[ CAS No. 54231-32-2 ]

Name: 54231-32-2|3-Chloro-2-nitropyridine|98%
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Quality Control of [ 54231-32-2 ]

COA NMR CNMR HPLC LC-MS

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Product Details of [ 54231-32-2 ]

CAS No. :	54231-32-2	MDL No. :	MFCD00490110
Formula :	C₅H₃ClN₂O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	PSGASDJUCYTRAD-UHFFFAOYSA-N
M.W :	158.54	Pubchem ID :	554988
Synonyms :

Calculated chemistry of [ 54231-32-2 ]

Physicochemical Properties

Num. heavy atoms :	10
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	3.0
Num. H-bond donors :	0.0
Molar Refractivity :	38.07
TPSA :	58.71 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.1 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.19
Log Po/w (XLOGP3) :	1.64
Log Po/w (WLOGP) :	1.64
Log Po/w (MLOGP) :	0.68
Log Po/w (SILICOS-IT) :	-0.09
Consensus Log Po/w :	1.01

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-2.23
Solubility :	0.925 mg/ml ; 0.00583 mol/l
Class :	Soluble
Log S (Ali) :	-2.49
Solubility :	0.518 mg/ml ; 0.00327 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.01
Solubility :	1.55 mg/ml ; 0.00979 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.91

Safety of [ 54231-32-2 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 54231-32-2 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 54231-32-2 ]
Downstream synthetic route of [ 54231-32-2 ]

[ 54231-32-2 ] Synthesis Path-Upstream 1~6

1
[ 54231-32-2 ]
[ 39620-04-7 ]

Yield	Reaction Conditions	Operation in experiment
63%	Stage #1: With hydrogenchloride; tin(ll) chloride In methanol; water at 20℃; Stage #2: With sodium hydroxide In methanol; water; ethyl acetate	A sample of 3-chloro-2-nitropyridine (1.00 g, 6.31 mmol) was dissolved in methanol (10 mL), treated with Tin(II) chloride (5.98 g, 31.54 mmol) followed by concentrated HCl (2.63 mL, 31.54 mmol). The reaction mixture was allowed to stir overnight at rt. The solution was then diluted with ethyl acetate and washed with IN NaOH solution. The organic phase was then washed with concentrated NaHCO₃ solution and dried over Na₂SO₄. Concentration in vacuo gave the title compound (510.0mg, 63percent). ¹H NMR (400 MHz, CD₃CN) δ 6.80 (m, 1 H), 7.60 (d, 1 H), 8.12 (d, 1 H).
41%	With hydrogenchloride; iron In ethanol; water at 0 - 20℃; for 2.5 h;	To a stirred solution of 3-chloro-2-nitropyridine (1.00 g, 6.31 mmol) in EtOH (13 ml) were added a 2 M HCl aqueous solution (1.30 ml, 2.60 mmol) and iron (2.37 g, 42.4 mmol) at 0° C. The resulting mixture was stirred for 2.5 h at room temperature. Celite (2.40 g) was added. The mixture was filtered over a celite pad and evaporated to give a dark oil that was purified by elution through a SCX cartridge. The title compound D54 (0.34 g, 2.59 mmol, 41percent yield) was obtained as a dark solid. UPLC: rt=0.27 min, peaks observed: 129 (M+1, 100percent) and 131 (M+1, 33percent). C₅H₅ClN₂requires 128.

Reference： [1] Patent: WO2006/44775, 2006, A2, . Location in patent: Page/Page column 64
[2] Patent: US2009/22670, 2009, A1, . Location in patent: Page/Page column 25

2
[ 54231-32-2 ]
[ 42753-67-3 ]

Reference： [1] Patent: WO2013/117649, 2013, A1,

3
[ 54231-32-2 ]
[ 22841-92-5 ]

Reference： [1] Journal of Heterocyclic Chemistry, 1989, vol. 26, p. 475 - 476

4
[ 54231-32-2 ]
[ 39968-33-7 ]

Reference： [1] Journal of the Chemical Society of Pakistan, 2011, vol. 33, # 3, p. 324 - 332

5
[ 54231-32-2 ]
[ 1480-64-4 ]

Reference： [1] Journal of Organic Chemistry, 2015, vol. 80, # 24, p. 12137 - 12145

6
[ 13269-19-7 ]
[ 54231-32-2 ]

Reference： [1] Organic Process Research and Development, 2017, vol. 21, # 1, p. 44 - 51

[ 54231-32-2 ] Synthesis Path-Downstream 1~68

1
[ 54231-32-2 ]
[ 4043-87-2 ]
[ 89860-69-5 ]

Yield	Reaction Conditions	Operation in experiment
55%	With sodium hydrogencarbonate In ethanol for 5h; Heating;

Reference： [1]Adegoke, E. A.; Alo, Babajide [Journal of Heterocyclic Chemistry, 1983, vol. 20, p. 1509 - 1512]

2
[ 54231-32-2 ]
[ 22841-92-5 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrazine hydrate In ethanol

Reference： [1]Ple, N.; Queguiner, G. [Journal of Heterocyclic Chemistry, 1989, vol. 26, p. 475 - 476]

3
[ 54231-32-2 ]
[ 147-85-3 ]
[ 89860-68-4 ]

Yield	Reaction Conditions	Operation in experiment
53%	With sodium hydrogencarbonate In ethanol for 5h; Heating;

Reference： [1]Adegoke, E. A.; Alo, Babajide [Journal of Heterocyclic Chemistry, 1983, vol. 20, p. 1509 - 1512]

4
[ 54231-32-2 ]
3-(4-Aminomethyl-benzoyl)-4-chloro-indole-1-carboxylic acid dimethylamide [ No CAS ]
4-Chloro-3-{4-[(2-nitro-pyridin-3-ylamino)-methyl]-benzoyl}-indole-1-carboxylic acid dimethylamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In acetonitrile a) RT, 30 min, b) 60 deg C, 2 h;

Reference： [1]Curtin, Michael L.; Davidsen, Steven K.; Heyman, H. Robin; Garland, Robert B.; Sheppard, George S.; Florjancic, Alan S.; Xu, Lianhong; Carrera Jr., George M.; Steinman, Douglas H.; Trautmann, Jeff A.; Albert, Daniel H.; Magoc, Terrance J.; Tapang, Paul; Rhein, David A.; Conway, Richard G.; Luo, Gongjin; Denissen, Jon F.; Marsh, Kennan C.; Morgan, Douglas W.; Summers, James B. [Journal of Medicinal Chemistry, 1998, vol. 41, # 1, p. 74 - 95]

5
[ 110-89-4 ]
[ 54231-32-2 ]
2'-nitro-3,4,5,6-tetrahydro-2<i>H</i>-[1,3']bipyridinyl [ No CAS ]
[ 26930-71-2 ]
[ 282723-20-0 ]

Yield	Reaction Conditions	Operation in experiment
1: 58 % Spectr. 2: 18 % Spectr. 3: 24 % Spectr.	With TEA In dimethyl sulfoxide at 90℃; for 4h;

Reference： [1]Yao, Jiangchao; Blake, Paul R.; Yang, Ji [Heterocycles, 2005, vol. 65, # 9, p. 2071 - 2081]

6
[ 54231-32-2 ]
[ 103-84-4 ]
2-methyl-1-phenyl-1H-imidazo[4,5-b]pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
43%		26 Example 26 Method A applied to 3-chloro-2-nitropyridine (79 mg) and N-phenylacetamide (81 mg, 0.6 mmol) afforded the title compound as brown viscous oil (45 mg, 43% yield). 1H NMR (DMSO) δ 2.54 (s, 3 H), 7.35-7.68 (m, 6 H), 7.77 (d, J = 8.8 Hz, 1 H), 8.58 (br s, 1 H); 13C NMR δ 14.0, 118.9, 120.1, 126.8, 128.5, 129.6, 130.1, 133.9, 143.0, 151.6, 156.7. HRMS (FAB): calculated for C13H12N3 [M+H+]: 210.1031; found: 210.1026.
	Multi-step reaction with 2 steps 1: palladium(II) trifluoroacetate; caesium carbonate; (R)-2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl / toluene / 18 h / 80 °C / Inert atmosphere 2: iron; acetic acid / 0.5 h / Reflux

Reference： [1]Current Patent Assignee: SANOFI - EP1878724, 2008, A1 Location in patent: Page/Page column 22
[2]Alonso, Jorge; Halland, Nis; Nazare, Marc; R'Kyek, Omar; Urmann, Matthias; Lindenschmidt, Andreas [European Journal of Organic Chemistry, 2011, # 2, p. 234 - 237]

7
[ 54231-32-2 ]
[ 38042-20-5 ]
C₁₀H₁₂N₂OS [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 80℃; for 0.166667h; Irradiation;

Reference： [1]Ma, Chen; Zhang, Qun; Ding, Kai; Xin, Liang; Zhang, Dongju [Tetrahedron Letters, 2007, vol. 48, # 42, p. 7476 - 7479]

8
[ 54231-32-2 ]
[ 20284-97-3 ]
C₁₃H₁₆N₂OS [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 80℃; for 0.166667h; Irradiation;

Reference： [1]Ma, Chen; Zhang, Qun; Ding, Kai; Xin, Liang; Zhang, Dongju [Tetrahedron Letters, 2007, vol. 48, # 42, p. 7476 - 7479]

9
C₉H₁₇NOS [ No CAS ]
[ 54231-32-2 ]
C₁₄H₁₈N₂OS [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 80℃; for 0.166667h; Irradiation;

Reference： [1]Ma, Chen; Zhang, Qun; Ding, Kai; Xin, Liang; Zhang, Dongju [Tetrahedron Letters, 2007, vol. 48, # 42, p. 7476 - 7479]

10
C₇H₁₃NO₂S [ No CAS ]
[ 54231-32-2 ]
C₁₂H₁₄N₂O₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 80℃; for 0.166667h; Irradiation;

Reference： [1]Ma, Chen; Zhang, Qun; Ding, Kai; Xin, Liang; Zhang, Dongju [Tetrahedron Letters, 2007, vol. 48, # 42, p. 7476 - 7479]

11
[ 54231-32-2 ]
[ 1009-79-6 ]
C₁₄H₁₂N₂OS [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 80℃; for 0.166667h; Irradiation;

Reference： [1]Ma, Chen; Zhang, Qun; Ding, Kai; Xin, Liang; Zhang, Dongju [Tetrahedron Letters, 2007, vol. 48, # 42, p. 7476 - 7479]

12
[ 54231-32-2 ]
thioglycolic acid 2-phenylethylamide [ No CAS ]
C₁₅H₁₄N₂OS [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 80℃; for 0.166667h; Irradiation;

Reference： [1]Ma, Chen; Zhang, Qun; Ding, Kai; Xin, Liang; Zhang, Dongju [Tetrahedron Letters, 2007, vol. 48, # 42, p. 7476 - 7479]

13
C₁₀H₁₃NOS [ No CAS ]
[ 54231-32-2 ]
C₁₅H₁₄N₂OS [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 80℃; for 0.166667h; Irradiation;

Reference： [1]Ma, Chen; Zhang, Qun; Ding, Kai; Xin, Liang; Zhang, Dongju [Tetrahedron Letters, 2007, vol. 48, # 42, p. 7476 - 7479]

14
[ 54231-32-2 ]
[ 75484-01-4 ]
1-(3,4-dimethoxyphenethyl)-1H-pyrido[2,3-b][1,4]thiazin-2(3H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 80℃; for 0.166667h; Irradiation;

Reference： [1]Ma, Chen; Zhang, Qun; Ding, Kai; Xin, Liang; Zhang, Dongju [Tetrahedron Letters, 2007, vol. 48, # 42, p. 7476 - 7479]

15
[ 54231-32-2 ]
[ 4822-44-0 ]
C₁₃H₁₀N₂OS [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
42%	With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 80℃; for 0.166667h; Irradiation;

Reference： [1]Ma, Chen; Zhang, Qun; Ding, Kai; Xin, Liang; Zhang, Dongju [Tetrahedron Letters, 2007, vol. 48, # 42, p. 7476 - 7479]

16
[ 54231-32-2 ]
6-aza-1,2,3,3a-tetrahydropyrrolo<1,2-a>quinoxalin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 53 percent / sodium hydrogen carbonate / ethanol / 5 h / Heating 2: conc. sulphuric acid / 8 h / Heating 3: 51 percent / 10percent Pd on charcoal / cyclohexene; ethanol / 2 h / Heating

Reference： [1]Adegoke, E. A.; Alo, Babajide [Journal of Heterocyclic Chemistry, 1983, vol. 20, p. 1509 - 1512]

17
[ 54231-32-2 ]
[ 89860-70-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 53 percent / sodium hydrogen carbonate / ethanol / 5 h / Heating 2: conc. sulphuric acid / 8 h / Heating

Reference： [1]Adegoke, E. A.; Alo, Babajide [Journal of Heterocyclic Chemistry, 1983, vol. 20, p. 1509 - 1512]

18
[ 54231-32-2 ]
[ 89860-71-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 55 percent / sodium hydrogen carbonate / ethanol / 5 h / Heating 2: 80 percent / conc. sulphuric acid / 8 h / Heating

Reference： [1]Adegoke, E. A.; Alo, Babajide [Journal of Heterocyclic Chemistry, 1983, vol. 20, p. 1509 - 1512]

19
[ 54231-32-2 ]
[ 54231-44-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: methanol / Heating 2: aq. HCl / Heating

Reference： [1]Azev,Yu.A. et al. [Chemistry of Heterocyclic Compounds, 1974, vol. 10, p. 687 - 690][Khimiya Geterotsiklicheskikh Soedinenii, 1974, vol. 6, p. 792 - 795]

20
[ 54231-32-2 ]
[ 54231-45-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: methanol / Heating 2: aq. HBr / Heating

Reference： [1]Azev,Yu.A. et al. [Chemistry of Heterocyclic Compounds, 1974, vol. 10, p. 687 - 690][Khimiya Geterotsiklicheskikh Soedinenii, 1974, vol. 6, p. 792 - 795]

21
[ 54231-32-2 ]
[ 39620-04-7 ]

Yield	Reaction Conditions	Operation in experiment
63%		A sample of 3-chloro-2-nitropyridine (1.00 g, 6.31 mmol) was dissolved in methanol (10 mL), treated with Tin(II) chloride (5.98 g, 31.54 mmol) followed by concentrated HCl (2.63 mL, 31.54 mmol). The reaction mixture was allowed to stir overnight at rt. The solution was then diluted with ethyl acetate and washed with IN NaOH solution. The organic phase was then washed with concentrated NaHCO3 solution and dried over Na2SO4. Concentration in vacuo gave the title compound (510.0mg, 63%). 1H NMR (400 MHz, CD3CN) delta 6.80 (m, 1 H), 7.60 (d, 1 H), 8.12 (d, 1 H).
41%	With hydrogenchloride; iron; In ethanol; water; at 0 - 20℃; for 2.5h;	To a stirred solution of 3-chloro-2-nitropyridine (1.00 g, 6.31 mmol) in EtOH (13 ml) were added a 2 M HCl aqueous solution (1.30 ml, 2.60 mmol) and iron (2.37 g, 42.4 mmol) at 0 C. The resulting mixture was stirred for 2.5 h at room temperature. Celite (2.40 g) was added. The mixture was filtered over a celite pad and evaporated to give a dark oil that was purified by elution through a SCX cartridge. The title compound D54 (0.34 g, 2.59 mmol, 41% yield) was obtained as a dark solid. UPLC: rt=0.27 min, peaks observed: 129 (M+1, 100%) and 131 (M+1, 33%). C5H5ClN2 requires 128.

Reference： [1]Patent: WO2006/44775,2006,A2 .Location in patent: Page/Page column 64
[2]Patent: US2009/22670,2009,A1 .Location in patent: Page/Page column 25

22
[ 1914-02-9 ]
[ 54231-32-2 ]
[ 870072-64-3 ]

Yield	Reaction Conditions	Operation in experiment
18%	at 220℃; for 0.25h;Microwave irradiation;	4a. 3,3-dimethyl-1-(3-nitropyridin-2-yl)indoline:; To 2a (90 mg, 0.61 mmol) was added 2-nitro-3-chloropyridine (200 mg, 1.26 mmol). The reaction mixture was heated at 220 C. microwave for 15 min. The desired compound was isolated via preparative HPLC to afford 4a (30 mg, 18%) as white lyophilizes. Column: Luna 25×100 mm; Eluted from 35% CH3CN to 100% CH3CN in H2O with 0.1% TFA MS (ES) m/z 269 [M+H]+.

Reference： [1]Patent: US2006/293281,2006,A1 .Location in patent: Page/Page column 72-73

23
[ 54231-32-2 ]
[ 108-98-5 ]
[ 953045-26-6 ]

Yield	Reaction Conditions	Operation in experiment
69.8%	With caesium carbonate In dimethyl sulfoxide at 20℃; for 1.5h;	180.A Step A: Preparation of 2-nitro-3-(phenylthio)pyridine: 3-chloro-2-nitropyridine (30.6 g, 193 mmol) was dissolved in DMSO (200 mL). Benzenethiol (20.7 mL, 203 mmol) was added followed by cesium carbonate (69.3 g, 212 mmol) and stirred at ambient temperature for 1.5 hours. The solution was diluted with water (750 mL) and the solids filtered. The crude material was recrystallized from EtOAc (400 mL) and with adding hexanes (1L) to give an A-crop of 23.5 g. The filtrate was concentrated and recrystallized from EtOAc/hexanes to give 7.87 g. The solids were dried on high vacuum to provide the title compound (31.38 g, 69.8% yield).
69.8%	With caesium carbonate In dimethyl sulfoxide at 20℃; for 1.5h;	2.D Preparation of 2-nitro-3-(phenylthio^)pyridine: 3-chloro-2- nitropyridine (30.6 g, 193 mmol) was dissolved in DMSO (200 mL). Benzenethiol (20.7 mL, 203 mmol) was added followed by cesium carbonate (69.3 g, 212 mmol) and stirred at ambient temperature for 1.5 hours. The solution was diluted with water (750 mL) and the resultant solids filtered. The crude material was recrystallized from EtOAc (400ml) and with adding hexanes (IL) to give an A-crop of 23.5 g. The filtrate was concentrated and recrystallized from EtOAc/hexanes to give 7.87 g. The solids were dried on high vacuum to provide the title compound (31.38 g, 69.8% yield).

Reference： [1]Current Patent Assignee: PFIZER INC - US2009/156603, 2009, A1 Location in patent: Page/Page column 85
[2]Current Patent Assignee: PFIZER INC - WO2008/118718, 2008, A2 Location in patent: Page/Page column 45-46

24
[ 54231-32-2 ]
[ 6302-65-4 ]
[ 953045-58-4 ]

Yield	Reaction Conditions	Operation in experiment
84.1%	With caesium carbonate; In dimethyl sulfoxide; at 20℃; for 1.5h;	Step A: Preparation of methyl 4-(2-nitropyridin-3-ylthio)benzoate: Stirred a mixture of <strong>[6302-65-4]methyl 4-mercaptobenzoate</strong> (4.46 g, 26.5 mmol), 3-chloro-2-nitropyridine (4.00 g, 25.2 mmol) and cesium carbonate (9.04 g, 27.8 mmol) in DMSO (60 mL) at ambient temperature for 90 minutes. The solution was diluted with water, extracted with EtOAc, dried, and concentrated. The crude solid was suspended in MeOH (80 mL) and triturated for 0.5 hours. The solid was filtered and dried to provide the title compound (6.16 g, 84.1% yield).

Reference： [1]Patent: US2009/156603,2009,A1 .Location in patent: Page/Page column 119

25
[ 54231-32-2 ]
[ 10111-08-7 ]
[ 1252799-11-3 ]

Reference： [1]European Journal of Organic Chemistry,2010,p. 4832 - 4840

26
[ 54231-32-2 ]
[ 103-84-4 ]
C₁₃H₁₁N₃O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With palladium(II) trifluoroacetate; caesium carbonate; (R)-2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl In toluene at 80℃; for 18h; Inert atmosphere;

Reference： [1]Alonso, Jorge; Halland, Nis; Nazare, Marc; R'Kyek, Omar; Urmann, Matthias; Lindenschmidt, Andreas [European Journal of Organic Chemistry, 2011, # 2, p. 234 - 237]

27
[ 54231-32-2 ]
[ 372-39-4 ]
[ 1338483-78-5 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3-chloro-2-nitropyridine; 3,5-difluoroaniline With caesium carbonate In ISOPROPYLAMIDE for 0.25h; Inert atmosphere; Stage #2: With 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In ISOPROPYLAMIDE at 100℃; for 12h;	57 To a degassed solution of 3-chloro-2-nitro-pyridine (1.35 g, 8.51 mmol) and 3,5 difluoroaniline (1.0 g, 7.74 mmol) in dimethyl acetamide (23.2 mL) was added cesium carbonate (6.34 g, 19.35 mmol) and the reaction mixture was further degassed with nitrogen for 15 min. xanthophos (267 mg, 0.46 mmol) and Pd2 (dba)3 (212 mg, 0.23 mmol) were added to the reaction mixture and stirred at 100° C. for 12 h. After completion, the reaction mixture was diluted with water (50 mL) and extracted with ethyl actate (2×25 mL). The organic layer was dried over sodium sulfate and concentrated in vacuo to get the crude material, which was purified by column chromatography using silica gel (100-200 mesh) and 0-30% EtOAc in hexane to provide (3,5-difluorophenyl)-(2-nitro-pyridin-3-yl)-amine: 1H NMR (DMSO-d6, 400 MHz) δ 6.856-6.980 (m, 3H), 7.659-7.691 (m, 1H), 8.017 (dd, J=1.6 Hz, J=1.6 Hz, 1H), 8.126-8.140 (m, 1H), 9.094 (s, 1H); LC-MS (ESI) m/z 252.0 [M+H]+.

Reference： [1]Current Patent Assignee: AMGEN INC - US2011/245257, 2011, A1 Location in patent: Page/Page column 73

28
[ 54231-32-2 ]
[ 1338483-79-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: caesium carbonate / ISOPROPYLAMIDE / 0.25 h / Inert atmosphere 1.2: 12 h / 100 °C 2.1: hydrogenchloride; tin(II) chloride dihdyrate / ethanol; water / 2 h / 75 °C

Reference： [1]Current Patent Assignee: AMGEN INC - US2011/245257, 2011, A1

29
[ 54231-32-2 ]
[ 1338483-50-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: caesium carbonate / ISOPROPYLAMIDE / 0.25 h / Inert atmosphere 1.2: 12 h / 100 °C 2.1: hydrogenchloride; tin(II) chloride dihdyrate / ethanol; water / 2 h / 75 °C 3.1: HATU / dichloromethane; N,N-dimethyl-formamide / 8 h / 20 °C 4.1: 100 °C 4.2: 12 h / 70 °C

Reference： [1]Current Patent Assignee: AMGEN INC - US2011/245257, 2011, A1

30
[ 54231-32-2 ]
[ 1338483-83-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: caesium carbonate / ISOPROPYLAMIDE / 0.25 h / Inert atmosphere 1.2: 12 h / 100 °C 2.1: hydrogenchloride; tin(II) chloride dihdyrate / ethanol; water / 2 h / 75 °C 3.1: HATU / dichloromethane; N,N-dimethyl-formamide / 8 h / 20 °C 4.1: 100 °C 4.2: 12 h / 70 °C 5.1: N-ethyl-N,N-diisopropylamine / butan-1-ol / 120 °C

Reference： [1]Current Patent Assignee: AMGEN INC - US2011/245257, 2011, A1

31
[ 54231-32-2 ]
{1-[3-(3,5-difluorophenylamino)-pyridin-2-ylcarbamoyl]-ethyl}-carbamic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: caesium carbonate / ISOPROPYLAMIDE / 0.25 h / Inert atmosphere 1.2: 12 h / 100 °C 2.1: hydrogenchloride; tin(II) chloride dihdyrate / ethanol; water / 2 h / 75 °C 3.1: HATU / dichloromethane; N,N-dimethyl-formamide / 8 h / 20 °C

Reference： [1]Current Patent Assignee: AMGEN INC - US2011/245257, 2011, A1

32
[ 54231-32-2 ]
[ 103-67-3 ]
[ 1353677-72-1 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine at 60℃; Inert atmosphere;	85.85a Example 851-ethyl-3-{4-[(1-methyl-1H-imidazo[4,5-b]pyridin-2-yl)oxy]phenyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one 85a) N-benzyl-N-methyl-2-nitropyridin-3-amine The mixture of N-methylbenzylamine (6.085 mL), TEA (13.19 μL) and 3-chloro-2-nitropyridine (5 g) was stirred at 60° C. under N2 overnight. The reaction mixture was concentrated in vacuo. The residue was purified by column chromatography (silica gel, eluted with 0%-30% EtOAc in hexane) to give N-benzyl-N-methyl-2-nitropyridin-3-amine (2.6 g) as dark yellow oil.MS (API+): [M+H]+244.1.1H NMR (300 MHz, DMSO-d6) δ 2.75 (3H, s), 4.44 (2H, s), 7.16-7.47 (5H, m), 7.51-7.62 (1H, m), 7.72-7.82 (1H, m), 7.92-8.02 (1H, m).

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - US2011/319394, 2011, A1 Location in patent: Page/Page column 77

33
[ 54231-32-2 ]
[ 56291-51-1 ]

Reference： [1]Patent: US2011/319394,2011,A1

34
[ 54231-32-2 ]
[ 50339-06-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: triethylamine / 60 °C / Inert atmosphere 2: hydrogen / palladium 10% on activated carbon / ethanol / 20 °C 3: tetrahydrofuran / 20 °C

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - US2011/319394, 2011, A1

35
[ 54231-32-2 ]
[ 1353677-71-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: triethylamine / 60 °C / Inert atmosphere 2: hydrogen / palladium 10% on activated carbon / ethanol / 20 °C 3: tetrahydrofuran / 20 °C 4: trichlorophosphate / 5 h / 100 °C 5: sodium hydride / N,N-dimethyl-formamide / 0.33 h / 180 °C

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - US2011/319394, 2011, A1

36
[ 54231-32-2 ]
[ 65550-24-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: triethylamine / 60 °C / Inert atmosphere 2: hydrogen / palladium 10% on activated carbon / ethanol / 20 °C 3: tetrahydrofuran / 20 °C 4: trichlorophosphate / 5 h / 100 °C

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - US2011/319394, 2011, A1

37
[ 54231-32-2 ]
[ 39968-33-7 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrazine hydrate In ethanol for 24h; Reflux;

Reference： [1]Location in patent: experimental part Fathalla, Magda Fouad; Khattab, Sherine Nabil [Journal of the Chemical Society of Pakistan, 2011, vol. 33, # 3, p. 324 - 332]

38
[ 54231-32-2 ]
[ 68765-56-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: N,N-dimethyl-formamide / 140 °C / Microwave irradiation 2: hydrogen / palladium on activated charcoal / ethanol / 20 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide / 3 h / 140 °C / Microwave irradiation 2: hydrogen / palladium on activated charcoal / ethanol / 20 °C / Inert atmosphere