2,5-Dichlorobenzooxazole

Base Information

• Chemical Name: 2,5-Dichlorobenzooxazole
• CAS No.: 3621-81-6
• Molecular Formula: C7H3Cl2NO
• Molecular Weight: 188.013
• Hs Code.: 2934999090
• DSSTox Substance ID: DTXSID40439214
• Wikidata: Q72465526
• Mol file: 3621-81-6.mol

Synonyms:2,5-dichlorobenzooxazole;3621-81-6;2,5-dichloro-1,3-benzoxazole;2,5-dichlorobenzo[d]oxazole;2,5-DICHLOROBENZOXAZOLE;BENZOXAZOLE, 2,5-DICHLORO-;2,5-Dichloro-benzooxazole;MFCD09264312;SCHEMBL1672481;MK4305OEth(1/4)aIa2;DTXSID40439214;JOXBFDPBVQGJOJ-UHFFFAOYSA-N;BCP28343;STK502936;AKOS000321587;AC-7217;CS-W019777;PB26446;DS-10866;A6278;AM20040279;BB 0240847;FT-0647638;EN300-330992

Chemical Property of 2,5-Dichlorobenzooxazole

Chemical Property:

• Vapor Pressure: 0.052mmHg at 25°C
• Melting Point: 44-46 °C
• Refractive Index: 1.636
• Boiling Point: 242.867 °C at 760 mmHg
• PKA: -1.40±0.10(Predicted)
• Flash Point: 100.683 °C
• PSA: 26.03000
• Density: 1.523 g/cm³
• LogP: 3.13460
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• XLogP3: 3.8
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 0
• Exact Mass: 186.9591691
• Heavy Atom Count: 11
• Complexity: 155

Purity/Quality:

99% ^*data from raw suppliers

2,5-Dichloro-1,3-benzoxazole ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: C1=CC2=C(C=C1Cl)N=C(O2)Cl

Technology Process of 2,5-Dichlorobenzooxazole

There total 3 articles about 2,5-Dichlorobenzooxazole which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 91.0%

5-chloro-2-mercaptobenzoxazole (22876-19-3) → 2,5-dichloro-1,3-benzoxazole (3621-81-6)

Guidance literature:

With thionyl chloride; N,N-dimethyl-formamide; In dichloromethane; at 5 - 20 ℃; for 4h;

Reference yield: 30.0%

5-chlorobenzo[d]oxazole-2(3H)-thione (22876-19-3) → 2,5-dichloro-1,3-benzoxazole (3621-81-6)

Guidance literature:

With phosphorus pentachloride; trichlorophosphate; at 95 - 100 ℃; for 2.5h;

DOI:10.1021/jo952101z

Reference yield:

5-chloro-2-mercaptobenzoxazole (22876-19-3) + oxalyl dichloride (79-37-8) → 2,5-dichloro-1,3-benzoxazole (3621-81-6)

Guidance literature:

In dichloromethane; N,N-dimethyl-formamide; at 20 - 25 ℃; for 1.75h;

DOI:10.1021/op1002853

upstream raw materials:

5-chlorobenzo[d]oxazole-2(3H)-thione

5-chloro-2-mercaptobenzoxazole

oxalyl dichloride

Downstream raw materials:

methyl 5-chloro-1,3-benzoxazole-2-carboxylate

4-[N-methyl-N-(5-chloro-2-benzoxazolyl)amino]phenol

C₁₃H₁₆ClN₃O*C₁₈H₁₄O₈

C₁₃H₁₆ClN₃O*C₁₈H₁₄O₈

Refernces

Discovery of the dual orexin receptor antagonist [(7 R)-4-(5-chloro-1,3- benzoxazol-2-yl)-7-methyl-1,4-diazepan-1-yl][5-methyl-2-(2 H -1,2,3-triazol-2-yl)phenyl]methanone (MK-4305) for the treatment of insomnia

10.1021/jm100541c

The research focuses on the development of a dual orexin receptor antagonist for treating insomnia. The study began with compound 4, a diazepane-based orexin receptor antagonist, which had excellent brain penetration and potency but suffered from high clearance and low bioavailability. Efforts to improve its pharmacokinetics led to the identification of compound 10 with a 7-methyl substitution on the diazepane core, which displayed good potency, improved pharmacokinetics, and excellent in vivo efficacy. However, compound 10 formed reactive metabolites in microsomal incubations. A mechanistic hypothesis and an in vitro assay to assess bioactivation led to the replacement of the fluoroquinazoline ring of 10 with a chlorobenzoxazole to provide 3 (MK-4305), a potent dual orexin receptor antagonist that is currently being tested in phase III clinical trials for the treatment of primary insomnia. Chemicals such as 2-(2H-1,2,3-triazol-2-yl)-5-methylbenzoic acid, 2,5-dichloro-1,3-benzoxazole, and various diazepane cores played crucial roles in the synthesis and optimization of these compounds.