[ CAS No. 21440-97-1 ] {[proInfo.proName]}

Name: 21440-97-1|6-Bromo-4,4-dimethyl-1,4-dihydrobenzo[d][1,3]oxazin-2-one|98%
Brand: Ambeed
SKU: A412846
Rating: 97 (40 reviews)

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Product Details of [ 21440-97-1 ]

CAS No. :	21440-97-1	MDL No. :	MFCD00866701
Formula :	C₁₀H₁₀BrNO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	JRXGULDSFFLUAO-UHFFFAOYSA-N
M.W :	256.10	Pubchem ID :	30630
Synonyms :

Safety of [ 21440-97-1 ]

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 [ 21440-97-1 ]

* 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 [ 21440-97-1 ]
Downstream synthetic route of [ 21440-97-1 ]

[ 21440-97-1 ] Synthesis Path-Upstream 1~6

1
[ 530-62-1 ]
[ 304853-89-2 ]
[ 21440-97-1 ]

Yield	Reaction Conditions	Operation in experiment
100%	at 50℃;	Step 2: 6-Bromo-4,4-dimethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one; This compound was prepared as described in U.S. Pat. No. 6,444,668. To a solution of 2-(2-amino-5-bromo-phenyl)-propan-2-ol (18 g, 78 mmol), prepared in the previous step, in dry THF (150 mL) was added 1,1'-carbonyldiimidazole (15.5 g, 94 mmol) under nitrogen. The reaction was heated at 50° C. overnight. The solvent was removed under reduced pressure and the residue was dissolved in ethyl acetate (100 mL). The solution was washed with 1 N HCl (2.x.40 mL), brine (20 mL), dried over anhydrous MgSO₄and filtered. After removal of the solvent under reduced pressure 6-bromo-4,4-dimethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one (20 g, 100percent) was obtained as a white solid, mp 199-200° C.

Reference： [1] Journal of Medicinal Chemistry, 2002, vol. 45, # 20, p. 4379 - 4382
[2] Patent: US2002/49204, 2002, A1,
[3] Patent: US2002/68735, 2002, A1,
[4] Patent: US6436929, 2002, B1,
[5] Patent: US6444668, 2002, B1,
[6] Patent: US2009/197878, 2009, A1, . Location in patent: Page/Page column 11
[7] Journal of Medicinal Chemistry, 2005, vol. 48, # 16, p. 5092 - 5095

2
[ 135484-83-2 ]
[ 75-16-1 ]
[ 21440-97-1 ]

Yield	Reaction Conditions	Operation in experiment
72.8%	Stage #1: at 0 - 20℃; for 7 h; Inert atmosphere Stage #2: With 1,1'-carbonyldiimidazole In tetrahydrofuran for 3 h; Inert atmosphere	Add 50g compound 16 to the 1L three-neck bottleThen add 500ml THF,Replace the air in the reaction flask with nitrogen,The reaction system is cooled to 0 ° C,Slowly add 160 ml of MeMgBr (3M in THF) under nitrogen protection.After maintaining the temperature for 1 h, the reaction was stirred for 6 h after warming to room temperature.38.8 g of N,N'-carbonyldiimidazole (CDI) was added to monitor the complete reaction of the starting materials.Continue to stir for 3h,The reaction was then quenched by the addition of saturated NH4Cl solution.The solution was separated and the aqueous phase was extracted twice with dichloromethane, 100 ml each time.The organic phase is combined and washed once with saturated brine.Dry anhydrous Na2SO4 for 1 h, remove the desiccant by filtration,After the filtrate was concentrated, the target product compound 17 was obtained as a white solid 40.5 g.The yield was 72.8percent.

Reference： [1] Patent: CN108912138, 2018, A, . Location in patent: Paragraph 0153-0155

3
[ 21440-96-0 ]
[ 21440-97-1 ]

Reference： [1] Patent: WO2018/17490, 2018, A1, . Location in patent: Paragraph 0167; 0168

4
[ 52727-57-8 ]
[ 21440-97-1 ]

Reference： [1] Journal of Medicinal Chemistry, 2005, vol. 48, # 16, p. 5092 - 5095

5
[ 551-93-9 ]
[ 21440-97-1 ]

Reference： [1] Patent: WO2018/17490, 2018, A1,

6
[ 15833-00-8 ]
[ 21440-97-1 ]

Reference： [1] Patent: WO2018/17490, 2018, A1,

[ 21440-97-1 ] Synthesis Path-Downstream 1~82

2
[ 68-12-2 ]
[ 21440-97-1 ]
[ 899438-41-6 ]

Yield	Reaction Conditions	Operation in experiment
62%		To a tetrahydrofuran (5mL) solution of <strong>[21440-97-1]6-bromo-4,4-dimethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one</strong> (173mg, 0.676 mmol), 1.58M n-butyllithium-hexane solution (1.4mL, 2.2 mmol) was added dropwise at -70C and stirred for 30 minutes. After that, N,N-dimethylformamide (0.20mL, 2.6 mmol) was added dropwise and the mixture was warmed to 20-25C and stirred for 2 hours. The reaction liquid was poured into water and extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and the obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate = 2/1 - 1/1) to give 4,4-dimethyl-2-oxo-1,4-dihydro-2H-3,1-benzoxazin-6-carbaldehyde (86.3mg, 62%). 1H-NMR (CDCl3) delta :1.78(6H,s), 6.98(1H,d,J=8.0Hz), 7.72(1H,s), 7.79(1H,dd, J=8.4, 2.0Hz), 9.91 (1H,s)

Reference： [1]Patent: EP1844768,2007,A1 .Location in patent: Page/Page column 26
[2]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 2185 - 2189

3
[ 138900-55-7 ]
[ 21440-97-1 ]
[ 709028-06-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 2185 - 2189

4
[ 21440-97-1 ]
[ 135884-31-0 ]
[ 304853-96-1 ]

Yield	Reaction Conditions	Operation in experiment
62%	With potassium carbonate;tetrakis(triphenylphosphine)palladium (0); In ethanol; water; toluene;	EXAMPLE 94 2-(4,4-Dimethyl-2-oxo-1,4-dihydro-2H-benzo[d] [1,3]oxazin-6-yl)-pyrrole-1-carboxylic acid tert-butyl ester A solution of 6-bromo-4,4-dimethyl-1,4-dihydro-benzo[d] [1,3]oxazin-2-one (0.87 g, 3.4 mmol) and tetrakis(triphenylphosphine)palladium(0) (96 mg, 0.08 mmol) in toluene (40 mL) was stirred under a flow of nitrogen for 25 min. To the solution was added sequentially 1-t-butoxycarbonylpyrrole-2-boronic acid (1.4 g, 7.0 mmol) in absolute ethanol (10 mL) and potassium carbonate (0.94 g, 7.0 mmol) in water (10 mL). The mixture was heated at 80 C. for 16 h and allowed to cool to rt. The reaction mixture was poured into aqueous saturated sodium bicarbonate solution (100 mL) and extracted with ethyl acetate (3*100 mL). The organic layers were combined, washed with water (100 mL) and brine (50 mL) and dried over magnesium sulfate. The solution was filtered, concentrated in vacuo, and the residue was purified by flash column chromatography on silica gel (30% ethyl acetate/hexane) to give the title compound as an off-white powder (0.7 g, 62%): mp 176 C. 1H NMR (CDCl3) delta1.40 (s, 9H), 1.73 (s, 6H), 6.17 (dd, 1H, J=1.8, 3.3 Hz), 6.22 (dd, 1H, J=3.3, 3.3 Hz), 6.77 (d, 1H, J=8.1 Hz), 7.13 (d, 1H, J=1.8 Hz), 7.23 (dd, 1H, J=1.8, 8.1 Hz), 7.33 (dd, 1H, J=1.8, 3.3 Hz), 7.69 (bs, 1H). MS ((-) ESI) m/z 341 [M-H]-. Anal. Calcd for C19H22N2O4: C, 66.65; H, 6.48; N, 8.18. Found: C, 65.46; H, 6.51; N, 7.74.
58%	With potassium carbonate;tetrakis(triphenylphosphine)palladium (0); In ethanol; water; toluene;	A solution of 6-bromo-4,4-dimethyl-1,4-dihydro-benzo [d][1,3]oxazin-2-one (5.0 g, 20 mmol) and tetrakis(triphenylphosphine)palladium(0) (580 mg, 0.5 mmol) in toluene (200 mL) was stirred under a flow of nitrogen for 25 min. To the solution was added sequentially 1-tert-butoxycarbonylpyrrole-2-boronic acid (8.24 g, 39 mmol) in absolute ethanol (50 mL) and potassium carbonate (5.39 g, 39 mmol) in water (50 mL). The mixture was heated to 80 C. for 16 h and allowed to cool. The reaction mixture was poured into aqueous saturated sodium bicarbonate solution (200 mL) and extracted with ethyl acetate (3*200 mL). The organic layers were combined, washed with water (200 mL) and brine (100 mL) and dried over magnesium sulfate. The solution was filtered, concentrated in vacuo, and the residue was purified by flash column chromatography on silica gel (30% ethyl acetate/hexane) to give 2-(4,4-dimethyl-2-oxo-1,4-dihydro-2H-benzo [d] [1,3] oxazin-6-yl)-pyrrole-1-carboxylic acid tert-butyl ester (4.0 g, 58%) as a tan solid, mp 172-173 C.
58%	With potassium carbonate;tetrakis(triphenylphosphine)palladium (0); In ethanol; water; toluene;	EXAMPLE 17 tert-Butyl 2-cyano-5-(4,4-dimethyl-2-thioxo-1,4-dihydro-2H-3,1-benzoxazin-6-yl)-1H-pyrrole-1-carboxylate A solution of <strong>[21440-97-1]6-bromo-4,4-dimethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one</strong> (5.0 g, 20 mmol) and tetrakis(triphenylphosphine)palladium(0) (580 mg, 0.5 mmol) in toluene (200 mL) was stirred under a flow of nitrogen for 25 min. To the solution was added sequentially 1-tert-butoxycarbonylpyrrole-2-boronic acid (8.24 g, 39 mmol) in absolute ethanol (50 mL) and potassium carbonate (5.39 g, 39 mmol) in water (50 mL). The mixture was heated to 80 C. for 16 h and allowed to cool. The reaction mixture was poured into an aqueous saturated sodium bicarbonate solution (200 mL) and extracted with ethyl acetate (3*200 mL). The organic layers were combined, washed with water (200 mL) and brine (100 mL) and dried over magnesium sulfate. The solution was filtered, concentrated in vacuo, and the residue was purified by flash column chromatography on silica gel (30% ethyl acetate/hexane) to give 2-(4,4-dimethyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yl)-pyrrole-1-carboxylic acid tert-butyl ester (4.0 g, 58%) as a tan solid, mp 172-173 C.

Reference： [1]Patent: US2002/49204,2002,A1
[2]Journal of Medicinal Chemistry,2005,vol. 48,p. 5092 - 5095
[3]Patent: US2002/68735,2002,A1
[4]Patent: US6436929,2002,B1
[5]RSC Advances,2016,vol. 6,p. 57569 - 57579
[6]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 2185 - 2189

5
[ 530-62-1 ]
[ 304853-89-2 ]
[ 21440-97-1 ]

Yield	Reaction Conditions	Operation in experiment
100%	In tetrahydrofuran; ethyl acetate;	EXAMPLE 2 6-Bromo-4,4-dimethyl-1,4-dihydro-benzo[d] [1,3]oxazin-2-one To a solution of 2-(2-amino-5-bromophenyl)propan-2-ol (18 g, 78 mmol) in dry THF (150 mL) was added 1,1'-carbonyldiimidazole (15.5 g, 94 mmol) under nitrogen. The reaction solution was heated at 50 C. overnight. The solvent was removed in vacuo and the residue was dissolved in ethyl acetate (100 mL). The solution was washed with 1N aqueous hydrochloride solution (2*40 mL), brine (20 mL), and dried with MgSO4. After removal of solvent in vacuo, 6-bromo-4,4-dimethyl-1,4-dihydro-benzo[d] [1,3]oxazin-2-one was obtained as a white solid (20 g, 100%): mp 199-200 C.; 1H-NMR (DMSO-d6) delta10.32 (s, 1H, D2O exchangeable), 7.48 (d, 1H, J=2.1 Hz), 7.43 (dd, 1H, J=8.5, 2.1 Hz), 6.84 (d, 1H, J=8.4 Hz), 161 (s, 6H).
100%	In tetrahydrofuran; ethyl acetate;	To a solution of 2-(2-amino-5-bromophenyl)propan-2-ol (18 g, 78 mmol) in dry THF (150 mL) was added 1,1'-carbonyldiimidazole (15.5 g, 94 mmol) under nitrogen. The reaction solution was heated at 50 C. overnight. The solvent was removed in vacuo and the residue was dissolved in ethyl acetate (100 mL). The solution was washed with 1N aqueous hydrochloride solution (2*40 mL), brine (20 mL), and dried with MgSO4. After removal of the solvent in vacuo, 6-bromo-4,4-dimethyl-1,4-dihydro-benzo [d][1,3]oxazin-2-one was obtained as a white solid (20 g, 100%): mp 199-200 C.; 1H-NMR (DMSO-d6) delta 10.32 (s, 1H, D2O exchangeable), 7.48 (d, 1H, J=2.1 Hz), 7.43 (dd, 1H, J=8.5, 2.1 Hz), 6.84 (d, 1H, J=8.4 Hz), 1.61 (s, 6H).
100%	In tetrahydrofuran; ethyl acetate;	EXAMPLE 2 6-Bromo-4,4-dimethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one To a solution of 2-(2-amino-5-bromophenyl)propan-2-ol (18 g, 78 mmol) in dry THF (150 mL) was added 1,1'-carbonyldiimidazole (15.5 g, 94 mmol) under nitrogen. The reaction solution was heated at 50 C. overnight. The solvent was removed in vacuo and the residue was dissolved in ethyl acetate (100 mL). The solution was washed with 1N aqueous hydrochloride solution (2*40 mL), brine (20 mL), and dried with MgSO4. After removal of solvent in vacuo, 6-bromo-4,4-dimethyl-1,4-dihydro-benzo[d][1,3]-oxazin-2-one was obtained as a white solid (20 g, 100%): mp 199-200 C.; 1H-NMR (DMSO-d6) delta10.32 (s, 1H, D2O exchangeable), 7.48 (d, 1H, J=2.1 Hz), 7.43 (dd, 1H, J=8.5, 2.1 Hz), 6.84 (d, 1H, J=8.4 Hz), 1.61 (s, 6H).

100%	In tetrahydrofuran; ethyl acetate;	EXAMPLE 2 6-Bromo-4,4-dimethyl-1,4-dihydro-benzo [d][1,3]oxazin-2-one To a solution of 2-(2-amino-5-bromophenyl)propan-2-ol (18 g, 78 mmol) in dry THF (150 mL) was added 1,1'-carbonyldiimidazole (15.5 g, 94 mmol) under nitrogen. The reaction solution was heated at 50 C. overnight. The solvent was removed in vacuo and the residue was dissolved in ethyl acetate (100 mL). The solution was washed with 1N aqueous hydrochloride solution (2*40 mL), brine (20 mL), and dried with MgSO4. After removal of solvent in vacuo, 6-bromo-4,4-dimethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one was obtained as a white solid (20 g, 100%): mp 199-200 C.; 1H-NMR (DMSO-d6) delta10.32 (s, 1H, D2O exchangeable), 7.48 (d, 1H, J=2.1 Hz), 7.43 (dd, 1H, J=8.5, 2.1 Hz), 6.84 (d, 1H, J=8.4Hz), 1.61 (s, 6H).
100%	In tetrahydrofuran; at 50℃;	Step 2: 6-Bromo-4,4-dimethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one; This compound was prepared as described in U.S. Pat. No. 6,444,668. To a solution of 2-(2-amino-5-bromo-phenyl)-propan-2-ol (18 g, 78 mmol), prepared in the previous step, in dry THF (150 mL) was added 1,1'-carbonyldiimidazole (15.5 g, 94 mmol) under nitrogen. The reaction was heated at 50 C. overnight. The solvent was removed under reduced pressure and the residue was dissolved in ethyl acetate (100 mL). The solution was washed with 1 N HCl (2×40 mL), brine (20 mL), dried over anhydrous MgSO4 and filtered. After removal of the solvent under reduced pressure 6-bromo-4,4-dimethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one (20 g, 100%) was obtained as a white solid, mp 199-200 C.

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 4379 - 4382
[2]Patent: US2002/49204,2002,A1
[3]Patent: US2002/68735,2002,A1
[4]Patent: US6436929,2002,B1
[5]Patent: US6444668,2002,B1
[6]Patent: US2009/197878,2009,A1 .Location in patent: Page/Page column 11
[7]Journal of Medicinal Chemistry,2005,vol. 48,p. 5092 - 5095

6
[ 5419-55-6 ]
[ 21440-97-1 ]
[ 304853-90-5 ]

Yield	Reaction Conditions	Operation in experiment
81%	With n-butyllithium; In tetrahydrofuran; hexane; ethyl acetate;	EXAMPLE 4 (1,4-Dihydro-4,4-dimethyl-2-oxo-2H-3,1-benzoxazin-6-yl)boronic acid To a solution of 6-bromo-4,4-dimethyl-1,4-dihydro-benzo[d] [1,3]oxazin-2-one (2 g, 7.8 mmol) in anhydrous THF (60 mL) was added a solution of n-BuLi in hexane (10 M, 2.4 mL, 24 mmol) at -78 C. under nitrogen. After stirring at -78 C. for 30 minutes, a slurry was obtained and treated with triisopropyl borate (6.5 mL, 28 mmol). The reaction medium was slowly warmed to ambient temperature and quenched with 1N aqueous hydrochloric acid solution (60 mL). Ethyl acetate (100 mL) was added and organic layer was separated, and aqueous layer was extracted with ethyl acetate (3*60 mL). The combined organic layer was washed with brine and dried with MgSO4. The solvent was removed in vacuo and the residue was purified by a silica gel flash chromatography (ethyl acetate:hexane/2: 1) to afford (1,4-dihydro-4,4-dimethyl-2-oxo-2H-3,1-benzoxazin-6-yl)boronic acid as a white solid (1.4 g, 81%): mp 249-250 C.; 1H-NMR (DMSO-d6) delta10.21 (s, 1H, D2O exchangeable), 7.90-7.95 (br s, 2H, D2O exchangeable), 7.67 (m, 2H), 6.79 (d, 1H, J=7.8 Hz), 161 (s, 6H); MS (ESI) m/z 222 ([M+H]+, 87%).
81%	With n-butyllithium; In tetrahydrofuran; hexane; ethyl acetate;	EXAMPLE 3 (1,4-Dihydro-4,4-dimethyl-2-oxo-2H-3,1-benzoxazin-6-yl)boronic acid To a solution of <strong>[21440-97-1]6-bromo-4,4-dimethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one</strong> (2 g, 7.8 mmol) in anhydrous THF (60 mL),was added a solution of n-BuLi in hexane (10 M, 2.4 mL, 24 mmol) at -78 C. under nitrogen. After stirring at -78 C. for 30 minutes, a slurry was obtained and treated with triisopropyl borate (6.5 mL, 28 mmol). The reaction solution was slowly warmed to ambient temperature and quenched with 1N aqueous hydrochloric acid solution (60 mL). Ethyl acetate (100 mL) was added, the organic layer was separated, and the aqueous layer was extracted with ethyl acetate (3*60 mL). The combined organic layer was washed with brine and dried with MgSO4. The solvent was removed in vacuo and the residue was purified by a silica gel flash chromatography (ethyl acetate:hexane/2:1) to afford (1,4-dihydro-4,4-dimethyl-2-oxo-2H-3,1-benzoxazin-6-yl)boronic acid as a white solid (1.4 g, 81%): mp 249-250 C.; 1H-NMR (DMSO-d6) delta10.21 (s, 1H, D2O exchangeable), 7.90-7.95 (br s, 2H, D2O exchangeable), 7.67 (m, 2H), 6.79 (d, 1H, J=7.8 Hz), 1.61 (s, 6H); MS (ESI) m/z 222([M+H]+, 87%).
81%	With n-butyllithium; In tetrahydrofuran; hexane; ethyl acetate;	EXAMPLE 4 (1,4-Dihydro-4,4-dimethyl-2-oxo-2H-3,1-benzoxazin-6-yl)boronic acid To a solution of <strong>[21440-97-1]6-bromo-4,4-dimethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one</strong> (2 g, 7.8 mmol) in anhydrous THF (60 mL) was added a solution of n-BuLi in hexane (10 M, 2.4 mL, 24 mmol) at -78 C. under nitrogen. After stirring at -78 C. for 30 minutes, a slurry was obtained and treated with triisopropyl borate (6.5 mL, 28 mmol). The reaction medium was slowly warmed to ambient temperature and quenched with 1N aqueous hydrochloric acid solution (60 mL). Ethyl acetate (100 mL) was added and organic layer was separated, and aqueous layer was extracted with ethyl acetate (3*60 mL). The combined organic layer was washed with brine and dried with MgSO4. The solvent was removed in vacuo and the residue was purified by a silica gel flash chromatography (ethyl acetate:hexane/2:1) to afford (1,4-dihydro-4,4-dimethyl-2-oxo-2H-3,1-benzoxazin-6-yl)boronic acid as a white solid (1.4 g, 81%): mp 249-250 C.; 1H-NMR (DMSO-d6) delta10.21 (s, 1H, D2O exchangeable), 7.90-7.95 (br s, 2H, D2O exchangeable), 7.67 (m, 2H), 6.79 (d, 1H, J=7.8 Hz), 1.61 (s, 6H); MS (ESI) m/z 222 ([M+H]+, 87%).

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 4379 - 4382
[2]Patent: US2002/49204,2002,A1
[3]Patent: US6436929,2002,B1
[4]Patent: US6444668,2002,B1

7
[ 1073-06-9 ]
[ 21440-97-1 ]
[ 304854-26-0 ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 4379 - 4382

8
[ 10365-98-7 ]
[ 21440-97-1 ]
[ 304854-36-2 ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 6 6-(3-Methoxy-phenyl)4,4-dimethyl-1,4-dihydro-benzo [d] [1,3]-oxazin-2one Prepared according to Procedure A from <strong>[21440-97-1]6-bromo-4,4-dimethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one</strong> and 3-methoxyphenyl boronic acid. Yellow solid: mp 164-165 C.; 1H-NMR (DMSO-d6) delta10.3 (s, 1H), 7.56 (m, 2H), 7.36 (t, 1H, J=7.89 Hz), 7.20 (m, 2H), 6.96 (d, 1H, J=8.88 Hz), 6.91 (dd, 1H, J=8.13, 2.35 Hz), 3.8 (s, 3H), 1.7 (s, 6H); MS (ESI) m/z 284 ([M+H]+, 30%); Anal. Calc. For C17H17NO3: C, 72.07, H, 6.05, N, 4.94. Found: C, 70.58, H, 5.73, N, 4.67
		EXAMPLE 6 6-(3-Methoxy-phenyl)-4,4dimethyl-1,4-dihydro-benzo[d][1,3]-oxazin-2-one Prepared according to Procedure A from <strong>[21440-97-1]6-bromo-4,4-dimethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one</strong> and 3-methoxyphenyl boronic acid. Yellow solid: mp 164-165 C.; 1H-NMR (DMSO-d6) delta10.3 (s, 1H), 7.56 (m, 2H), 7.36 (t, 1 H, J=7.89 Hz), 7.20 (m, 2H), 6.96 (d, 1H, J=8.88 Hz), 6.91 (dd, 1H, J=8.13, 2.35Hz), 3.8 (s, 3H), 1.7 (s, 6H); MS (ESI) m/z 284 ([M+H]+, 30 %); Anal. Calc. For C17H17NO3: C, 72.07, H, 6.05, N, 4.94. Found: C, 70.58, H, 5.73, N, 4.67

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 4379 - 4382
[2]Patent: US2002/49204,2002,A1
[3]Patent: US6444668,2002,B1

9
[ 63503-60-6 ]
[ 21440-97-1 ]
[ 304853-28-9 ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 4379 - 4382

10
[ 1679-18-1 ]
[ 21440-97-1 ]
6-(4-Chloro-phenyl)-4,4-dimethyl-1,4-dihydro-benzo [d] [1,3]-oxazin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 8 6-(4-Chloro-phenyl)-4,4-dimethyl-1,4-dihydro-benzo [d] [1,3]-oxazin-2-one Prepared according to Procedure A from <strong>[21440-97-1]6-bromo-4,4-dimethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one</strong> and 4-chlorophenyl boronic acid. White solid: mp 255-257 C.; 1H-NMR (DMSO-d6) delta10.3 (s, 1H), 7.7 (d, 2H, J=8.52 Hz), 7.55 (m, 2H), 7.5 (d, 2H, J=8.52 Hz), 6.96 (d, 1H, J=8.52 Hz), 1.7 (s, 6H); MS (ESI) m/z 288 ([M+H]+, 70%); Anal. Calc. For C16H14ClNO2: C, 66.79, H, 4.90, N, 4.87. Found: C, 66.34, H, 4.76, N, 4.75
		EXAMPLE 8 6-(4-Chloro-phenyl)-4,4-dimethyl-1,4-dihydro-benzo[d][1,3]-oxazin-2-one Prepared according to Procedure A from 6-bromo-4,4-dimethyl -1,4-dihydro-benzo[d][1,3]oxazin-2-one and 4- chlorophenyl boronic acid. White solid: mp 255-257 C.; 1H-NMR (DMSO-d6) delta10.3 (s, 1H), 7.7 (d, 2H, J=8.52 Hz), 7.55 (m, 2H), 7.5 (d, 2H, J=8.52 Hz), 6.96 (d, 1H, J=8.52 Hz), 1.7 (s, 6H); MS (ESI) m/z 288 ([M+H]+, 70%); Anal. Calc. For C16H14CINO2: C, 66.79, H, 4.90, N, 4.87. Found: C, 66.34, H, 4.76, N, 4.75

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 4379 - 4382
[2]Patent: US2002/49204,2002,A1
[3]Patent: US6444668,2002,B1

11
[ 3900-89-8 ]
[ 21440-97-1 ]
[ 304854-37-3 ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 7 6-(2-Chloro-phenyl)4,4-dimethyl-1,4-dihydro-benzo [d] [1,3] oxazin-2-one Prepared according to Procedure A from <strong>[21440-97-1]6-bromo-4,4-dimethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one</strong> and 2-chlorophenyl boronic acid. White solid: mp 181-182 C.; MS (ESI) m/z 288 ([M+H]+, 70%); Anal. Calc. For C16H14CINO2: C, 66.79 H, 4.90, N, 4.87. Found: C, 66.78, H, 4.82, N, 4.55
		EXAMPLE 7 6-(2-Chloro-phenyl)-4,4-dimethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one Prepared according to Procedure A from <strong>[21440-97-1]6-bromo-4,4-dimethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one</strong> and 2-chlorophenyl boronic acid. White solid: mp 181-182 C.; MS (ESI) m/z 288 ([M+H]+, 70%); Anal. Calc. For C16H14CINO2: C, 66.79, H, 4.90, N, 4.87. Found: C, 66.78, H, 4.82, N, 4.55

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 4379 - 4382
[2]Patent: US2002/49204,2002,A1
[3]Patent: US6444668,2002,B1

12
[ 21440-97-1 ]
6-bromo-4,4-dimethyl-benzoxazine-2-one sodium salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With sodium t-butanolate; In tetrahydrofuran; at 20℃;	Example 5 Preparation of 6-bromo-4,4-dimethyl-benzoxazine-2-one Sodium Salt 6-Bromo-4,4-dimethyl-benzoxazine-2-one (2.59 g) was dissolved in THF (50 mL) at ambient temperature followed by addition of sodium tert-butoxide (0.96 g). The mixture was gently heated until a solution was obtained. The solution was evaporated to give a white solid (2.86 g; quant. yield) that was soluble in N-methylpyrrolidone (NMP) and dimethyl pyrimidone (DMPU) heated to about 40 to about 50 C. 1H-NMR (DMSO-d6) did not show a peak corresponding to a N-H group.

Reference： [1]Patent: US2005/250766,2005,A1 .Location in patent: Page/Page column 10

13
[ 21440-97-1 ]
6-bromo-4,4-dimethyl-benzoxazine-2-one lithium salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With lithium tert-butoxide; In tetrahydrofuran;	Example 6 Preparation of 6-bromo-4,4-dimethyl-benzoxazine-2-one Lithium Salt Similarly, 6-bromo-4,4-dimethyl-benzoxazine-2-one (2.55 g) was reacted with lithium tert-butoxide (10 mL of 1M solution in THF). After evaporation a brownish solid was obtained (3.35 g; quant. yield) that was soluble in dimethyl pyrimidone (DMPU) without heating. 1H NMR (DMSO-d6) did not show a peak corresponding to a N-H group.

Reference： [1]Patent: US2005/250766,2005,A1 .Location in patent: Page/Page column 10

14
[ 21440-97-1 ]
[ 305796-34-3 ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 5092 - 5095

15
[ 21440-97-1 ]
[ 304853-97-2 ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 5092 - 5095
[2]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 2185 - 2189
[3]RSC Advances,2016,vol. 6,p. 57569 - 57579

16
[ 52727-57-8 ]
[ 21440-97-1 ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 5092 - 5095

17
[ 21440-97-1 ]
[ 709027-83-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 2185 - 2189

18
[ 21440-97-1 ]
[ 305800-38-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 2185 - 2189

19
[ 21440-97-1 ]
[ 709028-02-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 2185 - 2189

20
[ 21440-97-1 ]
5-(4,4-dimethyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yl)-1H-pyrrole-2-carbaldehyde [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 2185 - 2189

21
[ 21440-97-1 ]
[ 709027-91-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 2185 - 2189

22
[ 21440-97-1 ]
4-(4,4-dimethyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yl)-1H-pyrrole-3-carbonitrile [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 2185 - 2189

23
[ 21440-97-1 ]
2-(4,4-dimethyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yl)-1-methyl-1H-pyrrole-3-carbonitrile [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 2185 - 2189

24
[ 21440-97-1 ]
4-(4,4-dimethyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yl)-1-methyl-1H-pyrrole-3-carbonitrile [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 2185 - 2189

25
[ 21440-97-1 ]
5-(4,4-dimethyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yl)-oxazole-2-carbaldehyde oxime [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 2185 - 2189

26
[ 21440-97-1 ]
5-(4,4-dimethyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yl)-oxazole-2-carbonitrile [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 2185 - 2189

27
[ 21440-97-1 ]
4,4-dimethyl-6-(5-nitro-1H-pyrrol-2-yl)-1,4-dihydro-benzo[d][1,3]oxazin-2-one [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 2185 - 2189

28
[ 21440-97-1 ]
[ 709027-93-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 2185 - 2189

29
[ 21440-97-1 ]
[ 709027-90-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 2185 - 2189

30
[ 21440-97-1 ]
5-bromo-4-(4,4-dimethyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yl)-1-methyl-1H-pyrrole-3-carbonitrile [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 2185 - 2189

31
[ 21440-97-1 ]
5-bromo-4-(4,4-dimethyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yl)-1H-pyrrole-3-carbonitrile [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 2185 - 2189

32
[ 21440-97-1 ]
4,4-dimethyl-6-(5-trifluoroacetyl-1H-pyrrol-2-yl)-1,4-dihydro-benzo[d][1,3]oxazin-2-one [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 2185 - 2189

33
[ 21440-97-1 ]
[ 709027-80-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 2185 - 2189

34
[ 21440-97-1 ]
6-(2-bromo-1H-pyrrol-3-yl)-1-diethoxymethyl-4,4-dimethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 2185 - 2189

35
[ 21440-97-1 ]
[ 709028-04-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 2185 - 2189

36
[ 21440-97-1 ]
[ 305800-36-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 2185 - 2189

37
[ 21440-97-1 ]
5-bromo-4-(1-diethoxymethyl-4,4-dimethyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yl)-1-methyl-1H-pyrrole-3-carbonitrile [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 2185 - 2189

38
[ 21440-97-1 ]
[ 709028-05-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 2185 - 2189

39
[ 21440-97-1 ]
5-bromo-4-(1-diethoxymethyl-4,4-dimethyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yl)-1H-pyrrole-3-carbonitrile [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 2185 - 2189

40
[ 21440-97-1 ]
[ 709028-07-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 2185 - 2189

41
[ 21440-97-1 ]
[ 304854-47-5 ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 4379 - 4382

42
[ 21440-97-1 ]
[ 304853-31-4 ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 4379 - 4382

43
[ 21440-97-1 ]
[ 304853-36-9 ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 4379 - 4382

44
[ 21440-97-1 ]
[ 304854-09-9 ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 4379 - 4382

45
[ 21440-97-1 ]
[ 304854-45-3 ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 4379 - 4382

46
[ 21440-97-1 ]
[ 304853-30-3 ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 4379 - 4382

47
[ 21440-97-1 ]
[ 304854-07-7 ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 4379 - 4382

48
C₁₅H₂₆BN₂O₃^(1-)*Li⁽¹⁺⁾ [ No CAS ]
C₁₈H₂₄BN₄O₂^(1-)*Li⁽¹⁺⁾ [ No CAS ]
[ 21440-97-1 ]
[ 304854-00-0 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; at 70℃;Product distribution / selectivity;	In yet another embodiment, 5-(4,4-dimethyl-2-oxo-1,4-dihydro-2H-3,1- benzoxazin-6-yl)- l H-pyrrole-2-carbonitrile is prepared by reacting 1-methyl-pyrrole- 2-carbonitrile, a slight excess (about 1.3 equivalents) of lithium di-isopropylamide (LDA) and tri-isopropylborate in tetrahydrofuran (THF) at a reduced temperature of about-2 to about 8 C to give a boronate/borinate mixture. This mixture is then treated in situ with a limiting amount (about 1 equivalent) of the BrofoxineNo. reagent, potassium carbonate, and tetrakis(triphenylphosphine) palladium in THF at elevated temperatures, desirably not exceeding about 70C to give 5-(4,4-dimethyl-2-oxo-1,4- dihydro-2H-3,1-benzoxazin-6-yl)-1H-pyrrole-2-carbonitrile in an unpurified form.

Reference： [1]Patent: WO2005/105817,2005,A2 .Location in patent: Page/Page column 20

49
[ 21440-97-1 ]
[ 67492-50-6 ]
[ 304854-14-6 ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 61 6-(3,5-dichloro-phenyl)4,4-dimethyl-1,4-dihydrobenzo-[d][1,3]oxazin-2-one Prepared from 6-bromo-4,4-dimethyl-1,4-dihydro-benzo[d] [1,3]oxazin-2-one and 3,5-dichlorophenyl boronic acid according to Procedure A. A white solid: mp 245-246 C.; 1H-NMR (DMSO-d6) delta10.4 (s, 1H), 7.77 (m, 2H), 7.67-7.64 (m, 2H), 7.56 (bs, 1H), 6.96 (d, 1H, J=7.98 Hz), 1.7 (s, 6H); MS (EI) m/z 321 ([M+H]+, 40%); Anal. Calc. For C16H13Cl2NO2: C, 59.32, H, 4.11, N, 4.32. Found: C, 59.13, H, 4.29 N, 4.17.
		EXAMPLE 61 6-(3,5dichloro-phenyl)-4,4-dimethyl-1,4-dihydrobenzo-[d][1,3]oxazin-2-one Prepared from <strong>[21440-97-1]6-bromo-4,4-dimethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one</strong> and 3,5-dichlorophenyl boronic acid according to Procedure A. A white solid: mp 245-246 C.; 1H-NMR (DMSO-d6) delta10.4 (s, 1H), 7.77 (m, 2H), 7.67-7.64 (m, 2H), 7.56 (bs, 1H), 6.96 (d, 1H, J=7.98 Hz), 1.7 (s, 6H); MS (EI) m/z 321 ([M+H]+, 40%); Anal. Calc. For C16H13Cl2NO2: C, 59.32, H, 4.11, N, 4.32. Found: C, 59.13, H, 4.29, N, 4.17.

Reference： [1]Patent: US2002/49204,2002,A1
[2]Patent: US6444668,2002,B1

50
[ 927673-87-8 ]
[ 21440-97-1 ]
6-(3,5-Bis-trifluoromethyl-phenyl)-4,4-dimethyl-1,4-dihydrobenzo [d] [1,3]oxazin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 62 6-(3,5-Bis-trifluoromethyl-phenyl)-4,4-dimethyl-1,4-dihydrobenzo [d] [1,3]oxazin-2-one Prepared from 6-bromo-4,4-dimethyl-1,4-dihydro-benzo[d] [1,3]oxazin-2-one and bis-trifluoromethylphenyl boronic acid according to Procedure A. A white solid: mp 258-260 C.; 1H-NMR (DMSO-d6) delta10.4 (s, 1H), 8.35 (s, 2H), 8.05 (s, 1H), 7.79-7.76 (m, 2H), 7.01 (d, 1H, J=8.01 Hz), 1.7 (s, 6H); MS (ESI) m/z 390 ([M+H]+, 20%); Anal. Calc. For C18H13F6NO2: C, 55.54, H, 3.37, N, 3.6. Found: C, 55.5, H, 3.54, N, 3.47.
		EXAMPLE 62 6-(3,5-Bis-trifluoromethyl-phenyl)-4,4-dimethyl-1,4-dihydrobenzo[d][1,3]oxazin-2-one Prepared from <strong>[21440-97-1]6-bromo-4,4-dimethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one</strong> and bis-trifluoromethylphenyl boronic acid according to Procedure A. A white solid: mp 258-260 C.; 1H-NMR (DMSO-d6) delta10.4 (s, 1H), 8.35 (s, 2H), 8.05 (s, 1H), 7.79-7.76 (m, 2H), 7.01 (d, 1H, J=8.01 Hz), 1.7 (s, 6H); MS (ESI) m/z 390 ([M+H]+, 20%); Anal. Calc. For C18H13F6NO2: C, 55.54, H, 3.37, N, 3.6. Found: C, 55.5, H, 3.54, N, 3.47.

Reference： [1]Patent: US2002/49204,2002,A1
[2]Patent: US6444668,2002,B1

51
[ 60811-21-4 ]
[ 21440-97-1 ]
[ 304854-45-3 ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 65 6-(3-Chloro-4-fluoro-phenyl)-4,4-dimethyl-1,4-dihydro-benzo [d] [1,3]oxazin-2-one Prepared from 6-bromo-4,4-dimethyl-1,4-dihydro-benzo[d] [1,3]oxazin-2-one and <strong>[60811-21-4]1-bromo-3-chloro-4-fluorobenzene</strong> according to Procedure A. White solid: mp 211-212 C.; 1H-NMR (DMSO-d6) delta10.4 (s, 1H), 7.92 (dd, 1H, J=7.13, 2.19 Hz), 7.71-7.66 (m, 1H), 7.60-7.57 (m, 2H), 7.49 (t, 1H, J=8.95 Hz), 6.96 (d, 1H, J=8.01 Hz), 1.67 (s, 6H); MS (EI) m/z 305 ([M+H]+, 20%); Anal. Calc. For C16H13ClFNO2: C, 62.86, H, 4.29, N, 4.58. Found: C, 62.52, H, 4.45, N, 4.42.
		EXAMPLE 65 6-(3-Chloro-4-fluoro-phenyl)-4,4-dimethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one Prepared from 6-bromo-4,4-dimethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one and <strong>[60811-21-4]1-bromo-3-chloro-4-fluorobenzene</strong> according to Procedure A. White solid: mp 211-212 C.; 1H-NMR (DMSO-d6) delta10.4 (s, 1H), 7.92 (dd, 1H, J=7.13, 2.19 Hz), 7.71-7.66 (m, 1H), 7.60-7.57 (m, 2H), 7.49 (t, 1H, J=8.95 Hz), 6.96 (d, 1J=8.01 Hz), 1.67 (s, 6H); MS (EI) m/z 305 ([M +H]+, 20%); Anal. Calc. For C16H13ClFNO2: C, 62.86, H, 4.29, N, 4.58. Found: C, 62.52, H, 4.45, N, 4.42.

Reference： [1]Patent: US2002/49204,2002,A1
[2]Patent: US6444668,2002,B1

52
[ 10365-98-7 ]
[ 21440-97-1 ]
[ 304854-36-2 ]
6-(3-Methoxyphenyl)-4,4-dimethyl-1,4-dihydro-2H-3,1-benzoxazine-2-thione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 52 6-(3-Methoxyphenyl)-4,4-dimethyl-1,4-dihydro-2H-3,1-benzoxazine-2-thione 6-(3-Methoxy-phenyl)-4,4-dimethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one was prepared, according to the procedure of Example 4 from <strong>[21440-97-1]6-bromo-4,4-dimethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one</strong> and 3-methoxyphenyl boronic acid, as a yellow solid: mp 164-165 C.; 1H-NMR (DMSO-d6) delta10.3 (s, 1H), 7.56 (m, 2H), 7.36 (t, 1H, J=7.89Hz), 7.20 (m, 2H), 6.96 (d, 1H, J=8.88 Hz), 6.91 (dd, 1H, J=8.13, 2.35 Hz), 3.8 (s, 3H), 1.7 (s, 6H), MS (ESI) m/z 284 ([M+H]+, 30%); Anal. Calc. For C17H17NO3; C, 72.07; H, 6.05; N, 4.94. Found: C, 70.58; H, 5.73; N, 4.67. The title compound was prepared, according to the procedure of Example 16 starting with 6-(3-Methoxy-phenyl)-4,4-dimethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one, as a white solid: mp 142-143 C.; 1H-NMR (CDCl3) delta8.96 (s, 1H), 7.51 (dd, 1H, J=8.2, 1.84 Hz), 7.40-7.35 (m, 2H), 7.13-7.10 (m, 1H), 7.05 (t, 1H, J=2.21 Hz), 6.90 (dd, 1H, J=8.09, 2.46 Hz), 6.87 (d, 1H, J=8.2 Hz), 3.87 (s, 3H), 1.8 (s, 6H), MS (ES) m/z 298 ([M-H]-).

Reference： [1]Patent: US6436929,2002,B1

53
[ 19172-47-5 ]
[ 21440-97-1 ]
[ 304853-34-7 ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 10 6-Bromo-4,4-dimethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-thione The product was prepared, from <strong>[21440-97-1]6-bromo-4,4-dimethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one</strong> and Lawesson's reagent using the procedure of Example 9, as a white solid: mp 221-222.5 C.; 1H-NMR (CDCl3) delta9.38 (s, 1H, D2O exchangeable), 7.42 (dd, 1H, J=8.5, 2.1 Hz), 7.29 (d, 1H, J=2.0 Hz), 6.76 (d, 1H, J=8.4 Hz), 1.76 (s, 6H); MS (EI) m/z 272 ([M+H]+, 94%), 274 ([M+H]+, 100%).

Reference： [1]Patent: US6436929,2002,B1

54
[ 79-06-1 ]
[ 21440-97-1 ]
[ 1176219-46-7 ]

Yield	Reaction Conditions	Operation in experiment
57%	With N-Methyldicyclohexylamine;tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; In 1,4-dioxane; hexane; at 20℃;	Example 4 (2E)-3-(4,4-Dimethyl-2-oxo-1,4-dihydro-2H-3,1-benzoxazin-6-yl)acrylamide; A mixture <strong>[21440-97-1]6-bromo-4,4-dimethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one</strong> (1.0 g, 3.90 mmol), prepared in step 2 of Example 2, acrylamide (305 mg, 4.295 mmol), N,N-dicyclohexylmethylamine (0.91 mL, 4.295 mmol) and tri-tert-butylphosphine (52.6 mg of 90% technical grade; 0.234 mmol) in dioxane (5 mL) was purged with nitrogen. Tris(dibenzylideneacetone)dipalladium (0) (107 mg, 0.117 mmol) was added and the mixture again purged with nitrogen and then stirred under nitrogen at room temperature. After approximately 1.5 hours, the reaction had become a solid mass. Ethyl acetate was added, the solids were broken up and then stirred for 5 minutes. This mixture was filtered through silica gel. The silica gel was rinsed with ethyl acetate and the combined filtrates concentrated under reduced pressure to give an orange oil (500 mg). Analysis of the oil indicated that it was mostly dibenzylideneacetone. The silica gel was also rinsed with methanol. The methanol solution was concentrated under reduced pressure to give an off-white solid. Recrystallization of the solid from isopropyl alcohol gave the title compound (0.55 g, 57%) as an off-white solid, mp 196-198 C., MS (ESI) m/z 247, MS (ESI) m/z 245; Anal. Caled. for C13H14N2O3. 0.29 C3H8O: C, 63.18; H, 6.24; N, 10.62. Found: C, 63.03; H, 6.45; N, 10.28.

Reference： [1]Patent: US2009/197878,2009,A1 .Location in patent: Page/Page column 12

55
[ 292638-85-8 ]
[ 21440-97-1 ]
[ 1176219-42-3 ]

Yield	Reaction Conditions	Operation in experiment
82%	With N-Methyldicyclohexylamine;tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; In 1,4-dioxane; hexane; at 20℃;	Step 3: Methyl(2E)-3-(4,4-dimethyl-2-oxo-1,4-dihydro-2H-3,1-benzoxazin-6-yl)acrylate; A mixture of <strong>[21440-97-1]6-bromo-4,4-dimethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one</strong> (2.56 g, 10 mmol), prepared in the previous step, and tris(dibenzylideneacetone)dipalladium (0) (275 mg, 0.3 mmol) was purged with nitrogen. To this mixture was added methyl acrylate, (990 muL, 11 mmol), tri-tert-butylphosphine (1.86 mL, 10% by weight in hexane; 0.6 mmol), N,N-dicyclohexylmethylamine (2.33 mL, 11 mmol) and 10 mL of dioxane, in that order. The reaction was again purged with nitrogen and then stirred at room temperature. After a few hours, an LC/MS indicated that the starting material was gone. The reaction was dissolved in ethyl acetate and filtered through silica gel. The filtrate was concentrated under reduced pressure to give a yellow solid (3.1 g). Purification of the solid on a Horizon Flash Collector (Biotage Si column) using a linear gradient of 5% ethyl acetate-hexane to 50% ethyl acetate-hexane gave a light yellow solid (2.14 g). By thin layer chromatography (TLC) analysis the material was not pure. The solid was again purified on a Horizon Flash silicon column (Biotage), this time using a linear gradient of 5% ethyl acetate-methylene chloride to 20% ethyl acetate-methylene chloride as the eluent. After removal of the solvent under reduced pressure, the title compound (2.14 g, 82%) was isolated as a white solid, mp 204-205 C., MS (ESI) m/z 262, MS (ESI) m/z 260; Anal. Calcd. for C14H15NO4: C, 64.36; H, 5.79; N, 5.36. Found: C, 64.25; H, 5.99; N, 5.25.

Reference： [1]Patent: US2009/197878,2009,A1 .Location in patent: Page/Page column 11

56
[ 625-37-6 ]
[ 21440-97-1 ]
[ 1176219-72-9 ]

Yield	Reaction Conditions	Operation in experiment
8%	With N-Methyldicyclohexylamine;tris-(dibenzylideneacetone)dipalladium(0); tri-tert-butyl phosphine; In 1,4-dioxane; at 20℃;	Example 16 General Procedure for Examples 16 to 30; A mixture of the appropriate aryl bromide (2.0 mmol), alkylene (2.2 mmol), N,N-dicyclohexylmethylamine (470 muL, 2.2 mmol) and tri-tert-butylphosphine (24 mg, 0.12 mmol) in dioxane (5 mL) was purged with nitrogen. Tris(dibenzylideneacetone)dipalladium (0) (55 mg, 0.06 mmol) was added and the mixture again purged with nitrogen and then stirred at room temperature. The reaction was monitored by LC/MS. If necessary, more catalyst was added. The reaction was diluted with ethyl acetate and filtered through a small amount of silica gel. The silica gel was rinsed with ethyl acetate and then methanol. The filtrates were kept separate and each concentrated under reduced pressure. The residues from the filtrates were analyzed for product by use of LC/MS. The product was purified by the methods described.; Step 3: (2E)-3-(2-Oxo-1,2-dihydrospiro[3,1-benzoxazine-4,1'-cyclohexan]-6-yl)but-2-enamide6-Bromospiro[4H-3,1-benzoxazine-4,1'-cyclohexan]-2(1H)-one (592 mg, 2.0 mmol), prepared in the previous step, and (E)-but-2-enamide (187 mg, 2.2 mmol) were reacted according to the General Procedure described above. By LC/MS, the methanol filtrate contained the product. The methanol filtrate was concentrated under reduced pressure to remove the solvent. The residue was taken up in ethyl acetate. Upon standing some solid precipitated. The solid was collected by filtration and dried under reduced pressure. By nuclear magnetic resonance (NMR) analysis, the solid contained ethyl acetate. The solid was taken up in methanol-methylene chloride and concentrated under reduced pressure. It was then taken up in methylene chloride and again concentrated under reduced pressure. This process was repeated two additional times and then the solid was dried under reduced pressure to give the title compound (50 mg, 8%) as a white solid, mp 204-207 C. (dec), MS m/z 301, MS m/z 299.

Reference： [1]Patent: US2009/197878,2009,A1 .Location in patent: Page/Page column 14

57
[ 683-57-8 ]
[ 21440-97-1 ]
[ 1245220-53-4 ]

Yield	Reaction Conditions	Operation in experiment
73%		2-(6-bromo-4,4-dimethyl-2-oxo-3,1-benzoxazin-1-yl)acetamide (Compound 2) A mixture of potassium carbonate (0.675 g, 4.881 mmol), commercial 6- bromo-4,4-dimethyl-1 ,4-dihydro-benzo[d][1 ,3]oxazin-2-one (0.500 g, 1 .952 mmol) and 2-bromoacetamide (0.404 g, 2.929 mmol) in Lambda/,Lambda/-dimethylformamide (8 ml) was stirred and heated (700C) for 3 hours. The resulting reaction mixture was quenched with ice-cold water, and the solid precipitated was filtered, washed with hexane and dried under vacuum, to afford the title compound (0.450 g) as an off white solid (73% yield).M.p. 234.8-236.00C.LC-ESI-HRMS of [M+Na]+ shows 363.03068 Da. CaIc. 363.031506 Da, dev. -2.3 ppm
73%	With potassium carbonate; In N,N-dimethyl-formamide; at 70℃; for 3h;	A mixture of potassium carbonate (0.675 g, 4.881 mmol), commercial <strong>[21440-97-1]6-bromo-4,4-dimethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one</strong> (0.500 g, 1.952 mmol) and 2-bromoacetamide (0.404 g, 2.929 mmol) in N,N-dimethylformamide (8 ml) was stirred and heated (70 C.) for 3 hours. The resulting reaction mixture was quenched with ice-cold water, and the solid precipitated was filtered, washed with hexane and dried under vacuum, to afford the title compound (0.450 g) as an off white solid (73% yield).M.p. 234.8-236.0 C.LC-ESI-HRMS of [M+Na]+ shows 363.03068 Da. Calc. 363.031506 Da, dev. -2.3 ppm

Reference： [1]Patent: WO2010/103064,2010,A1 .Location in patent: Page/Page column 16
[2]Patent: US2012/71471,2012,A1 .Location in patent: Page/Page column 6; 7

58
C₁₅H₂₆BN₂O₃^(1-)*Li⁽¹⁺⁾ [ No CAS ]
[ 21440-97-1 ]
[ 304854-00-0 ]

Yield	Reaction Conditions	Operation in experiment
		j00092j Step 2: The <strong>[21440-97-1]brofoxine</strong> reagent (1 eq.), THF (3.5-4 vol. vs. <strong>[21440-97-1]brofoxine</strong>) and a potassium carbonate (1.95 eq. vs. <strong>[21440-97-1]brofoxine</strong>)/water solution (3.5 vol. vs. <strong>[21440-97-1]brofoxine</strong>) were combined under an atmosphere of nitrogen. Pd(OAc)2 (0.008 eq. vs. <strong>[21440-97-1]brofoxine</strong>) or triphenylphosphine (0.035 eq. vs. <strong>[21440-97-1]brofoxine</strong>) in THF (0.77 vol. vs. <strong>[21440-97-1]brofoxine</strong>) was added to the <strong>[21440-97-1]brofoxine</strong> mixture and heated to about 85C.j00093j The boronate intermediate was then added to the <strong>[21440-97-1]brofoxine</strong> mixture over a period of not less than 6 - 7 hours at reflux. The reaction was monitored by HPLC and addition of the boronate intermediate was ceased when HPLC indicated that the reaction was complete.j00094j The mixture was then rinsed using THF (0.77 vol. vs. <strong>[21440-97-1]brofoxine</strong>) and cooled to 19 to 25C. THF (0.77 vol. vs. <strong>[21440-97-1]brofoxine</strong>) and water (6.5 vol. vs. <strong>[21440-97-1]brofoxine</strong>) were added, the mixture stirred until all of the solid material dissolved or was suspended, and the mixture cooled to 5 to 11C. The pH of the mixture was adjusted to a pH of 4 to 5 using hydrochloric acid or sodium hydroxide, while maintaining a temperature of 5 to 15 C. The mixture was rinsed using water, then heated to 19 to 25C for at least 30 minutes with stirring, and then settled for at least 30 minutes.1000951 L-Cysteine (0.35 eq. vs. <strong>[21440-97-1]brofoxine</strong>) and THF were added to the organic layer, THF added, and the mixture cooled to about 20C for not less than 2 hours. The L-cysteine was removed by filtration and the filtrate rinsed with THF.j00096j Toluene/heptane was then added, the mixture concentrated under reduced pressures at a temperature of less than 45C. A second aliquot of toluene/heptanes was added, the mixture concentrated under reduced temperature of less than 45C. The temperature was adjusted to 19 to 25 C. Heptane was added and the mixture stirred for at least 60 minutes. The mixture was filtered and the filter cake slurried with acetone/water until the boronate intermediate was removed. The wet cake was dried at less than 45C.

Reference： [1]Patent: WO2014/159377,2014,A1 .Location in patent: Paragraph 00027; 00092; 00093; 00094; 00095; 00096

59
[ 100-53-8 ]
[ 21440-97-1 ]
C₁₇H₁₇NO₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	With tris-(dibenzylideneacetone)dipalladium(0); N-ethyl-N,N-diisopropylamine; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 100℃; for 5h;Inert atmosphere;	A solution of 61(500 mg, 1.95 mmol), benzyl mercaptan (0.34 mL, 2.92 mmol), i-Pr2NEt (1.03 mL, 5.90mmol), Pd2(dba)3 (90 mg, 0.098 mmol) and XantPhos (113mg, 0.195 mmol) in dioxane (10 mL) was degassed with N2 for 5 min.The mixture was then heated to 100 C for 5 h. The crude reaction mixture was dry-loaded onto silica gel and purified via ISCO flash column chromatography(eluting with 40% EtOAc in hexanes) to afford 62 (550 mg, 94%).

Reference： [1]Bioorganic and Medicinal Chemistry,2016,vol. 24,p. 1384 - 1391

60
[ 21440-97-1 ]
C₂₃H₂₀BrFN₂O₅S [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2016,vol. 24,p. 1384 - 1391

61
[ 21440-97-1 ]
C₂₃H₁₉FN₂O₅S [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2016,vol. 24,p. 1384 - 1391

62
[ 21440-97-1 ]
C₂₃H₁₉FN₂O₄S₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2016,vol. 24,p. 1384 - 1391

63
[ 21440-97-1 ]
C₁₀H₁₀ClNO₄S [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2016,vol. 24,p. 1384 - 1391

64
[ 21440-97-1 ]
C₁₆H₁₄⁽¹⁸⁾FN₃O₂ [ No CAS ]

Reference： [1]RSC Advances,2016,vol. 6,p. 57569 - 57579

65
[ 21440-97-1 ]
[ 304853-99-4 ]

Reference： [1]RSC Advances,2016,vol. 6,p. 57569 - 57579

66
[ 21440-97-1 ]
C₁₆H₁₄FN₃O₂ [ No CAS ]

Reference： [1]RSC Advances,2016,vol. 6,p. 57569 - 57579

67
[ 21440-97-1 ]
[ 73183-34-3 ]
[ 1246765-40-1 ]

Yield	Reaction Conditions	Operation in experiment
98%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 90℃; for 4h;Inert atmosphere;	To a solution of 6-bromo-4,4-dimethyl-1 ,4-dihydro-2H-3, 1-benzoxazin-2-one (500 mg, 1.95 mmol) in 1 ,4-dioxane (10 mL) under a N2 atmosphere, potassium acetate (575 mg, 5.86 mmol) and bis(pinacolato)diboron (744 mg, 2.93 mmol) were added. The reaction mixture was then sparge degassed with N2. [1 , 1 '-bis(diphenylphosphino)ferrocene]palladium (II) chloride dichloromethane complex (80 mg, 0.10 mmol) was added and the reaction mixture was then heated at 90C for 4 h. On cooling the reaction mixture was partitioned between DCM (50 mL) and H2O (50 mL). The layers were separated and the aq. layer was extracted with DCM (2 x 40 ml_). The organic layers were combined, dried over MgSCU, filtered and concentrated under reduced pressure to afford the crude reaction product. Purification was by column chromatography using a gradient of 0-50 % EtOAc in DCM as the eluent. All product containing fractions were combined and concentrated to yield 4,4-dimethyl-6- (4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-1/-/-3, 1-benzoxazin-2-one (579 mg, 98 % yield). LCMS (Method F) 304.1 [M+H]+; RT 1.93 min.

Reference： [1]Patent: WO2017/46605,2017,A1 .Location in patent: Page/Page column 70-71

68
5-cyclopropyl-6-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-oxazolo[4,5-c]quinolin-4-one [ No CAS ]
[ 21440-97-1 ]
6-{5-cyclopropyl-6-methyl-4-oxo-oxazolo[4,5-c]quinolin-7-yl}-4,4-dimethyl-2,4-dihydro-1H-3,1-benzoxazin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With chloro(2-dicyclohexylphosphino-2?,4?,6?-triisopropyl-1,1?-biphenyl)[2-(2?-amino-1,1?-biphenyl?)]palladium(II); XPhos;	Prepared using method described in Example 4, step (a) with 5-cyclopropyl-6-methyl-7- (tetramethyl-1 ,3,2-dioxaborolan-2yl)-oxazolo[4,5-c]quinolin-4-one (Intermediate D) and 6- bromo-4,4-dimethyl-2,4-dihydro-1 H-3, 1-benzoxazin-2-one. Chloro(2-dicyclohexylphosphino- 2',4',6'-triisopropyl-1 ,r-biphenyl)[2-(2'-amino-1,r-biphenyl)]palladium(l l) (10% mmol) was used as catalyst and 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (10% mmol) as ligand. Column chromatography was carried out, eluting with 0-100% EtOAc in DCM. 1 H N MR (Method A) (CDC ): delta ppm 8.87 (s, 1 H), 8.10 (s, 1 H), 7.78 (d, J = 8.0 Hz, 1 H), 7.31 (dd, J = 8.2, 1 .9 Hz, 1 H), 7.24 (d, 1 H), 7.16 (d, J =1.9 Hz, 1 H), 7.01 (d, J = 8.1 Hz, 1 H), 3.66 (dd, J = 6.9, 3.1 Hz, 1 H), 2.54 (s, 3H), 1 .79 (s, 6H), 1.33 - 1.28 (m, 2H), 0.75 - 0.66 (m, 2H); LC-MS (Method D) 416.2 [M+H]+; RT 2.22 min

Reference： [1]Patent: WO2017/46605,2017,A1 .Location in patent: Page/Page column 90-91

69
[ 551-93-9 ]
[ 21440-97-1 ]

Reference： [1]Patent: WO2018/17490,2018,A1

70
[ 75-03-6 ]
[ 21440-97-1 ]
6-bromo-4,4-dimethyl-1-ethyl-3.1-benzoxazin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99%		6-bromo-4,4-dimethyl-lH-3,l-benzoxazin-2-one (250 mg, 0.976 mmol) was dissolved in dimethylformamide (5 mL) and potassium carbonate (0.204 g, 1.46 mmol) was added. The suspension was stirred for 10 min and then iodoethane (0.158 mL, 1.95 mmol) was added. The reaction mixture was heated to 60C and stirred for 4 h. The reaction mixture was poured into ice/water and then extracted with ethyl acetate (3x20 mL). The combined organic layers were washed with brine (2x20 mL). dried and concentrated. The crude oil was purified by flash chromatography to give the desired compound (0.275 g, 99%) as a colorless oil. LCMS: 0.98 min; ES+ 284/286 (M+H+); XH NMR (CHLOROFORM-d, 400MHz): delta (ppm) 7.43 (d,lH), 7.28 (s, 1H), 6.86 (d, 1H), 3.98 (q, 2H), 1.67 (s, 6H), 1.32 (t, 3H)

Reference： [1]Patent: WO2018/17490,2018,A1 .Location in patent: Paragraph 0169; 0170

71
[ 15833-00-8 ]
[ 21440-97-1 ]

Reference： [1]Patent: WO2018/17490,2018,A1

72
[ 21440-96-0 ]
[ 21440-97-1 ]

Yield	Reaction Conditions	Operation in experiment
	With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 0 - 20℃; for 4h;	4,4-dimethyl-lH-3,l-benzoxazin-2-one (1.00 g, 5.64 mmol) was dissolved in dimethylformamide (11 mL) and cooled to 0C. NBS (1.12 g, 6.21 mmol) was added. The reaction mixture was stirred at room temperature for 4 h.The reaction mixture was poured on water and the white precipitate was filtered and washed with water to give 6-bromo-4,4- dimethyl-lH-3,l-benzoxazin-2-one as a white powder (1.29 g, 89% LCMS: 0.83 min; ES+ 256/258 (M+H+); XH NMR (CHLOROFORM-d, 400MHz): delta (ppm) 9.13 (br s, 1H), 7.36 (d, 1H), 7.27 (s, 1H), 6.77 (d, 1H), 1.73 (s, 6H).yield).

Reference： [1]Patent: WO2018/17490,2018,A1 .Location in patent: Paragraph 0167; 0168

73
[ 21440-97-1 ]
N-(1-ethyl-4,4-dimethyl-2-oxo-3.1-benzoxazin-6-yl)-1-(p-tolyl)methanesulfonamide [ No CAS ]

Reference： [1]Patent: WO2018/17490,2018,A1

74
[ 135484-83-2 ]
[ 75-16-1 ]
[ 21440-97-1 ]

Yield	Reaction Conditions	Operation in experiment
72.8%		Add 50g compound 16 to the 1L three-neck bottleThen add 500ml THF,Replace the air in the reaction flask with nitrogen,The reaction system is cooled to 0 C,Slowly add 160 ml of MeMgBr (3M in THF) under nitrogen protection.After maintaining the temperature for 1 h, the reaction was stirred for 6 h after warming to room temperature.38.8 g of N,N'-carbonyldiimidazole (CDI) was added to monitor the complete reaction of the starting materials.Continue to stir for 3h,The reaction was then quenched by the addition of saturated NH 4Cl solution.The solution was separated and the aqueous phase was extracted twice with dichloromethane, 100 ml each time.The organic phase is combined and washed once with saturated brine.Dry anhydrous Na2SO4 for 1 h, remove the desiccant by filtration,After the filtrate was concentrated, the target product compound 17 was obtained as a white solid 40.5 g.The yield was 72.8%.

Reference： [1]Patent: CN108912138,2018,A .Location in patent: Paragraph 0153-0155

75
[ 21440-97-1 ]
C₂₈H₂₀BrN₃O₄ [ No CAS ]

Reference： [1]Patent: CN108912138,2018,A

76
[ 21440-97-1 ]
C₂₇H₂₀BrN₃O₂ [ No CAS ]

Reference： [1]Patent: CN108912138,2018,A

77
[ 21440-97-1 ]
C₂₇H₂₂BrN₃ [ No CAS ]

Reference： [1]Patent: CN108912138,2018,A

78
[ 21440-97-1 ]
C₂₇H₂₁BrN₂ [ No CAS ]

Reference： [1]Patent: CN108912138,2018,A

79
[ 21440-97-1 ]
C₃₉H₃₀ClN₃ [ No CAS ]

Reference： [1]Patent: CN108912138,2018,A

80
[ 21440-97-1 ]
C₃₉H₂₉N₃ [ No CAS ]

Reference： [1]Patent: CN108912138,2018,A

81
[ 21440-97-1 ]
C₅₇H₄₀N₄ [ No CAS ]

Reference： [1]Patent: CN108912138,2018,A

82
[ 86-74-8 ]
[ 21440-97-1 ]
C₂₂H₁₈N₂O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80.6%	With 1,10-Phenanthroline; potassium carbonate; copper(I) bromide; In N,N-dimethyl-formamide; at 120℃; for 10h;Inert atmosphere;	With a thermometer,Add 40g compound 17, to the 1L three-neck bottle of the condenser28.7 g carbazole, 32.3 g K2CO3, 0.62 g 1,10-Phenanthroline,Then 450 ml of DMF was added.Replace the air in the reaction system with nitrogen,Add 0.45 g of CuBr under nitrogen protection.Heat to 120 C for 10 h,After the TLC was monitored, the starting material was completely reacted and the stirring was stopped and lowered to room temperature.The reaction system is added to 3 volumes of water,The product was precipitated by stirring and filtered.The filter cake was completely dissolved in 500 ml of dichloromethane (DCM) and washed 3 times with water.150ml each time. The organic phase is dried and concentrated.The crude product was passed through a silica gel column to give compound 18 as a white solid, 43.1 g, yield 80.6%.

Reference： [1]Patent: CN108912138,2018,A .Location in patent: Paragraph 0153; 0157; 0158

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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. 21440-97-1 ] {[proInfo.proName]}

Quality Control of [ 21440-97-1 ]

Related Doc. of [ 21440-97-1 ]

Product Details of [ 21440-97-1 ]

Safety of [ 21440-97-1 ]

Application In Synthesis of [ 21440-97-1 ]

[ 21440-97-1 ] Synthesis Path-Upstream 1~6

[ 21440-97-1 ] Synthesis Path-Downstream 1~82

Related Functional Groups of [ 21440-97-1 ]

Bromides

Amides

Related Parent Nucleus of [ 21440-97-1 ]

Other Aromatic Heterocycles

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 21440-97-1 ]

Related Parent Nucleus of
[ 21440-97-1 ]