1,2,3,4-四氢-1,3,6-三甲基-2-氧代-4-苯基-5-嘧啶羧酸 | 143335-38-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 1,2,3,4-四氢-1,3,6-三甲基-2-氧代-4-苯基-5-嘧啶羧酸
• 英文名称: 1,2,3,4-tetrahydro-1,3,6-trimethyl-2-oxo-4-phenyl-5-pyrimidinecarboxylic acid
• 英文别名: 1,3,6-trimethyl-2-oxo-4-phenyl-4H-pyrimidine-5-carboxylic acid
• CAS: 143335-38-0
• 化学式: C₁₄H₁₆N₂O₃
• 分子量: 260.293
• InChiKey: OPNHLILMXFDNLY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  60.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,2,3,4-四氢-1,3,6-三甲基-2-氧代-4-苯基-5-嘧啶羧酸 生成 (S)-1,3,6-Trimethyl-2-oxo-4-phenyl-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid
  参考文献：
  名称：

  Separation of enantiomers of 4-aryldihydropyrimidines by direct enantioselective HPLC. A critical comparison of chiral stationary phases

  摘要：

  The separation of the enantiomers of 29 racemic 4-aryldihydropyrimidine-5-carboxylates (DHPMs), aza-analogs of nifedipine-type dihydropyridine calcium channel modulators, was evaluated in direct enantioselective HPLC, employing the following commercially available chiral stationary phases (CSPs): Chiralcel OD-H, ChiraDex, Chirobiotic V and T, and Whelk-O1. In addition, a 1,2-diphenyl-1,2-diaminoethane based CSP and two quinine carbamate based chiral ion exchangers were also employed. For all 29 DHPMs separation of individual enantiomers could be achieved with at least one CSP with alpha-values ranging from 1.10 to 8.67. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0957-4166(97)00214-0
• 作为产物：
  描述：

  benzyl 1,6-dimethyl-4-phenyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate 在 palladium on activated charcoal 、 甲苯 氢气 、 sodium hydride 、 三乙胺 作用下， 以 甲醇 、 甲苯 、 paraffin 为溶剂， 25.0~60.0 ℃ 、300.0 kPa 条件下， 反应 2.0h， 生成 1,2,3,4-四氢-1,3,6-三甲基-2-氧代-4-苯基-5-嘧啶羧酸
  参考文献：
  名称：

  Synthesis and reactions of biginelli compounds −5. Facile preparation and resolution of a stable 5-dihydropyrimidinecarboxylic acid.

  摘要：

  The synthesis of enantiomerically pure 5-dihydropyrimidinecarboxylic acids 7a,b is described. Condensation of benzyl acetoacetate with methylurea and 2-naphthaldehyde gave Biginelli compound 3b, which after methylation and removal of the benzyl group led to racemic acid 5b. Fractional crystallization of diastereomeric alpha-methylbenzylammonium salts 6a,b followed by acidification provided the desired optically pure carboxylic acids 7a,b. Conversion of 7a,b to carboxylic acid azides 8a,b, followed by Curtius rearrangement and reaction with 10-undecenol led to chiral urethanes 10a,b. The absolute stereochemistry of acids 7a,b was established by X-ray analysis of diastereomeric alpha-methylbenzylammonium-carboxylate 6c.

  DOI：

  10.1016/s0040-4020(01)88301-0

文献信息

• Synthesis and reactions of Biginelli-compounds. Part 23. Chemoenzymatic syntheses of enanttiomerically pure 4-aryl-3,4-dihydropyrimidin-2(1H)-ones
  作者：Barbara Schnell、Wolfram Krenn、Kurt Faber、C. Oliver Kappe

  DOI：10.1039/b006372j

  日期：——

  Enantiomerically pure dihydropyrimidones (DHPMs) were prepared by lipase-catalyzed enzymatic resolution of two types of activated DHPM esters. In the first model series, pivaloyloxymethyl-activated DHPM C5-esters 10a–c were resolved on an analytical scale by various lipases in two different solvent systems with selectivities E < 50. Alternatively, attachment of an acetoxymethyl residue at the N3 position of the DHPM scaffold led to activated ester 15, which was selectively cleaved by Thermomyces lanuginosus lipase (E > 200) to furnish, after deprotection, DHPMs (R)- and (S)-13 on a semi-preparative scale. Treatment of (R)-13 with trichloroacetyl isocyanate produced the antihypertensive agent (R)-SQ 32926.

  通过脂肪酶催化的酶法拆分两种活化的二氢嘧啶酮酯，制备了对映体纯的二氢嘧啶酮（DHPM）。在第一个模型系列中，通过对不同脂肪酶在两种不同溶剂体系中的分析规模拆分，得到了选择性E < 50的茚满甲酰氧甲基活化的DHPM C5酯10a-c。或者，将乙酰氧甲基残基连接到DHPM骨架的N3位置，产生了活化的酯15，该酯被Thermomyces lanuginosus脂肪酶选择性裂解（E > 200），经脱保护后在中等制备规模上得到DHPM（R）-和（S）-13。处理（R）-13与三氯乙酰异氰酸酯，得到了降压剂（R）-SQ 32926。
• Separation of enantiomers of 4-aryldihydropyrimidines by direct enantioselective HPLC. A critical comparison of chiral stationary phases
  作者：Oliver P. Kleidernigg、C.Oliver Kappe

  DOI：10.1016/s0957-4166(97)00214-0

  日期：1997.6

  The separation of the enantiomers of 29 racemic 4-aryldihydropyrimidine-5-carboxylates (DHPMs), aza-analogs of nifedipine-type dihydropyridine calcium channel modulators, was evaluated in direct enantioselective HPLC, employing the following commercially available chiral stationary phases (CSPs): Chiralcel OD-H, ChiraDex, Chirobiotic V and T, and Whelk-O1. In addition, a 1,2-diphenyl-1,2-diaminoethane based CSP and two quinine carbamate based chiral ion exchangers were also employed. For all 29 DHPMs separation of individual enantiomers could be achieved with at least one CSP with alpha-values ranging from 1.10 to 8.67. (C) 1997 Elsevier Science Ltd.
• Synthesis and reactions of biginelli compounds −5. Facile preparation and resolution of a stable 5-dihydropyrimidinecarboxylic acid.
  作者：C.Oliver Kappe、Georg Uray、Peter Roschger、Wolfgang Lindner、Christoph Kratky、Walter Keller

  DOI：10.1016/s0040-4020(01)88301-0

  日期：1992.1

  The synthesis of enantiomerically pure 5-dihydropyrimidinecarboxylic acids 7a,b is described. Condensation of benzyl acetoacetate with methylurea and 2-naphthaldehyde gave Biginelli compound 3b, which after methylation and removal of the benzyl group led to racemic acid 5b. Fractional crystallization of diastereomeric alpha-methylbenzylammonium salts 6a,b followed by acidification provided the desired optically pure carboxylic acids 7a,b. Conversion of 7a,b to carboxylic acid azides 8a,b, followed by Curtius rearrangement and reaction with 10-undecenol led to chiral urethanes 10a,b. The absolute stereochemistry of acids 7a,b was established by X-ray analysis of diastereomeric alpha-methylbenzylammonium-carboxylate 6c.