2-methoxymethylcyclopropylcarbonyl chloride | 870809-45-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-methoxymethylcyclopropylcarbonyl chloride
• 英文别名: 2-(methoxymethyl)cyclopropane-1-carbonyl chloride
• CAS: 870809-45-3
• 化学式: C₆H₉ClO₂
• 分子量: 148.589
• InChiKey: MJBVZGNDQGMZCS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  9
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-methoxymethylcyclopropylcarbonyl chloride 在 potassium permanganate 、 copper(l) iodide 、 bis(triphenylphosphine) palladium (Il) acetate 、 水 、 sodium carbonate 、 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 生成
  参考文献：
  名称：

  Optimization of 2-phenyl-pyrimidine-4-carboxamides towards potent, orally bioavailable and selective P2Y12 antagonists for inhibition of platelet aggregation

  摘要：

  2-Phenyl-pyrimidine-4-carboxamide analogs were identified as P2Y12 antagonists. Optimization of the carbon-linked or nitrogen-linked substituent at the 6-position of the pyrimidine ring provided compounds with excellent ex vivo potency in the platelet aggregation assay in human plasma. Compound 23u met the objectives for activity, selectivity and ADMET properties.

  DOI：

  10.1016/j.bmcl.2014.06.070

文献信息

• [EN] OCULOSELECTIVE DRUGS AND PRODRUGS<br/>[FR] MEDICAMENTS ET PROMEDICAMENTS OCULOSELECTIFS
  申请人：OTHERA PHARMACEUTICALS INC

  公开号：WO2005115375A1

  公开（公告）日：2005-12-08

  Compounds of the following formula are disclosed: wherein R1 and R2 are each independently H, W, or a phenoxyl protecting group; and R4is H or W, provided that at least one of R1, R2, and R4 is W; R3 is hydrogen, straight chain or branched C1-C10 alkyl, cycloalkyl, amino, C1-C10 alkoxy, -NHC(=O)Ra, or -C(=O)N(H)Ra; Ra is alkyl, aryl, or heterocyclyl; Z is -0-, -O(C=O)-, or NH(C=O)-, wherein when Z is -0-, R5 is H, straight chain or branched C1-C10 alkyl, cycloalkyl, cycloalkyl substituted with at least one straight or branched C1-C10 alkyl, CI-Clo alkoxyalkyl, amino, benzyl, tetrahydrofuranyl, dihydrofuranyl, furanyl, morpholinyl, piperidinyl, tetrahydropyranyl, dioxolanyl, 2,2-dimethyl dioxolanyl, dioxanyl, pyrrolyl, pyrrolsdinyl, tetrahydrooxazolyl, dihydrooxazolyl, phenyl, or phenyl substituted with CI-Clo alkyl, C1-C10 alkoxy, or halo; and W is:, wherein each R6 is independently H, straight chain or branched C1-C10 alkyl, or straight chain or branched Cl-C10 alkoxyalkyl; and R7 is alkyl, cycloalkyl, aryl, or aralkyl; and wherein when Z is -O(C=O)-, R5 is straight chain or branched C1-C10 alkyl, cycloalkyl, cycloalkyl substituted with at least one straight or branched C1-C10 alkyl, CI-CIO alkoxyalkyl, amino, benzyl, tetrahydrofuranyl, dihydrofuranyl, furanyl, morpholinyl, piperidinyl, tetrahydropyranyl, dioxolanyl, 2,2-dimethyl dioxolanyl, dioxanyl, pyrrolyl, pyrrolidinyl, tetrahydrooxazolyl, dihydrooxazolyl, phenyl, or phenyl substituted with Cl-C10 alkyl, C1-C10 alkoxy, or halo; and W is: , wherein each R6 is independently H, straight chain or branched CI-C to alkyl, or straight chain or branched C,-C to alkoxyalkyl; and R7 is alkyl, cycloalkyl, aryl, or aralkyl; and wherein when Z is-NH(C=O)-, R5 is straight chain or branched C1 -C10 alkyl, cycloalkyl, cycloalkyl substituted with at least one straight or branched C1-C10 alkyl, CI-CIO alkoxyalkyl, amino, benzyl, tetrahydrofuranyl, dihydrofuranyl, furanyl, morpholinyl, piperidinyl, tetrahydropyranyl, &oxolanyl, 2,2-dimethyl dioxolanyl, dioxanyl, pyrrolyl, pyrrolidinyl, tetrahydrooxazolyl, dihydrooxazolyl, phenyl, or phenyl substituted with C1-C10 alkyl, C1-C10 alkoxy, or halo; and W is: ; wherein each R6 is independently H, straight chain or branched C1 -C to alkyl, or straight chain or branched C,-Clo alkoxyalkyl. Methods of preparing the compounds, pharmaceutical compositions comprising the compounds, and methods of treating patients by administration of the pharmaceutical compositions, are also disclosed.

  公开了以下式子的化合物：其中R1和R2分别独立地为H、W或苯氧基保护基；R4为H或W，但至少其中一个为W；R3为氢、直链或支链C1-C10烷基、环烷基、氨基、C1-C10烷氧基、-NHC（=O）Ra或-C（=O）N（H）Ra；Ra为烷基、芳基或杂环基；Z为-0-、-O（C=O）-或NH（C=O）-，其中当Z为-0-时，R5为H、直链或支链C1-C10烷基、环烷基、至少含有一个直链或支链C1-C10烷基的环烷基、CI-Clo烷氧基烷基、氨基、苯甲基、四氢呋喃基、二氢呋喃基、呋喃基、吗啉基、哌啶基、四氢吡喃基、二氢二氧杂环基、2,2-二甲基二氧杂环基、二氧杂环基、吡咯基、吡咯啉基、四氢噁唑基、二氢噁唑基、苯基或被CI-Clo烷基、C1-C10烷氧基或卤素取代的苯基；W为：其中每个R6独立地为H、直链或支链C1-C10烷基或直链或支链Cl-C10烷氧基烷基；R7为烷基、环烷基、芳基或芳烷基；当Z为-O（C=O）-时，R5为直链或支链C1-C10烷基、环烷基、至少含有一个直链或支链C1-C10烷基的环烷基、CI-CIO烷氧基烷基、氨基、苯甲基、四氢呋喃基、二氢呋喃基、呋喃基、吗啉基、哌啶基、四氢吡喃基、二氢二氧杂环基、2,2-二甲基二氧杂环基、二氧杂环基、吡咯基、吡咯啉基、四氢噁唑基、二氢噁唑基、苯基或被CI-C10烷基、C1-C10烷氧基或卤素取代的苯基；W为：其中每个R6独立地为H、直链或支链CI-C to烷基或直链或支链C,-C to烷氧基烷基；R7为烷基、环烷基、芳基或芳烷基；当Z为-NH（C=O）-时，R5为直链或支链C1-C10烷基、环烷基、至少含有一个直链或支链C1-C10烷基的环烷基、CI-CIO烷氧基烷基、氨基、苯甲基、四氢呋喃基、二氢呋喃基、呋喃基、吗啉基、哌啶基、四氢吡喃基、二氢二氧杂环基、2,2-二甲基二氧杂环基、二氧杂环基、吡咯基、吡咯啉基、四氢噁唑基、二氢噁唑基、苯基或被C1-C10烷基、C1-C10烷氧基或卤素取代的苯基；W为：其中每个R6独立地为H、直链或支链C1-C to烷基或直链或支链C,-Clo烷氧基烷基。还公开了制备这些化合物的方法、包含这些化合物的药物组成物以及通过给患者给药这些药物组成物的治疗方法。
• Oculoselective Drugs and Prodrugs
  申请人：Matier L. William

  公开号：US20070254950A1

  公开（公告）日：2007-11-01

  Compounds of the following formula are disclosed: wherein R 1 and R 2 are each independently H, W, or a phenoxyl protecting group; and R 4 is H or W, provided that at least one of R 1 , R 2 , and R 4 is W; R 3 is hydrogen, straight chain or branched C 1 -C 10 alkyl, cycloalkyl, amino, C 1 -C 10 alkoxy, —NHC(═O)Ra, or —C(═O)N(H)R a ; R a is alkyl, aryl, or heterocyclyl; Z is -0-, —O(C═O)—, or NH(C═O)—, wherein when Z is -0-, R 5 is H, straight chain or branched C 1 -C 10 alkyl, cycloalkyl, cycloalkyl substituted with at least one straight or branched C 1 -C 10 alkyl, CI—Clo alkoxyalkyl, amino, benzyl, tetrahydrofuranyl, dihydrofuranyl, furanyl, morpholinyl, piperidinyl, tetrahydropyranyl, dioxolanyl, 2,2-dimethyl dioxolanyl, dioxanyl, pyrrolyl, pyrrolsdinyl, tetrahydrooxazolyl, dihydrooxazolyl, phenyl, or phenyl substituted with CI—Clo alkyl, C 1 -C 10 alkoxy, or halo; and W is: wherein each R 6 is independently H, straight chain or branched C 1 -C 10 alkyl, or straight chain or branched C 1 -C 10 alkoxyalkyl; and R 7 is alkyl, cycloalkyl, aryl, or aralkyl; and wherein when Z is —O(C═O)—, R 5 is straight chain or branched C 1 -C 10 alkyl, cycloalkyl, cycloalkyl substituted with at least one straight or branched C 1 -C 10 alkyl, CI—CIO alkoxyalkyl, amino, benzyl, tetrahydrofuranyl, dihydrofuranyl, furanyl, morpholinyl, piperidinyl, tetrahydropyranyl, dioxolanyl, 2,2-dimethyl dioxolanyl, dioxanyl, pyrrolyl, pyrrolidinyl, tetrahydrooxazolyl, dihydrooxazolyl, phenyl, or phenyl substituted with C 1 -C 10 alkyl, C 1 -C 10 alkoxy, or halo; and W is:, wherein each R6 is independently H, straight chain or branched CI—C to alkyl, or straight chain or branched C,—C to alkoxyalkyl; and R7 is alkyl, cycloalkyl, aryl, or aralkyl; and wherein when Z is —NH(C═O)—, R5 is straight chain or branched C 1 -C 10 alkyl, cycloalkyl, cycloalkyl substituted with at least one straight or branched C 1 -C 10 alkyl, CI—CIO alkoxyalkyl, amino, benzyl, tetrahydrofuranyl, dihydrofuranyl, furanyl, morpholinyl, piperidinyl, tetrahydropyranyl, & oxolanyl, 2,2-dimethyl dioxolanyl, dioxanyl, pyrrolyl, pyrrolidinyl, tetrahydrooxazolyl, dihydrooxazolyl, phenyl, or phenyl substituted with C 1 -C 10 alkyl, C 1 -C 10 alkoxy, or halo; and W is: wherein each R6 is independently H, straight chain or branched C1-C to alkyl, or straight chain or branched C,—Clo alkoxyalkyl. Methods of preparing the compounds, pharmaceutical compositions comprising the compounds, and methods of treating patients by administration of the pharmaceutical compositions, are also disclosed.

  公开了以下式子的化合物：其中R1和R2分别独立地为H，W或苯氧基保护基；而R4为H或W，但至少其中之一为W；R3为氢，直链或支链C1-C10烷基，环烷基，氨基，C1-C10烷氧基，—NHC（═O）Ra，或—C（═O）N（H）Ra；Ra为烷基，芳基或杂环基；Z为-0-，—O（C═O）—或NH（C═O）—，其中当Z为-0-时，R5为H，直链或支链C1-C10烷基，环烷基，至少有一个直链或支链C1-C10烷基替代的环烷基，CI-Clo烷氧基烷基，氨基，苄基，四氢呋喃基，二氢呋喃基，呋喃基，吗啉基，哌啶基，四氢吡喃基，二氢二氧杂环基，2,2-二甲基二氧杂环基，二氧杂环基，吡咯基，吡咯啉基，四氢噁唑基，二氢噁唑基，苯基，或带有CI-Clo烷基，C1-C10烷氧基或卤素替代的苯基；W为：其中每个R6独立地为H，直链或支链C1-C10烷基或直链或支链C1-C10烷氧基烷基；而R7为烷基，环烷基，芳基或芳基烷基；当Z为—O（C═O）—时，R5为直链或支链C1-C10烷基，环烷基，至少有一个直链或支链C1-C10烷基替代的环烷基，CI-Clo烷氧基烷基，氨基，苄基，四氢呋喃基，二氢呋喃基，呋喃基，吗啉基，哌啶基，四氢吡喃基，二氢二氧杂环基，2,2-二甲基二氧杂环基，二氧杂环基，吡咯基，吡咯啉基，四氢噁唑基，二氢噁唑基，苯基，或带有C1-C10烷基，C1-C10烷氧基或卤素替代的苯基；W为：其中每个R6独立地为H，直链或支链C1-C10烷基或直链或支链C1-C10烷氧基烷基；而R7为烷基，环烷基，芳基或芳基烷基；当Z为—NH（C═O）—时，R5为直链或支链C1-C10烷基，环烷基，至少有一个直链或支链C1-C10烷基替代的环烷基，CI-Clo烷氧基烷基，氨基，苄基，四氢呋喃基，二氢呋喃基，呋喃基，吗啉基，哌啶基，四氢吡喃基，二氢二氧杂环基，2,2-二甲基二氧杂环基，二氧杂环基，吡咯基，吡咯啉基，四氢噁唑基，二氢噁唑基，苯基，或带有C1-C10烷基，C1-C10烷氧基或卤素替代的苯基；W为：其中每个R6独立地为H，直链或支链C1-C10烷基或直链或支链C1-C10烷氧基烷基。还公开了制备这些化合物的方法，包括这些化合物的制药组合物以及通过给药这些制药组合物治疗患者的方法。
• OCULOSELECTIVE DRUGS AND PRODRUGS
  申请人：MATIER WILLIAM L.

  公开号：US20100179218A1

  公开（公告）日：2010-07-15

  Compounds of the following formula are disclosed: Methods of preparing the compounds, pharmaceutical compositions comprising the compounds, and methods of treating patients by administration of the pharmaceutical compositions are disclosed.

  以下公式的化合物已被披露：披露了制备这些化合物的方法，包括这些化合物的制药组合物和通过给患者用制药组合物治疗的方法。
• Oculoselective drugs and prodrugs
  申请人：Matier L. William

  公开号：US20060019955A1

  公开（公告）日：2006-01-26

  Compounds of the following formula are disclosed: wherein R 1 and R 2 are each independently H, W, or a phenoxyl protecting group; and R 4 is H or W, provided that at least one of R 1 , R 2 , and R 4 is W; R 3 is hydrogen, straight chain or branched C 1 -C 10 alkyl, cycloalkyl, amino, C 1 -C 10 alkoxy, —NHC(═O)R a , or —C(═O)N(H)R a ; R a is alkyl, aryl, or heterocyclyl; Z is —O—, —O(C═O)—, or —NH(C═O)—, wherein when Z is —O—, R 5 is H, straight chain or branched C 1 -C 10 alkyl, cycloalkyl, cycloalkyl substituted with at least one straight or branched C 1 -C 10 alkyl, C 1 -C 10 alkoxyalkyl, amino, benzyl, tetrahydrofuranyl, dihydrofuranyl, furanyl, morpholinyl, piperidinyl, tetrahydropyranyl, dioxolanyl, 2,2-dimethyl dioxolanyl, dioxanyl, pyrrolyl, pyrrolidinyl, tetrahydrooxazolyl, dihydrooxazolyl, phenyl, or phenyl substituted with C 1 -C 10 alkyl, C 1 -C 10 alkoxy, or halo; and W is: wherein each R 6 is independently H, straight chain or branched C 1 -C 10 alkyl, or straight chain or branched C 1 -C 10 alkoxyalkyl; and R 7 is alkyl, cycloalkyl, aryl, or aralkyl; and wherein when Z is —O(C═O)—, R 5 is straight chain or branched C 1 -C 10 alkyl, cycloalkyl, cycloalkyl substituted with at least one straight or branched C 1 -C 10 alkyl, C 1 -C 10 alkoxyalkyl, amino, benzyl, tetrahydrofuranyl, dihydrofuranyl, furanyl, morpholinyl, piperidinyl, tetrahydropyranyl, dioxolanyl, 2,2-dimethyl dioxolanyl, dioxanyl, pyrrolyl, pyrrolidinyl, tetrahydrooxazolyl, dihydrooxazolyl, phenyl, or phenyl substituted with C 1 -C 10 alkyl, C 1 -C 10 alkoxy, or halo; and W is: wherein each R 6 is independently H, straight chain or branched C 1 -C 10 alkyl, or straight chain or branched C 1 -C 10 alkoxyalkyl; and R 7 is alkyl, cycloalkyl, aryl, or aralkyl; and wherein when Z is —NH(C═O)—, R 5 is straight chain or branched C 1 -C 10 alkyl, cycloalkyl, cycloalkyl substituted with at least one straight or branched C 1 -C 10 alkyl, C 1 -C 10 alkoxyalkyl, amino, benzyl, tetrahydrofuranyl, dihydrofuranyl, furanyl, morpholinyl, piperidinyl, tetrahydropyranyl, dioxolanyl, 2,2-dimethyl dioxolanyl, dioxanyl, pyrrolyl, pyrrolidinyl, tetrahydrooxazolyl, dihydrooxazolyl, phenyl, or phenyl substituted with C 1 -C 10 alkyl, C 1 -C 10 alkoxy, or halo; and W is: wherein each R 6 is independently H, straight chain or branched C 1 -C 10 alkyl, or straight chain or branched C 1 -C 10 alkoxyalkyl. Methods of preparing the compounds, pharmaceutical compositions comprising the compounds, and methods of treating patients by administration of the pharmaceutical compositions, are also disclosed.

  公开了下式化合物： 其中 R 1 和 R 2 各自独立地为 H、W 或苯氧基保护基；以及 R 4 是 H 或 W，条件是 R 1 , R 2 和 R 4 为 W；R 3 是氢、直链或支链 C 1 -C 10 烷基、环烷基、氨基、C 1 -C 10 烷氧基、-NHC(═O)R a 或-C(═O)N(H)R a a ; R a 是烷基、芳基或杂环基； Z 是 -O-、-O(C═O)- 或 -NH(C═O)-，其中当 Z 是 -O- 时，R 5 是 H、直链或支链 C 1 -C 10 烷基、环烷基、被至少一个直链或支链 C 1 -C 10 烷基、环烷基、被至少一个直链或支链 1 -C 10 烷氧基烷基、氨基、苄基、四氢呋喃基、二氢呋喃基、呋喃基、吗啉基、哌啶基、四氢吡喃基、二氧戊环基、2,2-二甲基二氧戊环基、二氧杂环基、吡咯基、吡咯烷基、四氢恶唑基、二氢恶唑基、苯基或被 C 1 -C 10 烷基、C 1 -C 10 烷氧基，或卤代烃；W 是 其中每个 R 6 独立地为 H、直链或支链 C 1 -C 10 烷基，或直链或支链 C 1 -C 10 烷氧基烷基；以及 R 7 是烷基、环烷基、芳基或芳烷基；其中当 Z 是-O(C═O)-时，R 5 是直链或支链 C 1 -C 10 烷基、环烷基、被至少一个直链或支链 C 1 -C 10 烷基、环烷基、被至少一个直链或支链 1 -C 10 烷氧基烷基、氨基、苄基、四氢呋喃基、二氢呋喃基、呋喃基、吗啉基、哌啶基、四氢吡喃基、二氧戊环基、2,2-二甲基二氧戊环基、二氧杂环基、吡咯基、吡咯烷基、四氢恶唑基、二氢恶唑基、苯基或被 C 1 -C 10 烷基、C 1 -C 10 烷氧基，或卤代烃；W 是 其中每个 R 6 独立地为 H、直链或支链 C 1 -C 10 烷基，或直链或支链 C 1 -C 10 烷氧基烷基；以及 R 7 是烷基、环烷基、芳基或芳烷基；其中当 Z 是 -NH(C═O)-时，R 5 是直链或支链 C 1 -C 10 烷基、环烷基、被至少一个直链或支链 C 1 -C 10 烷基、环烷基、被至少一个直链或支链 1 -C 10 烷氧基烷基、氨基、苄基、四氢呋喃基、二氢呋喃基、呋喃基、吗啉基、哌啶基、四氢吡喃基、二氧戊环基、2,2-二甲基二氧戊环基、二氧杂环基、吡咯基、吡咯烷基、四氢恶唑基、二氢恶唑基、苯基或被 C 1 -C 10 烷基、C 1 -C 10 烷氧基，或卤代烃；W 是 其中每个 R 6 独立地为 H、直链或支链 C 1 -C 10 烷基，或直链或支链 C 1 -C 10 烷氧基烷基。此外，还公开了制备这些化合物的方法、包含这些化合物的药物组合物，以及通过施用这些药物组合物治疗患者的方法。
• US7678829B2
  申请人：——

  公开号：US7678829B2

  公开（公告）日：2010-03-16