N-(5-((4-乙基哌嗪-1-基)甲基)吡啶-2-基)-5-氟-4-(4-氟-1-异丙基-2-甲基-1H-苯并[d]咪唑-6-基)嘧啶-2-胺

CAS号：1231929-97-7

CAS号1231929-97-7, 是Cell Cycle类化合物, 分子量为506.59, 分子式C27H32F2N8, 标准纯度99%, 毕得医药(Bidepharm)提供1231929-97-7批次质检（如NMR, HPLC, GC）等检测报告。

N-(5-((4-乙基哌嗪-1-基)甲基)吡啶-2-基)-5-氟-4-(4-氟-1-异丙基-2-甲基-1H-苯并[d]咪唑-6-基)嘧啶-2-胺 (请以英文为准,中文仅做参考)

N-(5-((4-Ethylpiperazin-1-yl)methyl)pyridin-2-yl)-5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-amine , Abemaciclib

货号：BD304642 N-(5-((4-Ethylpiperazin-1-yl)methyl)pyridin-2-yl)-5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-amine 标准纯度：, 99%

标准纯度	包装	价格	上海	深圳	天津	武汉	成都	VIP价格	数量

检测信息
批次：
纯度：批次查询可见
COA MS HPLC LC-MS Microanalysis

产品名称 :	N-(5-((4-Ethylpiperazin-1-yl)methyl)pyridin-2-yl)-5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-amine , Abemaciclib
中文名称 :	N-(5-((4-乙基哌嗪-1-基)甲基)吡啶-2-基)-5-氟-4-(4-氟-1-异丙基-2-甲基-1H-苯并[d]咪唑-6-基)嘧啶-2-胺(请以英文为准,中文仅做参考)
CAS号 :	1231929-97-7
分子式 :	C₂₇H₃₂F₂N₈
线性分子式 :	-
分子量 :	506.59
MDL NO :	MFCD22665744
沸点 :	-
Pubchem ID :	46220502
InChIKey :	UZWDCWONPYILKI-UHFFFAOYSA-N

常用 :

SDS-BD304642

2D :

3D :

【用途一】

计算化学

Physicochemical Properties

Num. heavy atoms	37
Num. arom. heavy atoms	21
Fraction Csp3	0.41
Num. rotatable bonds	7
Num. H-bond acceptors	8.0
Num. H-bond donors	1.0
Molar Refractivity	149.17
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	75.0 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	4.16
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	3.84
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	4.86
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	2.63
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	4.28
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	3.96

Water Solubility

Log S (ESOL)? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-5.36
Solubility	0.00222 mg/ml ; 0.00000438 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Moderately soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-5.11
Solubility	0.00392 mg/ml ; 0.00000775 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Moderately soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-8.62
Solubility	0.00000123 mg/ml ; 0.0000000024 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Poorly soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	No
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	Yes
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	No
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	Yes
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	Yes
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	Yes
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	Yes
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-6.66 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	1.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	0.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	0.0 alert
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	2.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	3.87

合成路线：*资料仅供科研用途参考，更多细节请参阅原文出处。

1~19 ►

1. 合成：1231929-97-7

5308-25-8

N/A

1231929-97-7

产率

合成条件

实验步骤

74%

With formic acid; trimethyl orthoformate In acetonitrile at 80℃; for 16 h; Sealed tube

向装有搅拌棒的20mL反应物中加入醛7（500mg，1.22mmol，1.0当量），N-乙基哌嗪（0.31mL，2.45mmol，2.0当量），ACN（5mL），原甲酸三甲酯（0.27mL），2.45mmol，2.0当量），和甲酸（0.187mL，4.9mmol，4.0当量）。密封反应容器，将搅拌的混合物加热至80℃，保持16小时。将所得浆液冷却至环境温度，过滤收集固体。然后将湿饼用ACN（5mL）洗涤，然后在真空烘箱中在45℃下干燥16小时，得到abemaciclib 1（456mg，0.90mmol，74％收率），为灰白色固体。化合物1：IR（膜）mmax = 3232,3167,3089,3030,2970,2936,2810,1584,1533,1477,1434,1398,1291cm -1; 1H NMR（400MHz，CDCl3）：d = 9.05（s，1H），8.47（d，J = 6.0Hz，1H），8.38（d，J = 12.0Hz，1H），8.30（d，J = 3.0Hz），1H），8.16（d，J = 1.5 Hz，1H），7.75（dd，J = 12.0,1.5 Hz，1H），7.66（dd，J = 12.0,3.0 Hz，1H），4.70（septet，J = 6.0 Hz，1H），3.47（s，2H），2.65（s，3H），2.48（br m，8H），2.39（q，J = 12.0 Hz，2H），1.68（d，J = 6.0 Hz，6H ），1.05（t，J = 12.0 Hz，3H）ppm; 13CNMR（100MHz，CDCl3）：d = 155.5,153.7,153.5,152.4,151.5,151.1,148.9,147.4,139.2,136.6,134.2,127.7,127.3,111.6,108.9,108.3,60.0,53.1,52.9,52.5， 48.8,21.6,15.2,12.2ppm; HR-MS [ESI]：C 27 H 32 F 2 N 8 H + [M + H +]的计算值：507.2791，实测值507.2789。

参考文献：

[1] Tetrahedron Letters, 2015, vol. 56, # 7, p. 949 - 951

2. 合成：1231929-97-7

N/A

1231929-97-7

产率

合成条件

实验步骤

73.1%

With sodium hydroxide In butan-1-ol at 90 - 100℃; Inert atmosphere

10057]加入N- [5-（4-乙基 - 哌嗪-1-基 - 甲基）吡啶-2-基]硝酸胍（IX）（3.6g，11mmol），6-（3-N，N-二甲基铵） -2-氟-2-丙烯酰酮-1-基）-4-氟-1-异丙基-2-甲基-1H-苯并咪唑（II）（3.1g，10mmol），氢氧化钠（0.6g，15mmol）向反应烧瓶中加入25mL正丁醇和溶剂，在氮气氛下，缓慢升温至90-100℃，搅拌12-16小时。并用TLC检测反应的结束。使自然冷却至室温，并将有固体沉淀。用乙醇和水（1：2，V / V）重结晶，真空干燥，得到灰白色固体，l3emaciclib（I）3.7g，收率为73.1％; 1 H NMR（DMSO-d5）1.16（t，3H），1.62（m，6H），2.51（q，2H），2.64（s，3H），2.68-2.73（m，4H），2.83-3.04（m ，4H），3.52（s，2H），4.65（m，1H），7.12-7.21（m，2H），7.45-7.64（m，2H），8.21-8.27（m，2H），9.07（s，1H））; 质谱（E1）：m / z 507（M + H）。

参考文献：

[1] Patent: US2017/305884, 2017, A1. Location in patent: Paragraph 0057

3. 合成：1231929-97-7

1180132-17-5

1231930-42-9

1231929-97-7

产率

合成条件

实验步骤

57.3%

With potassium carbonate; [5-(diphenylphosphanyl)-9,9-dimethyl-9H-xanthen-4-yl]diphenylphosphane; bis(dibenzylideneacetone)-palladium⁽⁰⁾ In tert-Amyl alcohol at 100℃; for 19 h;

类似于WO2010 / 075074的实施例33，通过6-（2-氯-5-氟 - 嘧啶-4-基）-4-氟-1-异丙基-2-甲基的混合物将氮气鼓泡5分钟-1H-苯并咪唑（5g; 15.5mmol），5-（4-乙基 - 哌嗪-1-基甲基） - 吡啶-2-基胺（3.48g; 15.8mmol），K 2 CO 3（4.71g; 34.1mmol）和黄原酸（179mg; 0.3mmol）在叔戊醇（25mL）中的溶液。加入三（二亚苄基 - 丙酮）二钯（O）（142mg; 0.2mmol），将浆液加热至100℃。当HPLC表明嘧啶基苯并咪唑完全转化时，将浆液搅拌19小时。将混合物冷却至室温并用二氯甲烷稀释。将浆液在Whatman玻璃纤维过滤器上过滤，并将获得的滤液用HCl水溶液（4N; 2×25mL）萃取。将收集的含水萃取物与活性炭（250mg）一起搅拌，过滤（Whatman）并用NaOH水溶液（17％; 30mL）碱化。将所得混合物用DCM（2×20）萃取，经Na 2 SO 4干燥，过滤，在Quadrasil（800mg）上搅拌，过滤并在减压下浓缩。将剩余的粗黄色固体在丙酮中浆化，过滤，用丙酮洗涤并在减压下干燥以分离细黄色粉末。产量：4.5g（57.3％）化学纯度：99.4％（λ= 320nm处的峰面积）。

22.11 g

With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; caesium carbonate; [5-(diphenylphosphanyl)-9,9-dimethyl-9H-xanthen-4-yl]diphenylphosphane In 1,4-dioxane at 110℃; for 2 h; Inert atmosphere

将氮气鼓泡成6-（2-氯-5-氟 - 嘧啶-4-基）-4-氟-1-异丙基-2-甲基-1H-苯并咪唑（15.9g），5-（4-乙基）的混合物 - 哌嗪-1-基甲基） - 吡啶-2-基胺（10.85g），碳酸铯（32.10g），三（二亚苄基丙酮）二钯（1.82g），4,5-双（二苯基膦基）-9,9-二甲基x吨（ 2.35g）在1,4-二恶烷（197.06mL）中的溶液。将混合物在110℃的预热油浴中加热2小时。冷却至室温，用二氯甲烷稀释并用CELITE垫过滤。真空除去溶剂，用硅胶柱色谱法纯化，用二氯甲烷/甲醇（2）洗脱，然后用二氯甲烷/甲醇-NH 2 2M 2洗脱，得到22.11g标题化合物。 MS（ES +）：m / z = 507（M + H）+。

参考文献：

[1] Patent: WO2017/108781, 2017, A1. Location in patent: Page/Page column 13; 14
[2] Patent: US2010/160340, 2010, A1. Location in patent: Page/Page column 14
[3] Patent: WO2015/130540, 2015, A1. Location in patent: Page/Page column 23

骨架产品推荐

历史浏览记录

摩尔计算器

浓度
x
体积
x
分子量
=
质量

浓度 x 体积 x 分子量 = 质量

合成路线

1. 合成：1231929-97-7

5308-25-8

N/A

1231929-97-7

产率

合成条件

实验参考步骤

74%

With formic acid; trimethyl orthoformate In acetonitrile at 80℃; for 16 h; Sealed tube

参考文献：

[1] Tetrahedron Letters, 2015, vol. 56, # 7, p. 949 - 951

2. 合成：1231929-97-7

N/A

1231929-97-7

产率

合成条件

实验参考步骤

73.1%

With sodium hydroxide In butan-1-ol at 90 - 100℃; Inert atmosphere

参考文献：

[1] Patent: US2017/305884, 2017, A1. Location in patent: Paragraph 0057

3. 合成：1231929-97-7

1180132-17-5

1231930-42-9

1231929-97-7

产率

合成条件

实验参考步骤

57.3%

With potassium carbonate; [5-(diphenylphosphanyl)-9,9-dimethyl-9H-xanthen-4-yl]diphenylphosphane; bis(dibenzylideneacetone)-palladium⁽⁰⁾ In tert-Amyl alcohol at 100℃; for 19 h;

22.11 g

With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; caesium carbonate; [5-(diphenylphosphanyl)-9,9-dimethyl-9H-xanthen-4-yl]diphenylphosphane In 1,4-dioxane at 110℃; for 2 h; Inert atmosphere

参考文献：

4. 合成：1231929-97-7

1231930-37-2

1231929-97-7

参考文献：

[1] Tetrahedron Letters, 2015, vol. 56, # 7, p. 949 - 951
[2] Patent: WO2015/130540, 2015, A1

5. 合成：1231929-97-7

N/A

1231929-97-7

参考文献：

[1] Patent: US2017/305884, 2017, A1
[2] Patent: US2017/305884, 2017, A1

6. 合成：1231929-97-7

5509-65-9

1231929-97-7

参考文献：

[1] Patent: US2017/305884, 2017, A1
[2] Patent: US2017/305884, 2017, A1

7. 合成：1231929-97-7

811799-69-6

1231929-97-7

参考文献：

[1] Patent: US2017/305884, 2017, A1
[2] Patent: US2017/305884, 2017, A1

8. 合成：1231929-97-7