19932-85-5|6-Bromobenzo[d]oxazol-2(3H)-one| Ambeed

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Quality Control of [ 19932-85-5 ] Purity: 98% SDS Specification

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Product Details of [ 19932-85-5 ]

CAS No. :	19932-85-5
Formula :	C₇H₄BrNO₂
M.W :	214.02
SMILES Code :	BrC1=CC2=C(NC(=O)O2)C=C1
MDL No. :	MFCD00694727
Boiling Point :	No data available
InChI Key :	DDNKJFBQMQOIKI-UHFFFAOYSA-N
Pubchem ID :	29859

Safety of [ 19932-85-5 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H319
Precautionary Statements:	P305+P351+P338

Computational Chemistry of [ 19932-85-5 ] Show Less

Physicochemical Properties

Num. heavy atoms	11
Num. arom. heavy atoms	9
Fraction Csp3	0.0
Num. rotatable bonds	0
Num. H-bond acceptors	2.0
Num. H-bond donors	1.0
Molar Refractivity	44.53
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	46.0 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.65
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	1.85
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	1.88
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	1.59
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	2.72
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.94

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.94
Solubility	0.247 mg/ml ; 0.00115 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-2.44
Solubility	0.783 mg/ml ; 0.00366 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-3.68
Solubility	0.0446 mg/ml ; 0.000208 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	Yes
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	Yes
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-6.29 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	0.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	0.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	2.44

Application In Synthesis of [ 19932-85-5 ]

* 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 [ 19932-85-5 ]

[ 19932-85-5 ] Synthesis Path-Downstream 1~35

1
[ 59-49-4 ]
[ 19932-85-5 ]

Yield	Reaction Conditions	Operation in experiment
94%	With bromine; acetic acid; at 20℃; for 4h;	3H-1,3-Benzoxazol-2-one (5.00 g, 37.00 mmol) was dissolved in acetic acid (50 mL) and bromine (1.9 mL, 37.0 mmol) was added dropwise. The reaction mixture was stirred at 20 C for 4 h.The reaction mixture was poured onto ice and the precipitate was collected by filtration, washed with water and air-dried to give a pink powder (7.48 g, 34.8 mmol, 94%). Mp 191.6-192.3 C. 1H NMR (300 MHz, DMSOd6): δ 11.81 (s, 1H), 7.57 (dd, J = 1.9 Hz, J = 0.3 Hz, 1H), 7.30 (dd, J = 8.3 Hz, J = 1.9 Hz, 1H), 7.04 (dd, J = 8.3 Hz, J = 0.3 Hz, 1H). 13C NMR (75 MHz, DMSOd6): δ 154.5, 144.5, 130.3, 126.9, 113.5, 113.2, 111.7. LCMS m/z calc for [M - H]+: 211.9, 213.9, found: 211.8, 213.8.
94%		3H-1,3-Benzoxazol-2-one (5.00 g, 37.00 mmol) was dissolved in acetic acid (50 mL) and bromine (1.9 mL, 37.0 mmol) was added dropwise. The reaction mixture was stirred at20C for 4 h. The reaction mixture was poured onto ice and the precipitate was collected by filtration, washed with water and air-dried to give 1 as a pink powder (7.48 g, 94%). Mp 191.6C. 1H NMR (300 MHz), (5(ppm, DMSO-d6): 11.81 (s, 1H), 7.57 (dd, J= 1.9 Hz, J0.3 Hz, 1H), 7.30 (dd, J= 8.3 Hz, J= 1.9 Hz, 1H), 7.04 (dd, J 8.3 Hz, J 0.3 Hz, 1H).13C NMR (75 MHz), (5(ppm, DMSO-d6): 154.5, 144.5, 130.3, 126.9, 113.5, 113.2, 111.7.LCMS m/zcalc for [M-H]: 211.9, 213.9, found: 211.8, 213.8.
84%	With bromine; In dichloromethane; at 20℃; for 19.5h;	To a mixture of 3H-benzooxazol-2-one (20 g, 0.15 mol) in DCM (500 mL) was added bromine (8.34 mL, 0.16 mol). After stirring at room temperature for 19.5 h, the orange precipitate that had formed was filtered off and washed with DCM until the orange color was washed out. The filtrate was concentrated to approximately 33% of its original volume and filtered and washed as before. The combined solids weighed 28.36 g. 1H NMR indicated the product was clean albeit contained ca. 8-9% starting material meaning the true yield of product was 26.72 g, 84%.

70%	With N-Bromosuccinimide; In acetic acid; at 20℃; for 72h;	Step 1: N-Bromosuccinimide (26.6 g, 0.15 mol) was added to a stirred solution of 2-benzoxazolinone (20.0 g, 0.15 mol) in glacial acetic acid (220 mL), and the mixture was stirred at room temperature for 3 days. The reaction mixture was poured into H2O (1.2 L), and the white solid that formed was collected. Recrystallization from hot EtOH (300 mL) gave bromide 1 (22.1 g, 70%) as an off-white solid: mp 190-195 C.; IR (KBr): 3278, 1779, 1736, 1623 cm?1; 1H NMR (300 MHz, CD3OD): ?7.41 (d, J=2 Hz, 1H), 7.32 (dd, J=5, 2 Hz, 1H), 6.99 (d, J=5 Hz, 1H); CI MS (methane) (m/z): 215 [M+H]+.
31%	With N-Bromosuccinimide; In acetonitrile; at -15 - 20℃;	Preparation of 6-Bromo-3H-benzoxazol-2-one. To a stirred suspension of 3H-benzoxazol-2-one (1.35 g, 10 mmol) in acetonitrile (23 ML) at -15 C. was added portionwise NBS (2.00 g, 11.0 mmol).Following complete addition of NBS the mixture was stirred at -15 to 0 C. for 3 h then allowed to warm to ambient temperature and stirred overnight.The solvent was evaporated in vacuo and the residue was partitioned between CH2Cl2/H2O precipitating the intermediate title compound, 6-bromo-3H-benzoxazol-2-one, (0.67 g, 31%) as a brown solid. 1HNMR(CDCl3) δ 7.0 (1H, d), 7.15 (1H.,d), 7.3 (1H, s), 11.9 (1H, s).
	With bromine; In dichloromethane; at 20℃; for 19.5h;	To a mixture of 3H-benzooxazol-2-one (20 g, 0.15 mol) in DCM (500 mL) was added bromine (8.34 mL, 0.16 mol). After stirring at room temperature for 19.5 h, the orange precipitate that had formed was filtered off and washed with DCM until the orange color was washed out. The filtrate was concentrated to approximately 33% of its original volume and filtered and washed as before. The combined solids weighed 28.36 g and contained ca. 8-9% starting material.
	With N-Bromosuccinimide; In water; acetic acid;	Step 1: To a solution of benzoxazolinone (20 g, 0.148 mol) in 220 mL glacial acetic acid was added N-bromosuccinimide (NBS, 26.36 g, 0.148 mol), and the reaction mixture was stirred at room temperature for 63 hours before pouring into 1500 mL water. The precipitated product was washed thoroughly with water upon collection and recrystallized from EtOH to give 6-bromo-3H-benzoxazol-2-one (9) (25.09 g, 79%): Theory: C, 39.28; H, 1.88; N, 6.54; Br, 37.33. Found: C, 39.36; H, 2.02; N, 6.36; Br, 37.43. MP 192-194 C.

References: [1]European Journal of Medicinal Chemistry,2018,vol. 159,p. 104 - 125.
[2]Patent: WO2020/11848,2020,A1 .Location in patent: Page/Page column 38; 41-42.
[3]Patent: US6372933,2002,B1 .Location in patent: Page column 5 - 6.
[4]Patent: US2008/138413,2008,A1 .Location in patent: Page/Page column 22.
[5]Monatshefte fur Chemie,2011,vol. 142,p. 67 - 80.
[6]Patent: EP1251128,2002,A1 .Location in patent: Page 38.
[7]Patent: US2003/236252,2003,A1 .Location in patent: Page 14.
[8]Monatshefte fur Chemie,1993,vol. 124,p. 367 - 380.
[9]Patent: US2003/225127,2003,A1 .Location in patent: Page 10.
[10]Journal fur praktische Chemie (Leipzig 1954),1888,vol. <2> 37,p. 28 Anm. 1, 31, 38, 46.
[11]Journal of the Chemical Society,1934,p. 1186,1190.
[12]Collection of Czechoslovak Chemical Communications,1979,vol. 44,p. 1790 - 1798.
[13]Patent: WO2006/86705,2006,A1 .Location in patent: Page/Page column 84.
[14]Acta poloniae pharmaceutica,2013,vol. 70,p. 245 - 253.
[15]European Journal of Medicinal Chemistry,2015,vol. 92,p. 575 - 582.
[16]Patent: US2003/18021,2003,A1 .
[17]ChemMedChem,2018,vol. 13,p. 2522 - 2529.

2
[ 52112-66-0 ]
[ 19932-85-5 ]

References: [1]Patent: US2895877,1956,A .

3
[ 19932-85-5 ]
[ 77-78-1 ]
[ 67927-44-0 ]

References: [1]Journal of the Chemical Society,1938,p. 321,326.

4
[ 19932-85-5 ]
[ 38191-34-3 ]

References: [1]Journal of the Chemical Society,1938,p. 321,326.

5
[ 6322-49-2 ]
[ 19932-85-5 ]
[ 13604-03-0 ]

References: [1]Journal fur praktische Chemie (Leipzig 1954),1966,vol. 33,p. 144 - 148.

6
[ 19932-85-5 ]
[ 50277-65-1 ]
[ 59676-68-5 ]

References: [1]Chemistry of Heterocyclic Compounds,1976,vol. 12,p. 366.
Khimiya Geterotsiklicheskikh Soedinenii,1976,vol. 12,p. 429.

7
[ 19932-85-5 ]
[ 4554-16-9 ]
[ 13610-68-9 ]

References: [1]Journal fur praktische Chemie (Leipzig 1954),1966,vol. 33,p. 130 - 138.

8
[ 19932-85-5 ]
[ 107-13-1 ]
[ 13610-57-6 ]

References: [1]Journal fur praktische Chemie (Leipzig 1954),1966,vol. 33,p. 130 - 138.

9
[ 19932-85-5 ]
[ 598-31-2 ]
[ 13603-99-1 ]

References: [1]Journal fur praktische Chemie (Leipzig 1954),1966,vol. 33,p. 144 - 148.

10
[ 19932-85-5 ]
[ 99-81-0 ]
[ 554-68-7 ]
[ 120007-58-1 ]

References: [1]Chemistry of Natural Compounds,1987,vol. 23,p. 340 - 344.
Khimiya Prirodnykh Soedinenii,1987,p. 411 - 415.

11
[ 19932-85-5 ]
[ 532-27-4 ]
[ 120007-47-8 ]

References: [1]Chemistry of Natural Compounds,1987,vol. 23,p. 340 - 344.
Khimiya Prirodnykh Soedinenii,1987,p. 411 - 415.

12
[ 19932-85-5 ]
[ 816-40-0 ]
[ 93232-04-3 ]

References: [1]Chemistry of Heterocyclic Compounds,1987,vol. 23,p. 1024 - 1026.
Khimiya Geterotsiklicheskikh Soedinenii,1987,p. 1277 - 1279.

13
[ 19932-85-5 ]
[ 814-75-5 ]
[ 113922-38-6 ]

References: [1]Chemistry of Heterocyclic Compounds,1987,vol. 23,p. 1024 - 1026.
Khimiya Geterotsiklicheskikh Soedinenii,1987,p. 1277 - 1279.

14
[ 19932-85-5 ]
[ 24316-84-5 ]

References: [1]Synthesis,1983,p. 936 - 937.

15
[ 19932-85-5 ]
[ 7148-74-5 ]
6-bromo-3-(2-bromo-propionyl)-3H-benzooxazol-2-one [ No CAS ]

References: [1]Chemistry of Heterocyclic Compounds,1999,vol. 35,p. 240 - 243.

17
diazotized 6-amino-3H-benzoxazol-2-one [ No CAS ]
[ 19932-85-5 ]

References: [1]Przemysl Chemiczny,1958,vol. 37,p. 418,419.
Chem.Abstr.,1959,p. 5246.

18
[ 19932-85-5 ]
[ 7732-18-5 ]
chloro water [ No CAS ]
6-bromo-3-chloro-3H-benzoxazol-2-one [ No CAS ]

References: [1]Journal fur praktische Chemie (Leipzig 1954),1888,vol. <2> 37,p. 28 Anm. 1, 31, 38, 46.

19
[ 65-45-2 ]
[ 19932-85-5 ]

References: [1]Synthesis,2001,p. 541 - 543.

20
[ 19932-85-5 ]
[ 74-88-4 ]
[ 67927-44-0 ]

Yield	Reaction Conditions	Operation in experiment
79%	With potassium carbonate; In acetone; at 20℃; for 4h;	Example 3: Scheme B2; To a solution of B2.1 (1 equiv., 23 mmol, 5.0 g) in acetone (230 ml) were successively added potassium carbonate (1.5 equiv., 35 mmol, 5.0 g) and iodomethane (1.2 equiv., <n="37"/>28 mmol, 4.0 g); the mixture was stirred at room temperature for 4 h. The acetone solvent was partially concentrated under reduced pressure; this mixture was poured on a IN aqueous HCl solution, filtered and successively washed with water, isopropanol and isopropyl ether, affording a pink powder B2.2 (4.22 g, yield = 79%, purity (LC) = 99%).
	With potassium carbonate; In acetone; at 80℃; for 3h;	Step 1: 6-bromo-3-methyl-1, 3-benzoxazol-2(3H)-one A mixture of <strong>[19932-85-5]6-bromo-1,3-benzoxazol-2(3H)-one</strong> (Aldrich, catNo.697036: 0.32 g, 1.5 mmol), methyl iodide (0.28 mL, 4.5 mmol) and potassium carbonate (210 mg, 1.5 mmol) in acetone (3 mL) was heated to 80 C. and stirred for 3 h. The reaction mixture was cooled to room temperature then diluted with water and extracted with EtOAc. The combined extracts were dried over Na2SO4, filtered and concentrated. The residue was used in the next step without further purification. LC-MS calculated for C8H7BrNO2 (M+H)+: m/z=228.0. found 227.9.

References: [1]Patent: WO2008/37784,2008,A1 .Location in patent: Page/Page column 35-36.
[2]Patent: US2016/289238,2016,A1 .Location in patent: Paragraph 0322; 0323.
[3]ChemMedChem,2018,vol. 13,p. 2522 - 2529.

21
[ 19932-85-5 ]
[ 113922-52-4 ]

References: [1]Chemistry of Heterocyclic Compounds,1987,vol. 23,p. 1024 - 1026.
Khimiya Geterotsiklicheskikh Soedinenii,1987,p. 1277 - 1279.

22
[ 19932-85-5 ]
[ 113922-50-2 ]

References: [1]Chemistry of Heterocyclic Compounds,1987,vol. 23,p. 1024 - 1026.
Khimiya Geterotsiklicheskikh Soedinenii,1987,p. 1277 - 1279.

23
[ 89-73-6 ]
[ 19932-85-5 ]

References: [1]Przemysl Chemiczny,1958,vol. 37,p. 418,419.
Chem.Abstr.,1959,p. 5246.

24
[ 95-55-6 ]
[ 19932-85-5 ]

References: [1]Journal fur praktische Chemie (Leipzig 1954),1888,vol. <2> 37,p. 28 Anm. 1, 31, 38, 46.

25
[ 19932-85-5 ]
[ 13610-73-6 ]

References: [1]Journal fur praktische Chemie (Leipzig 1954),1966,vol. 33,p. 130 - 138.

26
[ 19932-85-5 ]
[ 13610-71-4 ]

References: [1]Journal fur praktische Chemie (Leipzig 1954),1966,vol. 33,p. 130 - 138.

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[ 19932-85-5 ]
[ 13610-61-2 ]

References: [1]Journal fur praktische Chemie (Leipzig 1954),1966,vol. 33,p. 130 - 138.

28
[ 19932-85-5 ]
[ 98556-62-8 ]

References: [1]Patent: US6372933,2002,B1 .Location in patent: Page column 6.

29
[ 19932-85-5 ]
[ 76-83-5 ]
[ 312537-44-3 ]

Yield	Reaction Conditions	Operation in experiment
91%	With triethylamine; In dichloromethane; at 20℃; for 18h;	To a solution of 6-bromo-3H-benzoxazol-2-one (15 g; ca. 0.07 mol, containing 8-9% 3H-benzooxazol-2-one) and triethylamine (11.1 mL, 0.08 mol) in DCM (250 mL) was added trityl chloride (21.5 g, 0.08 mol). The solution was stirred at room temperature for 18 h and was then washed with distilled water (3×250 mL), brine (250 mL) and dried (MgSO4), filtered and evaporated to give an off-white colored solid. The product was dissolved in refluxing EtOAc then allowed to cool to room temperature with constant stirring for several hours. The solids were collected (21.16 g) and the filtrate was concentrated until precipitation occurred, re-heated (reflux) for several hours and allowed to cool with stirring to encourage a second crystallization (7.88 g). NMR and HPLC indicated the product (29.04 g, 91%) was very clean.
89%	With triethylamine; In dichloromethane; at 20℃;	To a solution of XXXV-2b (500 mg, 2.97 mmol) in dry DCM (20 mL) was added TEA (360 mg, 3.56 mmol) and Trt-Cl (992 mg, 3.56 mmol). The mixture was stuffed overnight at rt, then poured into water, extracted with DCM (50 mLx3). The combined organic layer was washed with brine, dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was purified by column chromatography on silica gel (PE/EA=10/1) to afford XXXV-3b (1.2 g, 89% yield).
77%	With NaH; In N,N-dimethyl-formamide;	EXAMPLE 121 6-Bromo-3-trityl-3 H-benzooxazol-2-one 6-Bromo-3H-benzooxazol-2-one (0.165 g, 0.77 mmol) was added portionwise into a 0 C. suspension of NaH (44.8 mg, 1 mmol, 55%) in dry DMF (4 ml). After 1 hour stirring at room temperature, a solution of triphenylmethylchloride (0.24 g, 0.85 mmol) in DMF (0.5 ml) was added. The reaction mixture was stirred 1 hour at room temperature then quenched with H2O (15 ml). The aqueous phase was extracted with ethyl acetate, the combined organic phases were washed with H2O and brine, dried over Na2SO4 and concentrated to provide 6-bromo-3-trityl-3H-benzooxazol-2-one (0.27 g, 77%) as a beige solid, MS: Mm/e=457.1 (M+H+).

	With triethylamine; In dichloromethane; at 20℃; for 18h;	To a solution of 6-bromo-3H-benzoxazol-2-one (15 g; ca. 0.07 mol, containing 8-9% 3H-benzooxazol-2-one) and triethylamine (11.1 mL, 0.08 mol) in DCM (250 mL) was added trityl chloride (21.5 g, 0.08 mol). The solution was stirred at room temperature for 18 h and was then washed with distilled water (3 x 250 mL), brine (250 mL) and dried (MgSO4), filtered and evaporated to give an off-white colored solid. The product was dissolved in refluxing EtOAc then allowed to cool to room temperature with constant stirring for several hours. The solids were collected (21.16 g) and the filtrate was concentrated until precipitation occurred, re-heated (reflux) for several hours and allowed to cool with stirring to encourage a second crystallization (7.88 g).
2.0 g	With triethylamine; In dichloromethane; for 1.16667h;	[0156j Triethylamine (0.72 g, 1.0 mL, 7.1 mmol) was added to a stirring a mixture of 6- bromo-2benzoxazilinone (0.89 g, 4.2 mmol) and trityichioride (1.21 g, 4.4 mmol) in CH2C12 (10 mL) for a period of 10 mm. The reaction was monitored by TLC (silica gel) and concentrated after 1 h. The concentrate was diluted with water and sonicated to form a heterogeneous solution. The resulting off-white solid was suction filtered and dried to provide 1 -trityl-6-bromo-2- benzoxazilinone (2.0 g). LCMS: rt 9.45 mm (A), purity 96 %, MS (mle) 456 (MHj.

References: [1]Patent: US2008/138413,2008,A1 .Location in patent: Page/Page column 22.
[2]Patent: WO2015/153683,2015,A1 .Location in patent: Paragraph 0951.
[3]Patent: US2001/47031,2001,A1 .
[4]Patent: WO2006/86705,2006,A1 .Location in patent: Page/Page column 84.
[5]Patent: WO2015/157093,2015,A1 .Location in patent: Paragraph 0156.

30
[ 59-49-4 ]
[ 77-48-5 ]
[ 19932-85-5 ]

Yield	Reaction Conditions	Operation in experiment
	With trifluorormethanesulfonic acid; In dichloromethane; ethyl acetate;	EXAMPLE 251A 6-bromo-1,3-benzoxazol-2(3H)-one A mixture of 2-benzoxazolinone (3.00 g, 22.2 mmol), 1,3-dibromo-5,5-dimethylhydantoin (3.49 g, 12.2 mmol), and trifluoromethanesulfonic acid (5.00 g, 33.3 mmol) in dichloromethane (100 mL) at room temperature was protected from light, stirred for 1 hour, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 50% ethyl acetate/hexanes to provide the desired product.
	With trifluorormethanesulfonic acid; In dichloromethane; ethyl acetate;	Example 251A 6-bromo-1,3-benzoxazol-2(3H)-one A mixture of 2-benzoxazolinone (3.00 g, 22.2 mmol), 1,3-dibromo-5,5-dimethylhydantoin (3.49 g, 12.2 mmol), and trifluoromethanesulfonic acid (5.00 g, 33.3 mmol) in dichloromethane (100 mL) at room temperature was protected from light, stirred for 1 hour, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 50% ethyl acetate/hexanes to provide the desired product.

References: [1]Patent: US2002/55631,2002,A1 .
[2]Patent: US2002/86887,2002,A1 .

31
[ 19932-85-5 ]
[ 544-92-3 ]
[ 98556-62-8 ]

Yield	Reaction Conditions	Operation in experiment
	In N,N-dimethyl-formamide; at 175℃; for 3h;	A mixture of 6-bromo-3H- benzooxazol-2-one (47) (400 mg, 1.87 mmol, 1 eq), copper cyanide (3.3 g, 37 mmol, 20 eq), in DMF( 10 ml) was stirred at 175 C for 3 hours. The reaction mixture was diluted with ethyl acetate, filtered to remove the precipitated solid material, and the organic phase was washed with water, purified by flash chromatography to give 2-oxo-2,3-dihydro- benzooxazole-6-carbonitrile (48).

References: [1]Patent: WO2007/22257,2007,A2 .Location in patent: Page/Page column 82.

32
[ 19932-85-5 ]
[ 54903-15-0 ]

Yield	Reaction Conditions	Operation in experiment
0.6402 g (91%)	With n-butyllithium; sec.-butyllithium; In tetrahydrofuran; N-methyl-acetamide; methanol; hexane; cyclohexane; water;	2-Oxo-2,3-dihydro-benzooxazole-6-carbaldehyde A solution of 6-bromo-3H-benzooxazol-2-one (0.9236 g, 4.31 micromoles) in anhydrous tetrahydrofuran (25 mL) and dimethylformamide (3 mL) under nitrogen was cooled to -78 C. before addition of n-butyllithium (2.5M in hexane) (3.8 mL, 2.2 equiv). After stirring for 10 min at -78 C., 24 mL of sec-butyllithium (1.4 M in cyclohexane, 8 equiv) was added. The reaction was stirred while slowly warming to -40 C. When this temperature was reached, the reaction was quenched by addition of methanol. The reaction mixture was concentrated in vacuo and water was added. The aqueous layer was acidified with 1N HCl (ca. pH 5) and extracted with ethyl acetate (3*50 mL), dried over sodium sulfate, filtered and concentrated to give the product, 0.6402 g (91%). MS (ESI) 164 (MH)+. 1H NMR (400 MHz, DMSO-d6) δ 9.90 (1H, s), 7.79 (1H, d, J=8.0 Hz), 7.74 (1H, s), 7.28 (1H, d, J=8.0 Hz).

References: [1]Patent: US2004/204397,2004,A1 .
[2]Patent: EP2592077,2013,A1 .
[3]Patent: WO2013/68552,2013,A1 .
[4]Patent: WO2013/68554,2013,A1 .

33
[ 4746-97-8 ]
[ 19932-85-5 ]
[ 75-16-1 ]
[ 598-30-1 ]
C₁₃H₁₃NO₄ [ No CAS ]
6-(8-hydroxy-1,4-dioxaspiro[4.5]dec-8-yl)-3H-benzoxazol-2-one [ No CAS ]

References: [1]Patent: EP1251128,2002,A1 .Location in patent: Page 38.

34
[ 4746-97-8 ]
[ 19932-85-5 ]
C₁₃H₁₃NO₄ [ No CAS ]
6-(8-hydroxy-1,4-dioxaspiro[4.5]dec-8-yl)-3H-benzoxazol-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Step 2: Bromide 1 (12.8 g, 59.6 mmol) was dissolved in anhydrous THF (220 mL), and the solution was cooled to ?78 C. Solutions of MeMgBr (21.9 mL of a 3.0 M solution in Et2O, 65.6 mmol), sec-BuLi (50.4 mL of a 1.3 M solution in cyclohexane, 65.6 mmol), and 1,4-Cyclohexanedione mono-ethylene ketal (11.2 g, 71.5 mmol) in anhydrous THF (10 mL) were added sequentially at 30-minute intervals. After the final addition, the reaction mixture was allowed to warm to room temperature. The reaction was quenched by the addition of 1N HCl (25 mL). The reaction mixture was diluted with EtOAc (500 mL), washed with saturated NaCl (250 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure to provide a mixture of 2 and 3, as a brown oil.

References: [1]Patent: US2003/236252,2003,A1 .Location in patent: Page 14.

35
[ 19932-85-5 ]
[ 1692-25-7 ]
[ 1194450-65-1 ]

Yield	Reaction Conditions	Operation in experiment
23%	With tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water;Inert atmosphere; Reflux;	General procedure: Heteroarylboronic acid (1.3 equivalents), aryl bromide (1 equivalent), and tetrakis(triphenylphosphine) palladium(0) (5mol %) were suspended in DME to give a 0.07-0.1M solution of boronic acid under nitrogen atmosphere. A 0.5M aqueous solution of sodium carbonate (6 equivalents) was added. The mixture was refluxed for 3.5-14h, cooled to room temperature, diluted with water and extracted several times with ethyl acetate. The combined extracts were dried over anhydrous MgSO4, concentrated and purified by flash chromatography and were if necessary recrystallized.

References: [1]European Journal of Medicinal Chemistry,2015,vol. 90,p. 788 - 796.

Historical Records

Technical Information

• Acyl Group Substitution • Alkyl Halide Occurrence • Baeyer-Villiger Oxidation • Barbier Coupling Reaction • Baylis-Hillman Reaction • Benzylic Oxidation • Birch Reduction • Blanc Chloromethylation • Bucherer-Bergs Reaction • Chan-Lam Coupling Reaction • Clemmensen Reduction • Complex Metal Hydride Reductions • Corey-Bakshi-Shibata (CBS) Reduction • Corey-Chaykovsky Reaction • Fischer Indole Synthesis • Friedel-Crafts Reaction • General Reactivity • Grignard Reaction • Henry Nitroaldol Reaction • Hiyama Cross-Coupling Reaction • Horner-Wadsworth-Emmons Reaction • Hydride Reductions • Hydrogenolysis of Benzyl Ether • Kinetics of Alkyl Halides • Kumada Cross-Coupling Reaction • Lawesson's Reagent • Leuckart-Wallach Reaction • McMurry Coupling • Meerwein-Ponndorf-Verley Reduction • Passerini Reaction • Paternò-Büchi Reaction • Petasis Reaction • Peterson Olefination • Pictet-Spengler Tetrahydroisoquinoline Synthesis • Preparation of Aldehydes and Ketones • Preparation of Alkylbenzene • Preparation of Amines • Prins Reaction • Reactions of Aldehydes and Ketones • Reactions of Alkyl Halides with Reducing Metals • Reactions of Amines • Reactions of Benzene and Substituted Benzenes • Reactions of Dihalides • Reformatsky Reaction • Robinson Annulation • Schlosser Modification of the Wittig Reaction • Schmidt Reaction • Specialized Acylation Reagents-Carbodiimides and Related Reagents • Specialized Acylation Reagents-Ketenes • Stille Coupling • Stobbe Condensation • Substitution and Elimination Reactions of Alkyl Halides • Suzuki Coupling • Tebbe Olefination • Ugi Reaction • Vilsmeier-Haack Reaction • Wittig Reaction • Wolff-Kishner Reduction

Related Functional Groups of
[ 19932-85-5 ]

Bromides

A157614 [14733-73-4]

5-Bromobenzo[d]oxazol-2(3H)-one

Similarity: 1.00

A150964 [871367-14-5]

7-Bromobenzo[d]oxazol-2(3H)-one

Similarity: 0.85

A163839 [169303-80-4]

tert-Butyl (2-bromo-5-methoxyphenyl)carbamate

Similarity: 0.83

A206950 [67927-44-0]

6-Bromo-3-methylbenzo[d]oxazol-2(3H)-one

Similarity: 0.83

A117968 [401811-77-6]

tert-Butyl (5-bromobenzo[d][1,3]dioxol-4-yl)carbamate

Similarity: 0.78

Amides

A157614 [14733-73-4]

5-Bromobenzo[d]oxazol-2(3H)-one

Similarity: 1.00

A150964 [871367-14-5]

7-Bromobenzo[d]oxazol-2(3H)-one

Similarity: 0.85

A163839 [169303-80-4]

tert-Butyl (2-bromo-5-methoxyphenyl)carbamate

Similarity: 0.83

A206950 [67927-44-0]

6-Bromo-3-methylbenzo[d]oxazol-2(3H)-one

Similarity: 0.83

A383012 [81282-60-2]

7-Aminobenzo[d]oxazol-2(3H)-one

Similarity: 0.80

Related Parent Nucleus of
[ 19932-85-5 ]

Benzoxazoles

A157614 [14733-73-4]

5-Bromobenzo[d]oxazol-2(3H)-one

Similarity: 1.00

A150964 [871367-14-5]

7-Bromobenzo[d]oxazol-2(3H)-one

Similarity: 0.85

A206950 [67927-44-0]

6-Bromo-3-methylbenzo[d]oxazol-2(3H)-one

Similarity: 0.83

A383012 [81282-60-2]

7-Aminobenzo[d]oxazol-2(3H)-one

Similarity: 0.80

A107429 [5579-85-1]

6-Bromo-5-chlorobenzo[d]oxazol-2(3H)-one

Similarity: 0.74

Precautionary Statements-General
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P378
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P337 + P313	IF eye irritation persists: Get medical advice/attention.
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Physical hazards
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H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
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Environmental hazards
Code	Phrase
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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

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CAS No.: 19932-85-5

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