3'-bipyridine]-6-carboxylate (35.2 mg, 0.12 mmol), cyclopropylboronic acid MIDA ester (35.5 mg, 0.18 mmol), Pd(OAc)2 (1.3 mg, 0.006 mmol), tricyclohexylphosphine (3.4 mg, 0.012 mmol) and potassium phophosphate (89.2 mg, 0.42 mmol) was microwaved at 150° C. for 30 minutes, followed by another 39 hours at 100° C., after additional MIDA ester and catalysts, until reaction went to completion as monitored by LC-MS. Solvent was removed in vacuo, after silica gel chromatography, title compound was obtained as light yellow sticky solid: 1H NMR (300 MHz, Chloroform-d) δ 8.96 (d, J=2.1 Hz, 1H), 8.47 (d, J=2.2 Hz, 1H), 8.11 (dd, J=7.1, 1.7 Hz, 1H), 8.04 (ddd, J=2.2, 2.2, 0.5 Hz, 1H), 7.95 (dd, J=7.9, 7.1 Hz, 1H), 7.90 (dd, J=7.9, 1.7 Hz, 1H), 4.04 (s, 3H), 2.06-1.97 (m, 1H), 1.11-1.05 (m, 2H), 0.87-0.82 (m, 2H); LRMS (M+H) m/z 255.36.

Reference： [1]Current Patent Assignee: RIGEL PHARMACEUTICALS INC - US2018/111917, 2018, A1 Location in patent: Paragraph 0443-0444

22
[ 1104637-36-6 ]
6-chloro-3-(((S)-10-hydroxy-7-((R)-3-phenylmorpholine-4-carbonyl)-7-azaspiro[4.5]decan-10-yl)methyl)pyrimidin-4(3H)-one [ No CAS ]
6-cyclopropyl-3-(((S)-10-hydroxy-7-((R)-3-phenylmorpholine-4-carbonyl)-7-azaspiro[4.5]decan-10-yl)methyl)pyrimidin-4(3H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%	With palladium diacetate; tricyclohexylphosphine tetrafluoroborate In water; toluene at 100℃; for 1.75h; Inert atmosphere; Sealed tube;	222 General Procedure 5: Suzuki coupling General procedure: A reaction vial was charged with a mixture of the appropriate halide (1 equiv.), the organoboron reagent (1-3 equiv.), a Pd catalyst (0.05-0.1 equiv.) and an inorganic base (2-5 equiv.) in a mixture of water and 1 ,4-dioxane or toluene, as stated. The mixture was degassed by evacuating and refilling with N2 three times or by bubbling N2 through for 5-15 min, then the reaction tube was sealed. The reaction was heated under the indicated conditions for the indicated time and allowed to cool to rt. Water or saturated NH4CI(aq)was added and the resulting mixture was extracted using DCM (x 3). The combined organic extracts were dried (phase separator), concentrated under reduced pressure and the remaining residue was purified by flash chromatography to give the product.

Reference： [1]Current Patent Assignee: O DOWD COLIN; THE MCCLAY FOUNDATION - WO2020/115501, 2020, A1 Location in patent: Page/Page column 90; 241

23
[ 1104637-36-6 ]
tert-butyl (R)-4-((S)-10-((4-chloro-6-oxopyrimidin-1(6H)-yl)methyl)-10-hydroxy-7-azaspiro[4.5]decane-7-carbonyl)-3-phenylpiperazine-1-carboxylate [ No CAS ]
tert-butyl (R)-4-((S)-10-((4-cyclopropyl-6-oxopyrimidin-1-(6H)-yl)methyl)-10-hydroxy-7-azaspiro[4.5]decane-7-carbonyl)-3-phenylpiperazine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%	With palladium diacetate; tricyclohexylphosphine tetrafluoroborate In water; toluene at 100℃; for 6h; Sealed tube; Inert atmosphere;	292.1 Step 1: tert-Butyl (R)-4-((S)- 10-((4-cyclopropyl-6-oxopyrimidin- 1 (6H)-yl) methyl)- 10-hydroxy- 7-azaspiro[4.5]decane-7-carbonyI)-3-phenylpiperazine-1-carboxylate: A suspension of tert- butyl (R)-4-((S)-10-((4-chloro-6-oxopyrimidin-1(6H)-yl)methyl)-10-hydroxy-7- azaspiro[4.5]decane-7-carbonyl)-3-phenylpiperazine-1-carboxylate (15 mg, 0.026 mmol), cyclopropylboronic acid MIDA ester (10 mg, 0.051 mmol), tricyclohexylphosphonium tetrafluoro borate (2.8 mg, 0.0077 mmol) and Pd(OAc)2 (0.9 mg, 0.0038 mmol) in toluene (0.45 mL) and water (0.05 mL) in a sealed vial was 'degassed' by evacuating and backfilling the vessel with nitrogen. The reaction mixture was heated at 100 °C (sand bath) for 6 h. The volatiles were evaporated under reduced pressure and the residue was dry loaded onto silica and purified by flash chromatography (5-100% EtOAc in cyclohexane) to give the title compound (10 mg, 66%) as a white solid. LCMS (Method A): RT = 1.58 min, m/z = 592 [M+H]+.

Reference： [1]Current Patent Assignee: O DOWD COLIN; THE MCCLAY FOUNDATION - WO2020/115501, 2020, A1 Location in patent: Page/Page column 269

24
[ 1104637-36-6 ]
tert-butyl (R)-4-((S)-10-((4-chloro-2-oxopyridin-1(2H)-yl)methyl)-10-hydroxy-7-azaspiro[4.5]decane-7-carbonyl)-3-phenylpiperazine-1-carboxylate [ No CAS ]
tert-butyl (R)-4-((S)-10-((4-cyclopropyl-2-oxopyridin-1(2H)-yl)methyl)-10-hydroxy-7-azaspiro[4.5]decane-7-carbonyl)-3-phenylpiperazine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With palladium diacetate; tricyclohexylphosphine tetrafluoroborate In water; toluene at 100℃; for 17.58h; Inert atmosphere; Sealed tube;	327.1 General Procedure 5: Suzuki coupling General procedure: A reaction vial was charged with a mixture of the appropriate halide (1 equiv.), the organoboron reagent (1-3 equiv.), a Pd catalyst (0.05-0.1 equiv.) and an inorganic base (2-5 equiv.) in a mixture of water and 1 ,4-dioxane or toluene, as stated. The mixture was degassed by evacuating and refilling with N2 three times or by bubbling N2 through for 5-15 min, then the reaction tube was sealed. The reaction was heated under the indicated conditions for the indicated time and allowed to cool to rt. Water or saturated NH4CI(aq)was added and the resulting mixture was extracted using DCM (x 3). The combined organic extracts were dried (phase separator), concentrated under reduced pressure and the remaining residue was purified by flash chromatography to give the product.

Reference： [1]Current Patent Assignee: O DOWD COLIN; THE MCCLAY FOUNDATION - WO2020/115501, 2020, A1 Location in patent: Page/Page column 90; 300

25
[ 1104637-36-6 ]
(1S,2S,3R,4R)-3-((5-bromo-2-((3-(pyrrolidine-1-carbonyl)phenyl)amino)pyrimidin-4-yl)amino)bicyclo[2.2.1]hept-5-ene-2-carboxamide [ No CAS ]
(1S,2S,3R,4R)-3-((5-cyclopropyl-2-((3-(pyrrolidine-1-carbonyl)phenyl)amino)pyrimidin-4-yl)amino)bicyclo[2.2.1]hept-5-ene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
12%	With potassium dihydrogen orthophosphate; palladium diacetate; tricyclohexylphosphine In lithium hydroxide monohydrate; toluene at 120℃; for 5h;

Reference： [1]Chen, Yan; Lin, Nan; Masuda, Esteban S.; Payan, Donald G.; Singh, Rajinder; Taylor, Vanessa [ACS Medicinal Chemistry Letters, 2022, vol. 13, # 4, p. 714 - 719]

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	1104637-36-6	MDL No. :	MFCD11215247
Formula :	C₈H₁₂BNO₄	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	LLXFTRDFBQZFSN-UHFFFAOYSA-N
M.W :	197.00	Pubchem ID :	44138342
Synonyms :

Signal Word:	Warning	Class:	N/A
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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. 1104637-36-6 ] {[proInfo.proName]}

Quality Control of [ 1104637-36-6 ]

Related Doc. of [ 1104637-36-6 ]

Product Details of [ 1104637-36-6 ]

Safety of [ 1104637-36-6 ]

Application In Synthesis of [ 1104637-36-6 ]

[ 1104637-36-6 ] Synthesis Path-Upstream 1~2

[ 1104637-36-6 ] Synthesis Path-Downstream 1~25

Related Functional Groups of
[ 1104637-36-6 ]

Organoboron

Esters

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

[ CAS No. 1104637-36-6 ] {[proInfo.proName]}

Quality Control of [ 1104637-36-6 ]

Related Doc. of [ 1104637-36-6 ]

Product Details of [ 1104637-36-6 ]

Safety of [ 1104637-36-6 ]

Application In Synthesis of [ 1104637-36-6 ]

[ 1104637-36-6 ] Synthesis Path-Upstream 1~2

[ 1104637-36-6 ] Synthesis Path-Downstream 1~25

Related Functional Groups of [ 1104637-36-6 ]

Organoboron

Esters

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 1104637-36-6 ]