22237-12-3|3-Amino-4-methylphenylboronic Acid| Ambeed

CAS No. :	22237-12-3
Formula :	C₇H₁₀BNO₂
M.W :	150.97
SMILES Code :	CC1=CC=C(B(O)O)C=C1N
MDL No. :	MFCD01074640
InChI Key :	PLTGUDDQNWJILD-UHFFFAOYSA-N
Pubchem ID :	2737803

Safety of [ 22237-12-3 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H315-H319
Precautionary Statements:	P305+P351+P338

Application In Synthesis of [ 22237-12-3 ]

* 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.

Downstream synthetic route of [ 22237-12-3 ]

[ 22237-12-3 ] Synthesis Path-Downstream 1~54

1
[ 22237-12-3 ]
Tris-(3-hydroxy-4-methyl-phenyl)-cyclotriboroxan [ No CAS ]

References: [1]Journal of the American Chemical Society,1932,vol. 54,p. 4415,4418.

2
[ 80500-27-2 ]
[ 22237-12-3 ]

References: [1]Green Chemistry,2020,vol. 22,p. 1301 - 1307.
[2]Journal of the American Chemical Society,1932,vol. 54,p. 4415,4418.

3
[ 22237-12-3 ]
[ 108-24-7 ]
acetic acid-(5-dihydroxyboranyl-2-methyl-anilide) [ No CAS ]

References: [1]Journal of the American Chemical Society,1932,vol. 54,p. 4415,4418.

4
[ 22237-12-3 ]
[ 98-88-4 ]
benzoic acid-(5-dihydroxyboranyl-2-methyl-anilide) [ No CAS ]

References: [1]Journal of the American Chemical Society,1932,vol. 54,p. 4415,4418.

5
[ 5720-05-8 ]
[ 22237-12-3 ]

References: [1]Journal of the American Chemical Society,1932,vol. 54,p. 4415,4418.

6
[ 4294-57-9 ]
[ 22237-12-3 ]

References: [1]Journal of the American Chemical Society,1932,vol. 54,p. 4415,4418.

7
[ 317826-46-3 ]
[ 22237-12-3 ]
[ 317827-93-3 ]

Yield	Reaction Conditions	Operation in experiment
		2-[(S)-1-Phenylethylamino]-4-[5-(3-amino-4-methyl-phenyl)benzimidazol-1-yl]pyrimidine The title compound was prepared according to the procedure described in EXAMPLE 397, starting from 2-[(S)-1-Phenylethylamino]-4-[5-iodobenzimidazol-1-yl]pyrimidine and 3-amino-4-methyl-phenylboronic acid. Mass spectrum (ESI) 421.3 (M+1).

References: [1]Patent: US6498165,2002,B1 .

8
[ 110-71-4 ]
[ 275386-74-8 ]
4-methyl-3-nitrophenyl-boronic acid (TCl) [ No CAS ]
[ 22237-12-3 ]
[ 497-19-8 ]
(Z)-4-(3-Amino-4-methyl-phenyl)-1,3-dihydro-5-fluoro-3-[(4-methyl-1H-imidazol-5-yl)methylene]-2H-indol-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	(Ph3P)2PdCl2; In N,N-dimethyl-formamide;	Example 60 (Z)-4-(3-Amino-4-methyl-phenyl)-1,3-dihydro-5-fluoro-3-[(4-methyl-1H-imidazol-5-yl)methylene]-2H-indol-2-one (GGG) 3-Amino-4-methylphenylboronic acid was prepared by hydrogenation of 4-methyl-3-nitrophenyl-boronic acid (TCl). A solution of (Z)-1,3-dihydro-5-fluoro-4-iodo-3-[(4-methyl-1H-imidazol-5-yl)methylene]-2H-indol-2-one (50 mg, 0.135 mmol) (Starting Material 11), 2M aqueous Na2CO3 solution (0.14 mL), (Ph3P)2PdCl2 (11 mg, 0.0135 mmol) and 3-amino-4-methylphenylboronic acid (51.2 mg, 0.339 mmol) in a 1:4 mixture of DMF:1,2-dimethoxyethane (5 mL) was heated at 104 C. for 4 days. The reaction mixture was concentrated and the crude material was purified by C18 reverse phase chromatography to give (Z)-4-(3-Amino-4-methyl-phenyl)-1,3-dihydro-5-fluoro-3-[(4-methyl-1H-imidazol-5-yl)methylene]-2H-indol-2-one. (Yield 19 mg, 40%).

References: [1]Patent: US6307056,2001,B1 .

9
[ 50596-36-6 ]
[ 22237-12-3 ]
[ 1126369-28-5 ]

Yield	Reaction Conditions	Operation in experiment
92%		To 4-(pyridin-2-ylmethoxy)benzoic acid (300 mg, 1.31 mmol), HATU (522 mg, 1.37 mmol) and DIPEA (0.457 mL, 2.62 mmol) was added DMF (3 mL). After stirring for 1 h at 50 0C, the mixture was cooled and 3-amino-4-methylphenylboronic acid (198 mg, 1.31 mmol) was added. The reaction was reheated to 50 0C for 6 h , an additional equivalent of 3- amino-4-methylphenylboronic acid was added, and the reaction was stirred at RT for 48h. The reaction was poured into sat. NaCl solution (30 mL). The precipitate was filtered, washed with water, followed by Et2O, and dried under suction to yield the title compound (434 mg, 92 %). 1R NMR (DMSO-de) δ 9.75 (s, IH), 8.61 (d, IH), 7.96 (d, 2H), 7.90 (td, IH), 7.67 (s, IH), 7.58 (m, 2H), 7.40 (dd, IH), 7.22 (d, IH), 7.14 (d, 2H), 5.29 (s, 2H), 2.20 (s, 3H). MS (M+H+) = 363.
92%	With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20 - 50℃; for 65h;	To 4-(pyridin-2-ylmethoxy)benzoic acid (300 mg, 1.31 mmol), HATU (522 mg, 1.37 mmol) and DIPEA (0.457 mL, 2.62 mmol) was added DMF (3 mL). After stirring for 1 h at 50 C, the mixture was cooled and 3-amino-4-methylphenylboronic acid (198 mg, 1.31 mmol) was added. The reaction was reheated to 50 C for 6 h. As HOAt ester was still present, an additional equivalent of 3-amino-4-methylphenylboronic acid was added, and the reaction was stirred at RT for 48h. The reaction was poured into sat. NaCl solution (30 mL). The precipitate was filtered, washed with water, followed by Et2O, and dried under suction to yield the title compound (434 mg, 92 %). 1H NMR (DMSO-d6) δ ppm 9.75 (s, 1H), 8.61 (d, 1H), 7.96 (d, 2H), 7.90 (td, 1H), 7.67 (s, 1H), 7.58 (m, 2H), 7.40 (dd, 1H), 7.22 (d, 1H), 7.14 (d, 2H), 5.29 (s, 2H), 2.20 (s, 3H). LCMS (M+H) = 363.

References: [1]Patent: WO2009/27746,2009,A1 .Location in patent: Page/Page column 52.
[2]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 4907 - 4911.

10
[ 223102-72-5 ]
[ 22237-12-3 ]
[ 1126369-44-5 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 0 - 25℃; for 3h;	In a 100 mL round-bottomed flask was dissolved 4-(3-methoxybenzyloxy)benzoic acid (0.47 g, 1.82 mmol), 3-amino-4-methylphenylboronic acid (0.288 g, 1.91 mmol), and DIPEA (0.795 mL, 4.55 mmol) in DMF (2 mL) to give a brown solution. The reaction mixture was cooled to 0 0C before HATU (0.727 g, 1.91 mmol) was added. After the reaction mixture was warmed to RT, it was stirred for additional 3h. Water (50 mL) was added and filtration afforded the title compound as a brown solid. MS (M+H+) = 392.

References: [1]Patent: WO2009/27746,2009,A1 .Location in patent: Page/Page column 68.

11
[ 22237-12-3 ]
[ 16234-15-4 ]
[ 956390-23-1 ]

References: [1]Journal of Medicinal Chemistry,2008,vol. 51,p. 5522 - 5532.

12
[ 201230-82-2 ]
[ 1190766-99-4 ]
[ 22237-12-3 ]
[ 1263508-01-5 ]

Yield	Reaction Conditions	Operation in experiment
45%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; at 85℃; under 9000.9 Torr; for 24h;Autoclave; Inert atmosphere;	General procedure: The autoclave and the magnetic stirring bar were dried in an oven and then cool to room temperature under an argon atmosphere. Boronic acid (1.1 mmol), K2CO3 (5 mmol, flame dried prior to use) and Pd(PPh3)4 (0.05 mmol) were introduced then the autoclave was flushed with argon for 5 min. A degassed solution (argon bubbling for 10 min) of aniline 5 or 6 (1 mmol) in dry dioxane (10 mL) was added and the autoclave was flushed three times with CO and pressurized to 12 bar.After heating at 85 C in an oil bath for the appropriate time (24 h for adducts 3a-3e, 60 h for adducts 3f, 4a-4f, 9 and 10), the autoclave was cooled to room temperature and then cautionary discharged of the gas excess. Reaction mixture was diluted in ethyl acetate (10 mL) and washed with water (10 mL), saturated aqueous NH4Cl (10 mL) and brine (10 mL). The aqueous layers were combined, saturated with NaCl, acidified (by adding HCl 1 M until pH = 2) and extracted with ethyl acetate (2 × 20 mL). Organic layers were combined, dried over MgSO4, filtered and concentrated under reduce pressure. The crude residue was purified by flash chromatography and crystallized in the indicated solvents to give the attempted compounds.Caution: CO is a highly toxic odorless and colorless gas. Reactions involving Carbon Monoxide must be performed in a well-ventilated hood with a Carbon Monoxide detector nearby.

References: [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 95 - 100.

13
[ 201230-82-2 ]
[ 1263507-86-3 ]
[ 22237-12-3 ]
[ 1263508-13-9 ]

Yield	Reaction Conditions	Operation in experiment
54%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; at 85℃; under 9000.9 Torr; for 60h;Autoclave; Inert atmosphere;	General procedure: The autoclave and the magnetic stirring bar were dried in an oven and then cool to room temperature under an argon atmosphere. Boronic acid (1.1 mmol), K2CO3 (5 mmol, flame dried prior to use) and Pd(PPh3)4 (0.05 mmol) were introduced then the autoclave was flushed with argon for 5 min. A degassed solution (argon bubbling for 10 min) of aniline 5 or 6 (1 mmol) in dry dioxane (10 mL) was added and the autoclave was flushed three times with CO and pressurized to 12 bar.After heating at 85 C in an oil bath for the appropriate time (24 h for adducts 3a-3e, 60 h for adducts 3f, 4a-4f, 9 and 10), the autoclave was cooled to room temperature and then cautionary discharged of the gas excess. Reaction mixture was diluted in ethyl acetate (10 mL) and washed with water (10 mL), saturated aqueous NH4Cl (10 mL) and brine (10 mL). The aqueous layers were combined, saturated with NaCl, acidified (by adding HCl 1 M until pH = 2) and extracted with ethyl acetate (2 × 20 mL). Organic layers were combined, dried over MgSO4, filtered and concentrated under reduce pressure. The crude residue was purified by flash chromatography and crystallized in the indicated solvents to give the attempted compounds.Caution: CO is a highly toxic odorless and colorless gas. Reactions involving Carbon Monoxide must be performed in a well-ventilated hood with a Carbon Monoxide detector nearby.

References: [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 95 - 100.

14
[ 1019780-48-3 ]
[ 22237-12-3 ]
[ 1311148-75-0 ]