CAS号：54-85-3

CAS号54-85-3, 是Anti-infection类化合物, 分子量为137.14, 分子式C6H7N3O, 标准纯度98+%, 毕得医药(Bidepharm)提供54-85-3批次质检（如NMR, HPLC, GC）等检测报告。

吡啶-4-酰肼 (请以英文为准,中文仅做参考)

4-Pyridinecarboxylic acid hydrazide , Isoniazid

货号：BD21389 4-Pyridinecarboxylic acid hydrazide 标准纯度：, 98+%

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 :	4-Pyridinecarboxylic acid hydrazide , Isoniazid
中文名称 :	吡啶-4-酰肼(请以英文为准,中文仅做参考)
CAS号 :	54-85-3
分子式 :	C₆H₇N₃O
线性分子式 :	H₂NNHCOC₅H₄N
分子量 :	137.14
MDL NO :	MFCD00006426
沸点 :	-
Pubchem ID :	3767
InChIKey :	QRXWMOHMRWLFEY-UHFFFAOYSA-N

常用 :

SDS-BD21389

2D :

JSON XML ASN SDF

3D :

JSON XML ASN SDF

【用途一】

计算化学

Physicochemical Properties

Num. heavy atoms	10
Num. arom. heavy atoms	6
Fraction Csp3	0.0
Num. rotatable bonds	2
Num. H-bond acceptors	3.0
Num. H-bond donors	2.0
Molar Refractivity	35.13
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	68.01 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	0.03
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	-0.7
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	-0.31
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.	-0.47
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	-0.27
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	-0.35

Water Solubility

Log S (ESOL)? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-0.56
Solubility	37.7 mg/ml ; 0.275 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-0.25
Solubility	76.6 mg/ml ; 0.558 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very 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	-1.64
Solubility	3.17 mg/ml ; 0.0231 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	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	No
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	No
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	No
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	No
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	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-7.63 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	0.0
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	1.0
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	2.0 alert
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	1.0
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)	1.24

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。

1~26 ►

1. 合成：54-85-3

1570-45-2

54-85-3

产率

合成条件

实验步骤

86%

With hydrazine hydrate In ethanol at 60℃; for 1 h;

将市售的异烟酸异丙酯与水合肼回流。在60℃下保持1小时，蒸发溶剂。用乙醚研磨该固体，得到纯的酰肼2，产率86％。用CS2和KOH在60℃下处理酰肼2 18小时，在真空浓缩后产生固体。发现该物质可以通过用H 2 O研磨然后过滤而容易地纯化，得到硫醇3，产率为78％，因此避免了前两步的色谱法。这种操作简单的程序为子序列聚焦的文库合成提供了多克量的3。最后，通过使用K 2 CO 3作为碱，在室温DMF中通过硫醇3与取代的芳基溴化物的亲核置换反应实现芳环的多样化。

86%

With hydrazine hydrate In ethanol at 60℃; for 1 h;

将市售的异烟酸异丙酯与水合肼在60℃下回流1小时，蒸发溶剂。用乙醚研磨该固体，得到纯的酰肼2，收率为86％/月。用CS2和KOH在60℃下处理酰肼2 18小时，在真空浓缩后产生固体。发现该物质可以通过用H 2 O研磨然后过滤而容易地纯化，得到硫醇3，产率为78％，因此在前两个步骤中避免了色谱法。这种操作简单的程序为子序列聚焦的文库合成提供了多克量的3。最后，通过使用K 2 CO 3作为碱，在室温DMF中通过硫醇3与取代的芳基溴化物的亲核置换反应实现芳环的多样化。

86%

With hydrazine hydrate In ethanol for 10.25 h; Cooling with ice; Reflux

将异烟酸乙酯1（1.5g，10mmol）溶于15mL乙醇中，然后在冰冷却下缓慢滴加水合肼（2g，40mmol），加完后，在室温下搅拌15min，然后在回流下加热10小时。反应完成后，通过旋转蒸发除去乙醇，倒入水中，用乙酸乙酯萃取，将有机相干燥并浓缩，得到所需产物2（1.2g，86％），不经纯化进入下一步骤。

85%

With hydrazine hydrate In ethanol for 24 h; Reflux

步骤1：将15.12g（0.1mol）乙基吡啶-4-羧酸酯和10.00g（0.2mol）水合肼（NH 2 NH 2·H 2 O）加入到50mL乙醇中，回流24小时，冷却在室温下，将溶液旋转干燥并重结晶。得到11.62g（0.085mol）吡啶-4-甲酰基氢化物，收率85％。

73%

With hydrazine hydrate In ethanol for 6 h; Reflux

向异烟酸乙酯（1.44g，10mmol）的EtOH（10mL）溶液中滴加85％的水合肼（2mL，35mmol）。将混合物在回流下加热6小时。反应结束后，将混合物冷却至室温，过滤，用冷乙酸乙酯洗涤，然后干燥，得到白色固体异烟肼2，收率（1.0g，73％）。

73%

With hydrazine hydrate In water for 6 h;

将异烟酸乙酯（1.44g，10mmol）和85％水合肼（2mL，35mmol）的混合物在回流下加热6小时。将混合物冷却至室温，过滤，用冷乙酸乙酯洗涤，然后干燥，得到白色固体异烟酰肼2.产量1.0g，73％。

12.9 g

With hydrazine hydrate In ethanol for 3 h; Reflux

一般步骤：将水杨酸（13.8g; 0.1mol）和强酸性离子交换树脂Amberlyst-15（5g）的乙醇（300ml）悬浮液在回流下搅拌3天。过滤分离不溶性催化剂，和洗过的乙醇（3 20毫升）。将合并的乙醇滤液与水合肼（20ml; 20.5g; 0.4mol）混合，并使用改进的Hickman蒸馏装置（方案3）以缓慢溶剂蒸馏回流。回流3小时后，将反应混合物的体积减少至约50ml，开始形成白色沉淀。将白色悬浮液冷却至室温，然后在5℃下放置1小时。过滤分离不溶物，用冰冷的乙醇洗涤，空气干燥，得到纯产物（13.2g; 87％）。

参考文献：

[1] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2015, vol. 54B, # 10, p. 1260 - 1274
[2] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 6, p. 1532 - 1537
[3] Patent: US2015/210679, 2015, A1. Location in patent: Paragraph 0091
[4] Patent: US2016/214969, 2016, A1. Location in patent: Paragraph 0076-0077
[5] Patent: CN105481765, 2016, A. Location in patent: Paragraph 0030; 0031; 0032
[6] Patent: CN104892639, 2018, B. Location in patent: Paragraph 0052; 0053; 0054; 0066; 0067; 0068; 0069
[7] Heterocycles, 2006, vol. 68, # 8, p. 1585 - 1594
[8] Medicinal Chemistry Research, 2013, vol. 22, # 10, p. 4953 - 4963
[9] Letters in Drug Design and Discovery, 2014, vol. 11, # 9, p. 1107 - 1111
[10] Letters in Drug Design and Discovery, 2014, vol. 11, # 9, p. 1119 - 1123
[11] Monatshefte fuer Chemie, 1912, vol. 33, p. 403
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[19] Pharm. Ind., 1952, vol. 14, p. 366
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[30] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 24, p. 7246 - 7250
[31] Medicinal Chemistry Research, 2012, vol. 21, # 7, p. 1451 - 1470
[32] Medicinal Chemistry Research, 2012, vol. 21, # 8, p. 1935 - 1952,18
[33] Medicinal Chemistry Research, 2012, vol. 21, # 8, p. 1935 - 1952
[34] Journal of the Chemical Society of Pakistan, 2018, vol. 40, # 2,
[35] Medicinal Chemistry Research, 2012, vol. 21, # 11, p. 3646 - 3655
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[37] Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 8, p. 2286 - 2297
[38] European Journal of Medicinal Chemistry, 2015, vol. 102, p. 243 - 248
[39] Bioorganic Chemistry, 2018, vol. 80, p. 253 - 260
[40] ACS Medicinal Chemistry Letters, 2013, vol. 4, # 11, p. 1097 - 1101
[41] European Journal of Medicinal Chemistry, 2014, vol. 71, p. 199 - 218
[42] Dyes and Pigments, 2014, vol. 108, p. 32 - 40
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[49] Inorganica Chimica Acta, 2017, vol. 461, p. 301 - 315
[50] ChemMedChem, 2017, vol. 12, # 12, p. 972 - 985
[51] Patent: CN107011255, 2017, A. Location in patent: Paragraph 0024
[52] Chemistry and Biodiversity, 2018, vol. 15, # 9,
[53] Patent: CN105085390, 2018, B. Location in patent: Paragraph 0059-0067

2. 合成：54-85-3

2459-09-8

54-85-3

产率

合成条件

实验步骤

94.1%

With hydrazine hydrate In ethanol at 20℃; for 3 h;

将4-吡啶甲酸甲酯（2.74g，20mmol）和无水乙醇（15mL）加入到50mL圆底烧瓶中，在室温下搅拌直至固体完全溶解。少量滴加水合肼（30mmol，100％），大量加入后立即出现针状白色固体。在室温下搅拌3小时后，过滤，用少量乙醇冲洗，真空干燥，得到2.58g白色针状物，收率94.1％，

86%

With hydrazine hydrate In ethanol at 23℃; for 16 h;

i）将异烟酸甲酯（1.00mL，8.47mmol）和水合肼（1.23mL，25.4mmol）的无水乙醇（10mL）溶液在室温下搅拌16小时。浓缩并随后用甲苯和DCM共蒸发得到INT-28A（1.00g，7.31mmol，86％）。 LCMS：caic。 [M + H] = 138.07，实测值138.1。

78%

With hydrazine hydrate In methanol for 5 h; Reflux

通用方法：向适当的甲酯17（a-j）（1.0mmol）在50mL甲醇中的溶液中加入99％水合肼（4.0mmol），将混合物回流5小时直至反应完成（TLC）。反应完成后，冷却，用甲醇洗涤得到的固体。粗产物用乙醇重结晶。

75%

With hydrazine hydrate In ethanol at 150℃; for 0.08 h; Microwave irradiation

向异烟酸甲酯（100mg，0.73mmol）在0.3mL乙醇中的溶液中加入水合肼（0.35mL，7.29mmol）。将该反应混合物在微波反应器中在150℃下加热5分钟。使反应冷却至室温并用10mL MeOH稀释，然后浓缩。通过柱色谱法用MeOH / CH 2 Cl 2（1：4）纯化残余物，得到84mg（75％）标题化合物。 1 H NMR（MeOD）58.70（dd，J = 4.8,1.6Hz，2H），7.77（dd，J = 4.4,1.6Hz，2H）。计算出的C6H7N30（M + H）Vz的LRMS：137.05测得的137.1m / z。

75%

With hydrazine hydrate In ethanol at 150℃; for 0.08 h; Microwave irradiation

一个。异烟酰基肼的制备向异烟酸甲酯（100mg，0.73mmol）在0.3mL乙醇中的溶液中加入水合肼（0.35mL，7.29mmol）。将该反应混合物在微波反应器中在150℃下加热5分钟。使反应冷却至室温并用10mL MeOH稀释，然后浓缩。通过柱色谱法用MeOH / CH 2 Cl 2（1：4）纯化残余物，得到84mg（75％）所需产物。 1 H NMR（MeOD）δ8.70（dd，J = 4.8,1.6Hz，2H），7.77（dd，J = 4.4,1.6Hz，2H）。计算出的C6H7N30（M + H）Vz的LRMS：137.05测得的137.1m / z。

73%

for 6 h; Reflux

将式（II）（1.37g，10mmol）和浓度为80质量％的水合肼水溶液（2mL，35mmol）加热回流6小时，冷却至室温，过滤，滤饼用乙酸乙酯洗涤。干燥，得到如式（III）所示的异烟肼，收率（1.0g，73％）。

参考文献：

[1] Patent: CN104592217, 2018, B. Location in patent: Paragraph 0049; 0050; 0051
[2] Patent: WO2015/161928, 2015, A1. Location in patent: Page/Page column 48
[3] Medicinal Chemistry Research, 2016, vol. 25, # 4, p. 627 - 643
[4] Patent: WO2016/154471, 2016, A1. Location in patent: Paragraph 00445
[5] Patent: WO2017/11466, 2017, A1. Location in patent: Paragraph 00471
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[7] Patent: CN106699776, 2017, A. Location in patent: Paragraph 0024-0025; 0027; 0030-0031
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[20] Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 14, p. 2369 - 2374

3. 合成：54-85-3

1453-82-3

55-22-1

54-85-3

产率

合成条件

实验步骤

90.4%

With hydrazine dihydrochloride In aq. phosphate buffer at 30℃; for 1 h; Enzymatic reaction

在含有50ml反应混合物的250ml Erlenmeyer烧瓶中进行补料分批生物转化，其中初始异烟酰胺和肼-2HCl浓度分别为100和1000mM，在磷酸盐缓冲液（100mM，pH 7）中于30℃和2.0mgdcw / ml静息细胞中进行。 B.mithithii菌株IITR6b2。将粉末状异烟酰胺（0.61g）和高浓度溶液（1ml，5M，pH 7）的肼-2HCl以60分钟的间隔加入随后的7次进料中，以分别限制残留的异烟酰胺和肼-2HCl浓度分别高于100和1000mM。在反应过程中每30分钟取出500μl样品，并监测异烟肼，异烟酸和异烟酰胺的浓度。努力使反应体积保持在50ml左右。对于任何自发的化学反应，也使用相同的参数进行对照实验而没有酶

参考文献：

[1] Journal of Molecular Catalysis B: Enzymatic, 2013, vol. 97, p. 67 - 73

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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：54-85-3

1570-45-2

54-85-3

产率

合成条件

实验参考步骤

86%

With hydrazine hydrate In ethanol at 60℃; for 1 h;

86%

With hydrazine hydrate In ethanol at 60℃; for 1 h;

86%

With hydrazine hydrate In ethanol for 10.25 h; Cooling with ice; Reflux

85%

With hydrazine hydrate In ethanol for 24 h; Reflux

73%

With hydrazine hydrate In ethanol for 6 h; Reflux

73%

With hydrazine hydrate In water for 6 h;

12.9 g

With hydrazine hydrate In ethanol for 3 h; Reflux

参考文献：

2. 合成：54-85-3

2459-09-8

54-85-3

产率

合成条件

实验参考步骤

94.1%

With hydrazine hydrate In ethanol at 20℃; for 3 h;

86%

With hydrazine hydrate In ethanol at 23℃; for 16 h;

78%

With hydrazine hydrate In methanol for 5 h; Reflux

75%

With hydrazine hydrate In ethanol at 150℃; for 0.08 h; Microwave irradiation

75%

With hydrazine hydrate In ethanol at 150℃; for 0.08 h; Microwave irradiation

73%

for 6 h; Reflux

参考文献：

3. 合成：54-85-3

1453-82-3

55-22-1

54-85-3

产率

合成条件

实验参考步骤

90.4%

With hydrazine dihydrochloride In aq. phosphate buffer at 30℃; for 1 h; Enzymatic reaction

参考文献：

[1] Journal of Molecular Catalysis B: Enzymatic, 2013, vol. 97, p. 67 - 73

4. 合成：54-85-3

1453-82-3

54-85-3

产率

合成条件

实验参考步骤

97.34%

at 115℃; for 4 h;

将9.9918克异烟酰胺溶于77.97克无水乙醇中，并向其中加入10.1克水合肼（100％）。将反应混合物在甘油浴中在115摄氏度下回流4小时; 蒸馏除去醇和固体物质，在热条件下取出异烟酸酰肼（INH）回收的异烟酰肼为9.727gms，即97.34wt％，得到的熔点为170℃，实际为169.9℃。

97.34%

at 115℃; for 4 h; Heating / reflux

将9.9918克异烟酰胺溶解在77.97克无水乙醇中，并向其中加入10.1克水合肼（100％）。将反应混合物在甘油浴中在115摄氏度下回流4小时; 然后蒸馏出醇和固体物质，在热条件下取出异烟酸酰肼（INH）。回收的异烟酸酰肼为9.727克。即得到97.34％（重量），熔点为170℃，实际为169.9℃。

96.03%

With hydrazine In methanol at 110℃; for 4 h;

将19.3989克异烟酰胺溶于39.488克甲醇中，并向其中加入14.14克水合肼（100％）。将反应混合物在甘油浴中在110摄氏度下回流4小时;然后蒸馏出醇和固体物质，在热条件下取出异烟酸酰肼（INH）。回收的异烟酸酰肼为19.3克，即99.49重量％，得到的熔点为169.9℃，相对于170℃实际。实施例-3将24.99克异烟酰胺溶于39.48克甲醇和20.20克向其中加入水合肼（100％）。将反应混合物在甘油浴中在110摄氏度下回流4小时;然后蒸馏出醇和固体物质，在热条件下取出异烟酸酰肼（INH）。回收的异烟酸酰肼为24.0克，即96.03重量％，得到的熔点为169.9℃，实际为170℃。

96.03%

With hydrazine In methanol at 110℃; for 4 h; Heating / reflux

将19.3989克异烟酰胺溶于39.488克甲醇中，并向其中加入14.14克水合肼（100％）。将反应混合物在甘油浴中在110摄氏度下回流4小时; 然后蒸馏出醇和固体物质，在热条件下取出异烟酸酰肼（INH）。回收的异烟酸酰肼为19.3克。即得到99.49％（重量），熔点为169.9℃，实际为170℃。实施例-3将24.99克异烟酰胺溶于39.48克甲醇中，并向其中加入20.20克水合肼（100％）。将反应混合物在甘油浴中在110摄氏度下回流4小时; 然后蒸馏出醇和固体物质，在热条件下取出异烟酸酰肼（INH）。回收的异烟酸酰肼为24.0克。即得到96.03％（重量），熔点为169.9°C，实际为170°C。

129.3 g

With butan-2-one azine In water at 160 - 170℃; Green chemistry

将异烟酰胺搅拌成123g，温度计和回流冷凝器，接收器的上部用导管连接以吸收氨气;打开搅拌，加热至160~170，异烟酰胺熔化成液体后，加入丁酮和氮气将260g和水90g缓慢加入异烟酰胺中，控制反应温度160~170℃，将冷凝器出口温度控制在75~80℃，加入丁醇，回流比R = 1~10，回收氨气;丁酮用氮和水滴加时间控制在1~2h，孵育反应完成30min后，再升温至180°C~190°C未反应的丁酮氮蒸馏回收，冷却后丁酮氮回收冷却，固体物质将在四颈烧瓶中沉淀的过滤，洗涤，干燥后，得到129.3g异烟肼。

参考文献：

[1] Patent: US6734309, 2004, B1. Location in patent: Page column 2
[2] Patent: WO2004/56778, 2004, A1. Location in patent: Page 3
[3] Patent: US6734309, 2004, B1. Location in patent: Page column 2; 3
[4] Patent: WO2004/56778, 2004, A1. Location in patent: Page 3
[5] Russian Journal of Physical Chemistry, 1993, vol. 67, # 5, p. 976 - 977
[6] Zhurnal Fizicheskoi Khimii, 1993, vol. 67, # 5, p. 1083 - 1085
[7] Russian Journal of Physical Chemistry, 1993, vol. 67, # 5, p. 976 - 977
[8] Zhurnal Fizicheskoi Khimii, 1993, vol. 67, # 5, p. 1083 - 1085
[9] Yakugaku Zasshi, 1957, vol. 77, p. 219
[10] Chem.Abstr., 1957, p. 11341
[11] Patent: CN106866522, 2017, A. Location in patent: Paragraph 0006; 0009

5. 合成：54-85-3

13841-66-2

54-85-3

产率

合成条件

实验参考步骤

74.1%

With hydrazine hydrate In ethanol for 6 h; Reflux

一般步骤：将获得的化合物II用乙醇（90mL）和水合肼（85％，30mL）溶解，然后将混合物加热回流6小时。反应完成后，在减压下蒸馏出乙醇和过量的水合肼，并留下白色产物。将粗产物从乙醇中重结晶，得到白色晶体III。

参考文献：

[1] Pharmaceutical Chemistry Journal, 1980, vol. 14, # 3, p. 199 - 202
[2] Khimiko-Farmatsevticheskii Zhurnal, 1980, vol. 14, # 3, p. 93 - 96
[3] Russian Journal of General Chemistry, 2015, vol. 85, # 3, p. 746 - 751

6. 合成：54-85-3

55-22-1

54-85-3

参考文献：

[1] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2010, vol. 49, # 4, p. 526 - 531
[2] Asian Journal of Chemistry, 2011, vol. 23, # 6, p. 2648 - 2652
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[4] Chem.Abstr., 1958, p. 7315
[5] Acta Chemica Scandinavica (1947-1973), 1957, vol. 11, p. 1787
[6] Patent: US2891067, 1957,
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[9] Phosphorus, Sulfur and Silicon and the Related Elements, 2006, vol. 181, # 9, p. 2079 - 2087
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[11] Acta Chimica Academiae Scientiarum Hungaricae, 1958, vol. 14, p. 197,199
[12] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 1, p. 184 - 187
[13] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 21, p. 6225 - 6229
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[15] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 24, p. 7246 - 7250
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[17] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 11, p. 3615 - 3621
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[52] Patent: DE1116667, 1956,

7. 合成：54-85-3

100-48-1

54-85-3

1453-82-3

参考文献：

[1] Molecules, 2000, vol. 5, # 2, p. 118 - 126

8. 合成：54-85-3

90322-87-5

54-85-3

参考文献：

[1] RSC Advances, 2015, vol. 5, # 118, p. 97089 - 97101

9. 合成：54-85-3

14254-57-0

54-85-3

参考文献：

[1] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2013, vol. 52, # 10, p. 1318 - 1324
[2] Patent: CN107011255, 2017, A

10. 合成：54-85-3

100-48-1

54-85-3

参考文献：

[1] Patent: US2830994, 1956,

11. 合成：54-85-3

108-89-4

54-85-3

参考文献：

[1] Patent: CN107011255, 2017, A

12. 合成：54-85-3

88057-93-6

54-85-3

31599-25-4

参考文献：

[1] Acta Poloniae Pharmaceutica, 1993, vol. 50, # 2.3, p. 183 - 188

13. 合成：54-85-3

17332-42-2

54-85-3

31599-25-4

参考文献：

[1] Acta Poloniae Pharmaceutica, 1993, vol. 50, # 2.3, p. 183 - 188

14. 合成：54-85-3

N/A

54-85-3

参考文献：