1-cyclopentyl-7-ethoxy-3-ethyl-4,5-dihydro-1H-pyrazolo[3,4-c]pyridine | 303752-16-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 甲亚胺酸及其衍生物
• 英文名称: 1-cyclopentyl-7-ethoxy-3-ethyl-4,5-dihydro-1H-pyrazolo[3,4-c]pyridine
• 英文别名: 1H-Pyrazolo[3,4-C]pyridine, 1-cyclopentyl-7-ethoxy-3-ethyl-4,5-dihydro-；1-cyclopentyl-7-ethoxy-3-ethyl-4,5-dihydropyrazolo[3,4-c]pyridine
• CAS: 303752-16-1
• 化学式: C₁₅H₂₃N₃O
• 分子量: 261.367
• InChiKey: AUGGAAXFJUOEJJ-UHFFFAOYSA-N

物化性质

• 沸点：
  428.2±45.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  39.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-噻吩甲酰肼 、 1-cyclopentyl-7-ethoxy-3-ethyl-4,5-dihydro-1H-pyrazolo[3,4-c]pyridine 在 正丁醇 、 水 、 二氯甲烷 、 盐酸 、 异丙醇 作用下， 以 正丁醇 为溶剂， 反应 48.0h， 生成 9-环戊基-7-乙基-3-(2-噻吩基)-6,9-二氢-5H-吡唑并[3,4-c][1,2,4]三唑并[4,3-A]吡啶
  参考文献：
  名称：

  Process for preparing 8-cyclopentyl-6-ethyl-3-[substituted]-5,8-dihydro-4h-1,2,3a,7,8-pentaaza-as-indacenes and intermediates useful therein

  摘要：

  本发明涉及一种制备式（1.0.0）的8-环戊基-6-乙基-3-[取代]-5,8-二氢-4H-1,2,3a,7,8-五氮杂-异吲哚化合物及其药学上可接受的盐形式的方法，其中R1为氢；烷基；烷氧基；烷氧基烷基；烯基；环烷基，环烷基烷基；饱和或不饱和的杂环-(CH2)n-基团；或式（1.1.0）的基团：其中所有这些取代基在本说明书中详细定义；包括(a)将γ-己内酯和对甲氧基苯甲胺无溶剂反应混合物加热，从而产生一种被对甲氧基苯甲酰保护的酰胺化合物，式（2.0.0）：(b)还原式（2.0.0）的酰胺化合物，从而产生一种被对甲氧基苯甲酰保护的氨基醇化合物，式（3.0.0）：(c)用乙酰草酰氯酰化式（3.0.0）的氨基醇化合物，从而产生一种被对甲氧基苯甲酰保护的草酰胺乙酯化合物，式（4.0.0）：(d)氧化式（4.0.0）的草酰胺乙酯化合物，从而产生一种被对甲氧基苯甲酰保护的草酰胺酮化合物，式（5.0.0）：(e)环合式（5.0.0）的草酰胺酮化合物，从而产生一种被对甲氧基苯甲酰保护的吡啶酮化合物，式（6.0.0）：(f)用甲基对苯甲酸酯化式（6.0.0）的吡啶酮化合物，从而产生一种被对甲氧基苯甲酰保护的3-甲氧基吡啶酮化合物，式（7.0.0）：(g)用环戊基肼处理式（7.0.0）的3-甲氧基吡啶酮化合物，从而产生一种被对甲氧基苯甲酰保护的吡唑吡啶酮化合物，式（8.0.0）：(h)去除该吡唑吡啶酮化合物式（8.0.0）中的对甲氧基苯甲酰基团，从而产生一种内酰胺化合物，式（9.0.0）：(i)酯化式（9.0.0）的内酰胺化合物，从而产生一种相应的亚胺酯（亚胺）化合物，式（10.0.0）：(j)用式（11.0.0）的羧酸肼化合物处理式（10.0.0）的亚胺酯（亚胺）化合物，其中R1与上述含义相同，从而产生所述式（1.0.0）的8-环戊基-6-乙基-3-[取代]-5,8-二氢-4H-1,2,3a,7,8-五氮杂-异吲哚化合物。

  公开号：

  US20010039347A1
• 作为产物：
  描述：

  γ-己内酯 在 sodium hypochlorite 、 ammonium cerium (IV) nitrate 、 2,2,6,6-四甲基哌啶氧化物 、 水 、 sodium ethanolate 、 三乙酰氧基硼氢化钠 、 二异丁基氢化铝 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 21.66h， 生成 1-cyclopentyl-7-ethoxy-3-ethyl-4,5-dihydro-1H-pyrazolo[3,4-c]pyridine
  参考文献：
  名称：

  Process Research and Large-Scale Synthesis of a Novel 5,6-Dihydro-(9H)-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-a]pyridine PDE-IV Inhibitor

  摘要：

  An efficient synthesis of the PDE IV inhibitor, 9H.-cyclopentyl.. 7-ethyl-3-(thiophen-2-yl)-pyrazolo[3,4-c]-1,2,4-triazolo-,5,6-dihydro-[4,3-a]pyridine I is described. Starting from commercially available gamma -caprolactone, the synthesis was carried out in 10 steps. Key transformations were the selective O-methylation of diketone, 3-hydroxy-1-(4-methoxybenzyl)-4-propionyl-5,6-dihydro-1H-pyridin-2-one, with dimethyl sulfate and cesium carbonate in dimethylformamide, a one-pot pyrazole formation with subsequent acidic deprotection to provide lactam, 1-cyclopentyl-3-ethyl-1,4,5,6-tetrahydropyrazolo[3,4,c]pyridin-7- one, and finally the utilization of imidate, 1-cyclopentyl-7-ethoxy-3-ethyl-4,5-dihydro-1H-pyrazolo[3,4-c]pyridine for the introduction of the triazole moiety. This process avoided the use of harsh reaction conditions, undesirable reagents and overcame the environmental concerns in the original synthesis.

  DOI：

  10.1021/op010222x

文献信息

• Process for preparing 8-cyclopentyl-6-ethyl-3-[substituted]-5,8-dihydro-4h-1,2,3a,7,8-pentaaza-as-indacenes and intermediates useful therein
  申请人：——

  公开号：US20010039347A1

  公开（公告）日：2001-11-08

  The invention concerns a method of preparing an 8-cyclopentyl-6-ethyl-3-[substituted]-5,8-dihydro-4H-1,2,3a,7,8-pentaaza-as-indacene compound of Formula (1.0.0): 1 and pharmaceutically acceptable salt forms thereof, where R 1 is hydrogen; alkyl; alkoxy; alkoxyalkyl; alkenyl; cycloalkyl, cycloalkylalkyl; a saturated or unsaturated heterocyclic-(CH 2 ) n — group; or a group of Formula (1.1.0): 2 wherein all of said substituents are defined in more detail in the instant specification; comprising (a) subjecting a solventless reaction mixture of &ggr;-caprolactone and p-methoxybenzylamine to heating whereby there is produced an amide compound N-protected by p-methoxybenzyl, of Formula (2.0.0): 3 (b) reducing said amide compound of Formula (2.0.0) whereby there is produced an amino alcohol compound N-protected by p-methoxybenzyl, of Formula (3.0.0): 4 (c) acylating said aminoalcohol compound of Formula (3.0.0) with ethyl oxalyl chloride whereby there is produced an oxalamic acid ethyl ester compound N-protected by p-methoxybenzyl, of Formula (4.0.0): 5 (f) oxidizing said oxalamic acid ethyl ester compound of Formula (4.0.0) whereby there is produced an oxalamide ketone compound N-protected by p-methoxybenzyl, of Formula (5.0.0): 6 (e) ring closing said oxalamide ketone compound of Formula (5.0.0) whereby there is produced a pyridinone compound N-protected by p-methoxybenzyl, of Formula (6.0.0): 7 (f) O-methylating said pyridinone compound of Formula (6.0.0) whereby there is produced a 3-methoxy-pyridinone compound N-protected by p-methoxybenzyl, of Formula (7.0.0): 8 (g) treating said 3-methoxy-pyridinone compound of Formula (7.0.0) with cyclopentylhydrazine, whereby there is produced a pyrazolopyridinone compound N-protected by p-methoxybenzyl, of Formula (8.0.0) 9 (h) deprotecting said pyrazolopyridinone compound of Formula (8.0.0) by removing said p-methoxybenzyl group therefrom, whereby there is produced a lactam compound of Formula (9.0.0): 10 (i) esterifying said lactam compound of Formula (9.0.0) whereby there is produced a corresponding imino ester (imidate) compound of Formula (10.0.0): 11 (j) treating said imino ester (imidate) compound of Formula (10.0.0) with a carboxylic hydrazide compound of Formula (11.0.0): 12 where R 1 has the same meaning as set out further above; whereby there is produced said 8-cyclopentyl-6-ethyl-3-[substituted]-5,8-dihydro-4H-1,2,3a,7,8-pentaaza-as-indacene compound of Formula (1.0.0).

  本发明涉及一种制备8-环戊基-6-乙基-3-[取代]-5,8-二氢-4H-1,2,3a,7,8-五氮杂-茚化合物及其药学可接受的盐形式的方法，其中R1为氢；烷基；烷氧基；烷氧基烷基；烯基；环烷基，环烷基烷基；饱和或不饱和的杂环-(CH2)n-基；或式(1.1.0)的基团：其中所有的取代基在本说明书中有更详细的定义；包括(a)将&ggr;-己内酯和对甲氧基苯甲胺无溶剂反应混合物加热，从而生成一种由对甲氧基苯甲基保护的酰胺化合物，式(2.0.0)：(b) 还原式(2.0.0)的酰胺化合物，从而生成一种由对甲氧基苯甲基保护的氨基醇化合物，式(3.0.0)：(c) 用乙酰乙酸乙酯酰化式(3.0.0)的氨基醇化合物，从而生成一种由对甲氧基苯甲基保护的草酸乙酯化合物，式(4.0.0)：(d) 氧化式(4.0.0)的草酸乙酯化合物，从而生成一种由对甲氧基苯甲基保护的草酰胺酮化合物，式(5.0.0)：(e) 环合式(5.0.0)的草酰胺酮化合物，从而生成一种由对甲氧基苯甲基保护的吡啶酮化合物，式(6.0.0)：(f) 用O-甲基化式(6.0.0)的吡啶酮化合物，从而生成一种由对甲氧基苯甲基保护的3-甲氧基吡啶酮化合物，式(7.0.0)：(g) 用环戊基肼处理式(7.0.0)的3-甲氧基吡啶酮化合物，从而生成一种由对甲氧基苯甲基保护的吡唑吡啶酮化合物，式(8.0.0)：(h) 去除式(8.0.0)的p-甲氧基苯甲基保护基团，从而得到一种内酰胺化合物，式(9.0.0)：(i) 酯化式(9.0.0)的内酰胺化合物，从而生成一种相应的亚胺酯(亚胺)化合物，式(10.0.0)：(j) 用式(11.0.0)的羧酸肼化合物处理式(10.0.0)的亚胺酯(亚胺)化合物，其中R1的含义与上述相同；从而得到所述的8-环戊基-6-乙基-3-[取代]-5,8-二氢-4H-1,2,3a,7,8-五氮杂-茚化合物，式(1.0.0)。
• Process for preparing 8-cyclopentyl-6-ethyl-3-[substituted]-5,8-dihydro-4H-1,2,3a,7,8-pentaaza-as-indacenes and intermediates useful therein
  申请人：Pfizer Inc.

  公开号：US06326495B2

  公开（公告）日：2001-12-04

  The invention concerns a method of preparing an 8-cyclopentyl-6-ethyl-3-[substituted]-5,8-dihydro-4H-1,2,3a,7,8-pentaaza-as-indacene compound of the formula: and pharmaceutically acceptable salt forms thereof, where R1 is hydrogen; alkyl; alkoxy; alkoxyalkyl; alkenyl; cycloalkyl; cycloalkylalkyl; a saturated or unsaturated heterocyclic-(CH2)n—group; or a group of the formula —(Y)b—(Z)c-phenyl-(R5)a; comprising: (a) subjecting a solventless reaction mixture of &ggr;-caprolactone and p-methoxybenzylamine to heating whereby there is produced an amide compound N-protected by p-methoxybenzyl; (b) reducing said amide compound whereby there is produced an amino alcohol compound N-protected by p-methoxybenzyl; (c) acylating said aminoalcohol compound with ethyl oxalyl chloride whereby there is produced an oxalamic acid ethyl ester compound N-protected by p-methoxybenzyl; (d) oxidizing said oxalamic acid ethyl ester compound whereby there is produced an oxalamide ketone compound N-protected by p-methoxybenzyl, of the formula: (e) ring closing said oxalamide ketone compound whereby there is produced a pyridinone compound N-protected by p-methoxybenzyl, of the formula: (f) O-methylating said pyridinone compound whereby there is produced a 3-methoxy-pyridinone compound N-protected by p-methoxybenzyl; (g) treating said 3-methoxy-pyridinone compound with cyclopentylhydrazine, whereby there is produced a pyrazolopyridinone compound N-protected by p-methoxybenzyl; (h) deprotecting said pyrazolopyridinone compound by removing said p-methoxybenzyl group therefrom, whereby there is produced a lactam compound of the formula: (i) esterifying said lactam compound whereby there is produced a corresponding imino ester (imidate) compound of the formula: and (j) treating said imino ester (imidate) compound with a carboxylic hydrazide compound of the formula: R1—C(═O)—NH—NH2, where R1 has the same meaning as set out further above; whereby there is produced said 8-cyclopentyl-6-ethyl-3-[substituted]-5,8-dihydro-4H-1,2,3a,7,8-pentaaza-as-indacene.

  本发明涉及一种制备8-环戊基-6-乙基-3-［取代］-5,8-二氢-4H-1,2,3a,7,8-五氮杂萘化合物及其药学上可接受的盐形式的方法，其中R1为氢; 烷基; 烷氧基; 烷氧基烷基; 烯基; 环烷基; 环烷基烷基; 饱和或不饱和的杂环-(CH2)n-基团; 或式为-(Y)b-(Z)c-苯基-(R5)a的基团; 包括：(a)将&ggr;-己内酯和对甲氧基苯甲胺的无溶剂反应混合物加热，从而产生一种受对甲氧基苯甲基保护的酰胺化合物; (b)还原所述酰胺化合物，从而产生一种受对甲氧基苯甲基保护的氨基醇化合物; (c)用草酰氯乙酯酰化所述氨基醇化合物，从而产生一种受对甲氧基苯甲基保护的草酰胺乙酯化合物; (d)氧化所述草酰胺乙酯化合物，从而产生一种受对甲氧基苯甲基保护的草酰胺酮化合物，其式为：(e)环合所述草酰胺酮化合物，从而产生一种受对甲氧基苯甲基保护的吡啶酮化合物，其式为：(f)用甲基碘化物甲基化所述吡啶酮化合物，从而产生一种受对甲氧基苯甲基保护的3-甲氧基吡啶酮化合物; (g)用环戊基肼处理所述3-甲氧基吡啶酮化合物，从而产生一种受对甲氧基苯甲基保护的吡唑吡啶酮化合物; (h)去除所述吡唑吡啶酮化合物中的p-甲氧基苯甲基团，从而去保护，产生一种内酰胺化合物，其式为：(i)酯化所述内酰胺化合物，从而产生一种相应的亚胺酯(亚胺)化合物，其式为：(j)用式为R1-C(═O)-NH-NH2的羧酸肼化合物处理所述亚胺酯(亚胺)化合物，其中R1具有上述相同的含义; 从而产生所述8-环戊基-6-乙基-3-［取代］-5,8-二氢-4H-1,2,3a,7,8-五氮杂萘化合物。
• Pyrazolopyridinone
  申请人：Pfizer Products Inc.

  公开号：EP1380585A1

  公开（公告）日：2004-01-14

  The invention concerns a compound comprising a member selected from the group consisting of the tosylate and besylate salts of a pyrazolopyridinone compound N-protected by p-methoxybenzyl, of Formulas (8.1.0) and (8.1.1), respectively, as follows:

  本发明涉及一种化合物，其成员选自分别为式(8.1.0)和式(8.1.1)的吡唑并吡啶酮化合物的对甲氧基苄基保护的对甲氧基苄基甲苯磺酸盐和对甲氧基苄基苯磺酸盐所组成的组：
• Process for preparing 8-cyclopentyl-6-ethyl-3-(substituted)-5,8-dihydro-4H-1,2,3A,7,8-pentaaza-as-indacenes and intermediates useful therein
  申请人：Pfizer Products Inc.

  公开号：EP1048667B1

  公开（公告）日：2003-10-22
• US6326495B2
  申请人：——

  公开号：US6326495B2

  公开（公告）日：2001-12-04