4-[6-[(6-溴-8-环戊基-7,8-二氢-5-甲基-7-氧代吡啶并[2,3-d]嘧啶-2-基)氨基]-3-吡啶基]-1-哌嗪羧酸叔丁酯 | 571188-82-4

物质功能分类

分析化学 - 标准品 - 药典标准品和杂质标准品

分子结构分类

有机化合物 - 有机杂环化合物 - 二嗪烷类

中文名称

4-[6-[(6-溴-8-环戊基-7,8-二氢-5-甲基-7-氧代吡啶并[2,3-d]嘧啶-2-基)氨基]-3-吡啶基]-1-哌嗪羧酸叔丁酯

中文别名

帕布昔利布中间体1；4-[6-[(6-溴-8-环戊基-7,8-二氢-5-甲基-7-氧代吡啶并[2,3-D]嘧啶-2-基)氨基]-3-吡啶基]-1-哌嗪羧酸叔丁酯

英文名称

4-[6-(6-bromo-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-ylamino)pyridin-3-yl]piperazine-1-carboxylic acid tert-butyl ester

英文别名

tert-butyl 4-(6-((6-bromo-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazine-1-carboxylate；4-[6-(6-bromo-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro-Pyrido[2,3-d]pyrimidin-2-ylamino)-Pyridin-3-yl]-piperazin-1-carboxylic acid tert-butyl ester；tert‑butyl 4‑(6‑((6‑bromo‑8‑cyclopentyl‑5‑methyl‑7‑oxo‑7,8‑dihydropyrido[2,3‑d]pyrimidin‑2‑yl)amino)pyridin‑3‑yl)piperazine‑1‑carboxylate；tert-butyl 4-[6-[(6-bromo-8-cyclopentyl-5-methyl-7-oxopyrido[2,3-d]pyrimidin-2-yl)amino]pyridin-3-yl]piperazine-1-carboxylate

4-[6-[(6-溴-8-环戊基-7,8-二氢-5-甲基-7-氧代吡啶并[2,3-d]嘧啶-2-基)氨基]-3-吡啶基]-1-哌嗪羧酸叔丁酯化学式

CAS

571188-82-4

化学式

C₂₇H₃₄BrN₇O₃

mdl

——

分子量

584.516

InChiKey

UTSOLZWQDXJQRH-UHFFFAOYSA-N

BEILSTEIN

——

EINECS

——

物化性质

熔点：

>250℃
沸点：

720.0±70.0 °C(Predicted)
密度：

1.439±0.06 g/cm3(Predicted)

计算性质

辛醇/水分配系数(LogP)：

4.1
重原子数：

38
可旋转键数：

6
环数：

5.0
sp3杂化的碳原子比例：

0.52
拓扑面积：

104
氢给体数：

1
氢受体数：

8

安全信息

危险性防范说明：

P261,P305+P351+P338
危险性描述：

H302,H315,H319,H335
储存条件：

2~8℃

SDS

SDS：8aa23abf4b743418c84d184c830cbaaa

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制备方法与用途

帕布昔利布杂质23是帕布昔利的杂质，由辉瑞公司开发，用于治疗乳腺癌。它是一种选择性细胞周期素依赖性激酶（CDK4 和 CDK6）抑制剂。该化合物源自 6-溴-2-氯-8-环戊基-5-甲基吡啶-[2,3-d]嘧啶-7（8H）-酮，并用于制备吡啶基[2,3-d]嘧啶-7（8H）-酮衍生物，作为 CDK4 和/或 CDK6 抑制剂以治疗相关疾病。

上下游信息

上游原料

中文名称	英文名称	CAS号	化学式	分子量
6-溴-8-环戊基-5-甲基-2-甲硫基-8H-吡啶并[2,3-d]嘧啶-7-酮	6-bromo-8-cyclopentyl-5-methyl-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one	362656-25-5	C₁₄H₁₆BrN₃OS	354.271
Palbociclib中间体	6-bromo-8-cyclopentyl-5-methyl-2-(methylsulfinyl)pyrido[2,3-d]pyrimidin-7(8H)-one	571188-81-3	C₁₄H₁₆BrN₃O₂S	370.27
6-溴-2-氯-8-环戊基-5-甲基-吡啶并[2,3-D]嘧啶-7(8H)-酮	6-bromo-2-chloro-8-cyclopentyl-5-methylpyrido[2,3-d]pyrimidin-7(8H)-one	1016636-76-2	C₁₃H₁₃BrClN₃O	342.623
8-环戊基-5-甲基-2-甲基磺酰基-8H-吡啶并[2,3-d]嘧啶-7-酮	8-cyclopentyl-5-methyl-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one	362656-23-3	C₁₄H₁₇N₃OS	275.374
2-氯-8-环戊基-5-甲基-8H-吡啶并[2,3-D]嘧啶-7-酮	2-chloro-8-cyclopentyl-5-methyl-8H-pyrido[2,3-d]pyrimidin-7-one	1013916-37-4	C₁₃H₁₄ClN₃O	263.727

下游产品

中文名称	英文名称	CAS号	化学式	分子量
PALBOCICLIB杂质A	6-bromo-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidine-7(8H)-one	851067-56-6	C₂₂H₂₆BrN₇O	484.399
——	tert-butyl 4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazine-1-carboxylate	1651214-74-2	C₂₉H₃₇N₇O₄	547.657
4-[6-[[8-环戊基-6-(1-乙氧基乙烯基)-5-甲基-7-氧代-7,8-二氢吡啶并[2,3-d]嘧啶-2-基]氨基]吡啶-3-基]哌嗪-1-羧酸叔丁酯	4-{6-[8-cyclopentyl-6-(1-ethoxyvinyl)-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-ylamino]pyridin-3-yl}piperazine-1-carboxylic acid tert-butyl ester	571189-10-1	C₃₁H₄₁N₇O₄	575.711
——	tert-butyl 4-(6-((8-cyclopentyl-5-methyl-7-oxo-6-(1-propoxyvinyl)-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)-piperazin-1-carboxylate	——	C₃₂H₄₃N₇O₄	589.738
——	tert-butyl 4-(6-((6-(1-butoxyvinyl)-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazine-1-carboxylate	——	C₃₃H₄₅N₇O₄	603.765
帕布昔利布	PD 0332991	571190-30-2	C₂₄H₂₉N₇O₂	447.54
——	2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-1-yl)-N-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethoxy)ethyl)acetamide	——	C₄₃H₄₉N₁₁O₈	847.931
——	2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-1-yl)-N-(2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethoxy)ethoxy)ethyl)acetamide	——	C₄₅H₅₃N₁₁O₉	891.984
——	2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-1-yl)-N-(2-(2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethoxy)ethoxy)ethoxy)ethyl)acetamide	——	C₄₇H₅₇N₁₁O₁₀	936.037
——	2-(4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-1-yl)-N-(14-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)-3,6,9,12-tetraoxatetradecyl)acetamide	——	C₄₉H₆₁N₁₁O₁₁	980.09
——	4-(6-(4-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-1-yl)methyl)-1H-1,2,3-triazol-1-yl)hex-1-yn-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione	——	C₄₆H₄₈N₁₂O₆	864.964
——	4-(7-(4-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-1-yl)methyl)-1H-1,2,3-triazol-1-yl)hept-1-yn-1-yl)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione	——	C₄₇H₅₀N₁₂O₆	878.991
——	4-((2-(2-(4-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-1-yl)methyl)-1H-1,2,3-triazol-1-yl)ethoxy)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione	2366268-80-4	C₄₄H₄₉N₁₃O₇	871.956
——	4-((2-(2-(2-(2-(4-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-1-yl)methyl)-1H-1,2,3-triazol-1-yl)ethoxy)ethoxy)ethoxy)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione	——	C₄₈H₅₇N₁₃O₉	960.062
——	4-((14-(4-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-1-yl)methyl)-1H-1,2,3-triazol-1-yl)-3,6,9,12-tetraoxatetradecyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione	——	C₅₀H₆₁N₁₃O₁₀	1004.12
——	4-((2-(2-(2-(4-((4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazin-1-yl)methyl)-1H-1,2,3-triazol-1-yl)ethoxy)ethoxy)ethyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione	——	C₄₆H₅₃N₁₃O₈	916.009

反应信息

作为反应物：

描述：

4-[6-[(6-溴-8-环戊基-7,8-二氢-5-甲基-7-氧代吡啶并[2,3-d]嘧啶-2-基)氨基]-3-吡啶基]-1-哌嗪羧酸叔丁酯在盐酸、 palladium diacetate 、 N,N-二异丙基乙胺、双(2-二苯基磷苯基)醚作用下，以乙醇、水为溶剂，反应 30.0h，生成帕布昔利布

参考文献：

名称：

靶向靶向嵌合体降解蛋白的CDK6的潜在和优先降解。

摘要：

开发了劫持癌症治疗靶标CDK6的重点PROTAC文库。为理解这些PROTAC中的降解曲线差异，提出了一种设计原则，即“匹配/不匹配”。值得注意的是，通过将CDK6抑制剂palbociclib和E3连接酶CRBN募集者pomalidomide连接起来，可产生具有特定且显着的CDK6降解潜能的强效PROTAC。PROTAC强烈抑制包括多发性骨髓瘤在内的造血癌细胞的增殖，并强烈抑制CDK6的拷贝扩增/突变形式的降解，这表明了其未来的潜在临床应用。

DOI：