1,3-Dihydro-1-(methylsulfonyl)-2H-benzimidazole-2-one | 711-39-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 1,3-Dihydro-1-(methylsulfonyl)-2H-benzimidazole-2-one
• 英文别名: 1-methanesulfonyl-1,3-dihydro-benzoimidazol-2-one；1-Methansulfonyl-2-oxo-benzimidazolin；3-methylsulfonyl-1H-benzimidazol-2-one
• CAS: 711-39-7
• 化学式: C₈H₈N₂O₃S
• 分子量: 212.229
• InChiKey: FEHRUNJVCNMLTR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  74.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-羟基苯并咪唑 在 4-二甲氨基吡啶 、 potassium carbonate 、 异丙胺 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 1.66h， 生成 1,3-Dihydro-1-(methylsulfonyl)-2H-benzimidazole-2-one
  参考文献：
  名称：

  Regiospecific Functionalization of 1,3-Dihydro-2H-benzimidazol-2-one and Structurally Related Cyclic Urea Derivatives

  摘要：

  Methods for selectively protecting one of the degenerate nitrogen atoms of the cyclic urea derivatives 1,3-dihydro-2H-benzimidazol-2-one (6a), 1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (11), 1,3-dihydro-2H-imidazo[4,5-b]quinolin-2-ones (20), 1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (22), and 1,3-dihydro-4-phenyl-2H-imidazol-2-one (27) were developed. Heating these cyclic ureas with ethyl 2-pyridyl carbonate in the presence of a base in CH3CN at reflux or DMF at 100 degrees C cleanly provided the monoethoxycarbonyl derivatives 7a, 12, 21, 23, and 28, respectively. Alternatively, treatment of 6a with an excess of diethyl pyrocarbonate or di-tert-butyl dicarbonate afforded the bis-alkoxycarbonyl derivatives 8a and 8b, respectively, which underwent disproportionation to 7a and 7b upon heating with 1 mol equiv of 6a and K2CO3 in CH3CN at reflux. The regiochemistry of the introduction of alkoxycarbonyl groups to benzimidazol-2-one derivatives was not significantly influenced by an electron-withdrawing (CF3, 6b) or an electron-donating (OCH3, 6c) substituent at C-5 of the heterocyclic ring. However, the reaction was found to be sensitive to steric factors since a chlorine substituent ortho to one of the urea N atoms (6e) completely directed the alkoxycarbonyl moiety to the less sterically encumbered N atom, affording a single product (7f, 7g). Alkylation of 7a-g proceeded efficiently to provide products 10a-10ag after removal of the protecting group. Halogenation of monoprotected benzimidazol-2-one 7a occurred regiospecifically to give the monohalo derivatives 7h, 7i, and 7k, the identity of which were readily established from the characteristic chemical shift and spin coupling pattern in their 1H NMR spectra. A protecting group interchange strategy that took advantage of the distinctive chemical reactivities of the EtO(2)C and t-BuO(2)C protecting groups toward isopropylamine was developed that provided access to the isomerically substituted series of monohalo, mono-N-alkylated benzimidazol-2-ones 71 and 7m. The efficient derivatization of the unprotected N atom of these monoprotected cyclic urea derivatives was accomplished by treating with activated and unactivated halides in the. presence of K2CO3 or exposure to alcohols under Mitsunobu conditions. In several cases, mixtures of O- and N-alkylated products were produced which were readily separated by chromatography. Alkylation of 7h with activated halides, using K2CO3 in CH3CN at reflux, occurred without protecting group equilibration; however, a mixture of isomeric alkylated products was obtained when 7h was heated at 110 degrees C in DMF with cyclohexylmethyl bromide in the presence of K2CO3 as the base. Derivatization of 7h under Mitsunobu reaction conditions proceeded with retention of the topological substituent relationships. Subsequent removal of the alkoxycarbonyl moiety afforded monoalkylated cyclic urea derivatives.

  DOI：

  10.1021/jo00111a014

文献信息

• COMPOUNDS TO TREAT AMYLOIDOSIS AND PREVENT DEATH OF BETA-CELLS IN TYPE 2 DIABETES MELLITUS
  申请人：Zolotoy Alexander B.

  公开号：US20080255091A1

  公开（公告）日：2008-10-16

  The invention discloses aromatic amides and sulfonates to treat or prevent type 2 diabetes mellitus (T2DM), the pathological consequences of T2DM, to inhibit amyloidosis or to prevent death of β-cells of the pancreas.

  本发明揭示了用于治疗或预防2型糖尿病（T2DM）、T2DM的病理后果、抑制淀粉样变或预防胰腺β细胞死亡的芳香族酰胺和磺酸盐。
• PYRIMIDIN-4-ONE DERIVATIVES AND THEIR USE AS P38 KINASE MODULATORS
  申请人：Pharmacia Corporation

  公开号：EP1753731A2

  公开（公告）日：2007-02-21
• INHIBITORS OF SERINE PALMITOYLTRANSFERASE
  申请人：Pfizer Products Inc.

  公开号：EP2121656A1

  公开（公告）日：2009-11-25
• [EN] SUBSTITUTED PYRIMIDINONES<br/>[FR] PYRIMIDINONES SUBSTITUEES
  申请人：PHARMACIA CORP

  公开号：WO2004087677A2

  公开（公告）日：2004-10-14

  Disclosed are compounds Formula I and pharmaceutically acceptable salts thereof, wherein R1, R2, R4, and R5 are defined herein. These compounds are useful for treating diseases and conditions caused or exacerbated by unregulated p38 MAP Kinase and/or TNF activity. Pharmaceutical compositions containing the compounds, methods of preparing the compounds and methods of treatment using the compounds are also disclosed.
• [EN] INHIBITORS OF SERINE PALMITOYLTRANSFERASE<br/>[FR] INHIBITEURS DE LA SÉRINE PALMITOYL-TRANSFÉRASE
  申请人：PFIZER PROD INC

  公开号：WO2008084300A1

  公开（公告）日：2008-07-17

  [EN] This invention provides compounds of the formula (I) useful in the inhibition or modulation of serine palmitoyl transferase and their use in methods of treatment or amelioration of type 2 diabetes, type 1 diabetes, insulin resistance, the effects of obesity, metabolic syndrome (sometimes referred to as Syndrome X), impaired glucose tolerance, Cushing's disease, cardiovascular disease, prothrombotic conditions, myocardial infarction, hypertension, congestive heart failure, cardiomyopathy, atherosclerosis, dyslipidemia, sepsis, liver damage, retinal degenerative disorders, cachexia, emphysema, hepatitis C infections, HIV infections and inflammatory disorders and useful in methods for raising HDL plasma levels in a mammal. The compounds of this invention can also be used to prevent damage or loss of pancreatic islet beta cells (such as in the case of pancreatic beta cell apoptosis, including those related to insulin-dependent diabetes mellitus).
  [FR] La présente invention concerne des composés de formule (I) utilisables pour l'inhibition ou la modulation de la sérine palmitoyl-transférase et leur utilisation dans des procédés de traitement ou d'amélioration du diabète de type 2, du diabète de type 1, de l'insulinorésistance, des effets de l'obésité, du syndrome métabolique (parfois appelé syndrome X), de l'insuffisance de la tolérance au glucose, de la maladie de Cushing, d'une maladie cardiovasculaire, des états prothrombotiques, de l'infarctus du myocarde, de l'hypertension, de l'insuffisance cardiaque congestive, de la cardiomyopathie, de l'athérosclérose, de la dyslipidémie, de la septicémie, de l'atteinte hépatique, des troubles de dégénérescence rétinienne, de la cachexie, de l'emphysème, des infections d'hépatite C, des infections par le HIV et des troubles inflammatoires, ainsi que leur utilisation dans des procédés permettant d'augmenter les taux plasmatiques de HDL chez un mammifère. L'invention concerne des composés qui peuvent également être utilisés pour éviter les lésions ou la perte des cellules bêta des îlots pancréatiques (telles que dans le cas de l'apoptose des cellules bêta pancréatiques, y compris celles liées au diabète sucré insulino-dépendant).