4214-76-0|2-Amino-5-nitropyridine| Ambeed

CAS No. :	4214-76-0
Formula :	C₅H₅N₃O₂
M.W :	139.11
SMILES Code :	C1=CC(=NC=C1[N+](=O)[O-])N
MDL No. :	MFCD00006325
InChI Key :	UGSBCCAHDVCHGI-UHFFFAOYSA-N
Pubchem ID :	77888

Safety of [ 4214-76-0 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302+H312+H332-H315-H319-H335
Precautionary Statements:	P261-P280-P305+P351+P338

Calculated chemistry of [ 4214-76-0 ] Show Less

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	1.0
Molar Refractivity	37.46
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	84.73 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	0.62
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	0.65
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	0.58
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.	-0.94
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	-1.44
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	-0.11

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-1.49
Solubility	4.5 mg/ml ; 0.0324 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.	-2.01
Solubility	1.38 mg/ml ; 0.00988 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	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	-1.02
Solubility	13.3 mg/ml ; 0.0957 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.	-6.69 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: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<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)	1.98

Application In Synthesis of [ 4214-76-0 ]

* 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 [ 4214-76-0 ]
Downstream synthetic route of [ 4214-76-0 ]

[ 4214-76-0 ] Synthesis Path-Upstream 1~6

1
[ 4214-76-0 ]
[ 32046-43-8 ]

References: [1] Pharmazie, 1983, vol. 38, # 9, p. 591 - 596.

2
[ 4214-76-0 ]
[ 15862-31-4 ]

Yield	Reaction Conditions	Operation in experiment
32%	Stage #1: at 20℃; Stage #2: With sodium hydrogencarbonate In water; ethyl acetateSaturated solution	Step a: 3-Bromo-5-nitropyridin-2-amine To a solution of 5-nitro-pyridin-2-ylamine (30 g, 0.22 mol) in acetic acid (200 mL) at 10° C. was added Br₂ (38 g, 0.24 mol) dropwise. After addition, the mixture was stirred at 20° C. for 30 min. The solid was filtered and then dissolved in ethyl acetate (200 mL). The mixture was basified to pH 8-9 with saturated aqueous NaHCO₃. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (100 mL*3). The combined organic layers were washed with water, brine, dried over Na₂SO₄ and concentrated under vacuum to afford 3-bromo-5-nitropyridin-2-amine (14.8 g, 32percent). ¹H-NMR (CDCl₃, 400 MHz) δ 8.94 (d, J=2.4 Hz, 1H), 8.50 (d, J=2.4 Hz, 1H), 5.67 (brs, 2H).
31%	With N-Bromosuccinimide In toluene at 80℃; for 1 h; Inert atmosphere	General procedure: Under an Ar atmosphere, N-chlorosuccinimide (0.53 g,3.95 mmol) was added to a solution of compound 1 (0.50 g,3.59 mmol) in anhydrous toluene (7.18 mL). The resulting reactionmixture was stirred at 80 C for 1 h. The reaction mixture wascooled to room temperature and 15 mL of H2O was added to thismixture. It was then extracted with EtOAc, washed with sat.NaHCO3 solution, brine, concentrated under vacuum, and purifiedby column chromatography (KANTO 60 N, Hex/EtOAc = 80/20 to60/40) to give a yellow solid 2a (0.40 g, 2.30 mmol, 64percent).

References: [1] Patent: US2009/253736, 2009, A1, . Location in patent: Page/Page column 25.
[2] Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 14, p. 3853 - 3860.
[3] Zhurnal Russkago Fiziko-Khimicheskago Obshchestva, 1920, vol. 50, p. 494[4] Chemisches Zentralblatt, 1923, vol. 94, # III, p. 1021.
[5] Zhurnal Obshchei Khimii, 1940, vol. 10, p. 1827,1836[6] Chemisches Zentralblatt, 1940, vol. 111, # II, p. 614.

3
[ 4214-76-0 ]
[ 2032-35-1 ]
[ 25045-82-3 ]

Yield	Reaction Conditions	Operation in experiment
77.6%	Stage #1: With hydrogenchloride In ethanol at 20℃; Reflux Stage #2: at 20℃;	In a 250 mL single-necked flask, bromoacetaldehyde diethyl acetal (42.5 g, 215.7 mmol) was dissolved in 1 mol / L HCL(120 mL) and ethanol (20 mL), stirred at room temperature for 30 min, heated to reflux, stirred until the solution was clear, cooled to room temperature,Add NaHCO3 adjusted to near neutral,2-Amino-5-nitropyridine (15.0 g, 107.8 mmol) was added and reacted at room temperatureovernight. The reaction was completed, extracted with ethyl acetate (100mL × 3), the organic phase was collected and the solvent was evaporated to dryness under reduced pressure. The residue was passed through a silica gel column (PE:EA = 2: 1) to give 13.7 g of 6-nitroimidazo [1,2-a] pyridine yellow-brown crystals in a yield of 77.6percent.

References: [1] Patent: CN107129496, 2017, A, . Location in patent: Paragraph 0026-0028; 0014-0016; 0020-0022.

4
[ 4214-76-0 ]
[ 623-46-1 ]
[ 25045-82-3 ]

References: [1] Yakugaku Zasshi, 1949, vol. 69, p. 496[2] Chem.Abstr., 1950, p. 4474.

5
[ 4214-76-0 ]
[ 31040-15-0 ]

References: [1] Tetrahedron, 2015, vol. 71, # 3, p. 407 - 418.

6
[ 4214-76-0 ]
[ 956697-53-3 ]

References: [1] Patent: CN109293649, 2019, A, .
[2] Patent: CN109293649, 2019, A, .

[ 4214-76-0 ] Synthesis Path-Downstream 1~12

1
[ 4214-76-0 ]
[ 623-46-1 ]
[ 25045-82-3 ]

References: [1]Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan,1949,vol. 69,p. 496.
Chem.Abstr.,1950,p. 4474.

2
[ 4214-76-0 ]
[ 456-24-6 ]
[ 5418-51-9 ]

References: [1]Canadian Journal of Chemistry,1953,vol. 31,p. 1020,1024.

3
[ 4214-76-0 ]
[ 22353-35-1 ]

Yield	Reaction Conditions	Operation in experiment
64%	With N-chloro-succinimide; In toluene; at 80.0℃; for 1.0h;Inert atmosphere;	Under an Ar atmosphere, N-chlorosuccinimide (0.53 g,3.95 mmol) was added to a solution of compound 1 (0.50 g,3.59 mmol) in anhydrous toluene (7.18 mL). The resulting reactionmixture was stirred at 80 C for 1 h. The reaction mixture wascooled to room temperature and 15 mL of H2O was added to thismixture. It was then extracted with EtOAc, washed with sat.NaHCO3 solution, brine, concentrated under vacuum, and purifiedby column chromatography (KANTO 60 N, Hex/EtOAc = 80/20 to60/40) to give a yellow solid 2a (0.40 g, 2.30 mmol, 64%). 1HNMR (500 MHz, DMSO-d6) d (ppm) 8.84 (d, J = 2.5 Hz, 1H), 8.35(d, J = 2.5 Hz, 1H), 7.91 (brs, 1H). 13C NMR (125 MHz, DMSO-d6) d(ppm) 112.58, 132.14, 135.01, 145.25, 159.75. HRMS (ESI-TOF, m/z) Calcd. for C5H4ClN3O2Na [M+Na]+: 195.9884, 197.9856, Found:195.9878, 197.9847.

References: [1]Bioorganic and Medicinal Chemistry,2017,vol. 25,p. 3853 - 3860.
[2]Journal of the Chemical Society,1951,p. 2590,2593.
[3]Journal of the Chemical Society,1951,p. 2590,2593.
[4]Zhurnal Obshchei Khimii,1940,vol. 10,p. 1827,1836.
Chemisches Zentralblatt,1940,vol. 111,p. 614.

4
[ 4214-76-0 ]
[ 38923-13-6 ]
[ 38922-99-5 ]

References: [1]Journal of Medicinal Chemistry,1972,vol. 15,p. 982 - 985.

5
[ 4548-45-2 ]
[ 4214-76-0 ]
[ 2604-39-9 ]
[ 5418-51-9 ]
[ 27048-04-0 ]

References: [1]Journal of Organic Chemistry,1985,vol. 50,p. 484 - 487.
[2]Journal of Organic Chemistry,1985,vol. 50,p. 484 - 487.

6
[ 4214-76-0 ]
[ 24424-99-5 ]
[ 161117-88-0 ]

Yield	Reaction Conditions	Operation in experiment
80%	With dmap; In dichloromethane; at 20℃;Inert atmosphere;	5-Nitropyridin-2-amine (1 eq), Boc2O (1.2 eq), DMAP (0.2 eq) was added to aflask under nitrogen atmosphere. Dichloromethane was added at room temperature and the mixture was stirred overnight. Ethyl acetate was added to the crude, the precipitated was filtered and washed with ethyl acetate to obtain the desired tert-butyl (5-n itropyrid in-2-yl)carbam ate.HPLC-MS (method A): Rt= 2.88 mm, [M+H]+ m/z: 240.Yield: 80%.
70%		A. Synthesis of (tert-butoxy)-N-(5-nitro(2-pyridyl))carboxamide (0132) To a solution of 2-amino-5-nitropyridine (0.555 g, 4 mmol) in THF (10 mL) was added 1 M NaHMDS in THF (8 mL, 8 mmol). The resulting dark red suspension was stirred for 15 min, followed by addition of a solution of Boc anhydride (0.87 mL, 3.8 mmol) in THF (5 mL). The reaction mixture was stirred at room temp for 21 hr, dilute with EtOAc, washed with 1 N HCl and brine, dried and concentrated in vacuo to give (tert-butoxy)-N-(5-nitro(2-pyridyl))carboxamide (0.63 g, 70%). ES-MS (M+H-tBu)+ = 184.
63.9%		Synthesis of compound 223.2. To a solution of NaH (1.15g, 28.75mmol, l .Oeq.) in THF (20ml) was added 223.1 (4.0g, 28.75mmol, l .Oeq) at 0 C. the reaction mixture was stirred at room temperature for 30 minutes. Boc anhydride (6.26g, 28.75mmol, l .Oeq.) in THF(lOmL) was added to the reaction mixture at room temperature and reaction was allowed to stir for 3 hours. After completion of the reaction, mixture was poured in water and solid product was filtered, dried to get pure 223.2 (4.4 g, 63.9 %). MS(ES): m/z 239.23 [M+H]+.

62%		To 0.652 g (4.69 mmol) of 2-amino-5-nitropyridine in THF (5 mL) was added 3.5 mL of NaHMDS (2M solution in THF) at 0 C. After 20 min a solution of 1.085 g (4.97 mmol) of di-tert-butyl dicarbonate in THF (6 mL) was added and the mixture was slowly warmed to room temperature overnight. Water was added, and the mixture was extracted with EtOAc (×4). The organic layer was washed with brine, dried (Na2SO4), and concentrated. Chromatography on, silica with hexanes-EtOAc (7:3), gave 0.695 g (62% yield) of tert-butyl-5-nitropyridin-2-ylcarbamate as an orange powder: 1H NMR (CDCl3) 89.19 (dd, J=2.8, 0.5 Hz, 1H), 8.93 (br s, 1H), 8.46 (ddd, J=9.4, 2.8, 0.5 Hz, 1H), 8.20 (dd, J=9.5, 0.5 Hz, 1H), 1.59 (s, 9H); LCMS (APCI-) m/z: 238 (MH+, 100%).
62%		Example 37Synthesis of N5-[4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2,5-pyridinediamineThe compound was synthesized according to Method A.To 0.652 g (4.69 mmol) of 2-amino-5-nitropyridine in THF (5 mL) was added 3.5 mL of NaHMDS (2M solution in THF) at 0 C. After 20 min a solution of 1.085 g (4.97 mmol) of di-tert-butyl dicarbonate in THF (6 mL) was added and the mixture was slowly warmed to room temperature overnight. Water was added, and the mixture was extracted with EtOAc (×4). The organic layer was washed with brine, dried (Na2SO4), and concentrated. Chromatography on, silica with hexanes-EtOAc (7:3), gave 0.695 g (62% yield) of tert-butyl-5-nitropyridin-2-ylcarbamate as an orange powder: 1H NMR (CDCl3) δ 9.19 (dd, J=2.8, 0.5 Hz, 1H), 8.93 (br s, 1H), 8.46 (ddd, J=9.4, 2.8, 0.5 Hz, 1H), 8.20 (dd, J=9.5, 0.5 Hz, 1H), 1.59 (s, 9H); LCMS (APCI-) m/z: 238 (MH+, 100%).To 0.314 g (1.31 mmol) of the above nitro compound in THF-MeOH (16 mL, 1:1) was added 0.460 g of 10% Pd/C and the mixture was stirred under hydrogen (40 in/Hg) for 4 hrs. The reaction mixture was filtered through celite, washed with MeOH and concentrated to give 0.277 g (99% yield) of tert-butyl 5-aminopyridin-2-yl-carbamate as a white powder: 1H NMR (DMSO-d6) δ9.00 (br s, 1H), 7.62 (dd, J=2.7, 0.4 Hz, 1H), 7.39 (d, J=8.7 Hz, 1H), 6.94 (dd, J=8.7, 2.8 Hz, 1H), 4.92 (s, 2H), 1.44 (s, 9H).To 0.277 g (1.33 mmol) of the above amino compound in THF (3 mL) was added 0.61 mL of n-butyllithium (2.5 M solution in hexanes) and the mixture was stirred for 10 min. A solution of 0.176 g (0.44 mmol) of 1-[4-chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-4-methoxy-1H-benzimidazole in THF (5 mL) was added and the resulting mixture was stirred for 1 hr at room temperature. The reaction mixture was neutralized with acetic acid, diluted with water, and extracted with EtOAc. The organic layer was washed with water and aq. NH3, dried, and concentrated. Chromatography on silica, eluting with hexanes-EtOAc (7:3), then with CH2Cl2-EtOAc (3:1), gave 0.033 g (13% yield) of tert-butyl 5-[4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-1,3,5-triazin-2-yl]amino}-2-pyridinylcarbamate: 1H NMR (DMSO-d6) δ10.02 (s, 1H), 9.66 (s, 1H), 8.54 (s, 1H), 8.17-7.80 (m, 4H), 7.39 (d, J=8.7 Hz, 1H), 6.97-6.93 (m, 1H), 3.98 (s, 3H), 3.82 (s, 4H), 3.74-3.72 (m, 4H), 1.48 (s, 9H).To 0.033 g (0.06 mmol) of the above carbamate in CH2Cl2 (3 mL) was added 0.1 mL (1.30 mmol) of trifluoroacetic acid, and the mixture was stirred for 5 hrs. The reaction mixture was diluted with CH2Cl2 and aq. NH4OH, and the organic layer was washed with brine, dried (Na2SO4), and concentrated. The residue was recrystallized from EtOH/CH2Cl2 to give 0.0133 g (49% yield) of N5-[4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2,5-pyridinediamine, as a brown powder: mp 267-270 C.; 1H NMR (DMSO-d6) δ9.67-9.49 (m, 1H), 8.18-7.27 (m, 5H), 6.96 (d, J=7.6 Hz, 1H), 6.48 (d, J=8.4 Hz, 1H), 5.87-5.75 (m, 2H), 3.98 (s, 3H), 3.81 (s, 4H), 3.71 (s, 4H); HRMS (ESI) M+H+ Calcd. for C21H22F2N9O2: m/z 470.1859. Found: m/z 470.1867.
	With dmap; In dimethyl sulfoxide; at 20℃; for 48h;	Preparative Example 30aPreparation of ?e^butvK5-armno-4-methylpyridm-2-yl¥2-(fl5'.2^-2-ri-(5-cMoropyrirrudin-2- yl)piperidin-4-vncvclopropyl)ethyl>carbamate.Step 1 : fert-butyl (5-nitropyridin-2-yl')carbamate.2-Amino-5-nitropyridine (Ig, 7.2mmol) and di-tert-buty dicarbonate (2.4g, 10.8ramol) were added in DMSO (1OmL), DMAP (170mg, 1.4mmol) was added and stirred at room temperature for 2 days. Water (5OmL) was added, extracted with ethyl acetate (10OmL), second wash with Brine (5OmL). The organic phase was dried by magnesium sulfate, filtered, concentrated and purified by column chromatography through a 50 gram Biotage SNAP KP-Sil silica gel cartridge eluting with 13% ethyl acetate/hexanes to give the title compound as a white solid. LRMS calc: 239.23; obs: 262.34 (M+23), 184.14 (M-55), 166.11 (M-73).
	With lithium hexamethyldisilazane; In tetrahydrofuran; at 0 - 20℃;	PREPARATION 46 tert-Butyl 5-nitropyridin-2-ylcarbamate 200 mL of THF was added to 5-nitropyridin-2-amine (5g, 35.90 mmol). The solution was cooled to 0 C. Sodium hexamethyldisilazide (NaHMDS, 13.18 g, 71.9 mmol) in 30 mL THF was added dropwise. At the same time, di-tert-butyl dicarbonate (8.3 mL, 35.90 mmol) in 30 mL THF was added dropwise. The reaction mixture was stirred at 0 C for 15min and then warmed to room temperature. The reaction mixture stopped stirring due to salt/product formation and was left at room temperature for 20h. 150 mL 0.5N HCl was added and 150 mL ethyl acetate was added. The layers were separated. The organic layer was washed with 50 mL brine, dried with Na2SO4, filtered and evaporated to dryness. A yellow solid was isolated, which was used in the next synthetic step without further purification. LRMS (m/z): 240 (M+1)+
	With sodium hexamethyldisilazane; In tetrahydrofuran; at 0 - 20℃; for 0.25h;	200 mL of THF was added to 5-nitropyridin-2-amine (5g, 35.90 mmol). The solution was cooled to 0 C. Sodium hexamethyldisilazide (NaHMDS, 13.18 g, 71 .9 mmol) in 30 mL THF was added dropwise. At the same time, di-ie f-butyl dicarbonate (8.3 mL, 35.90 mmol) in 30 mL THF was added dropwise. The reaction mixture was stirred at 0 C for 15min and then warmed to room temperature. The reaction mixture stopped stirring due to salt/product formation and was left at room temperature for 20h. 150 mL 0.5N HCI was added and 150 mL ethyl acetate was added. The layers were separated. The organic layer was washed with 50 mL brine, dried with Na2S04, filtered and evaporated to dryness. A yellow solid was isolated, which was used in the next synthetic step without further purification.LRMS (m/z): 240 (M+1 )+
94.6 g	With dmap; triethylamine; In dichloromethane; at 20℃; for 18h;	A 3-L round-bottomed flask was charged with 5-nitro-2-pyridinamine (75.0 g, 539 mmol, Alfa Aesar, Ward Hill, MA) and 500 mL of DCM. To this was added triethylamine (82 g, 809 mmol), di-tert-butyl dicarbonate (129 g, 593 mmol, Sigma-Aldrich, St. Louis, MO), and DMAP (32.9 g, 270 mmol, Sigma- Aldrich, St. Louis, MO). After stirring at rt for 18 h, the mixture was diluted with water and the solid was collected by filtration. The yellow solid was washed with MeOH to give tert-butyl (5-nitro-2-pyridinyl)carbamate (94.6 g) as a slightly-yellow solid.
94.6 g	With dmap; triethylamine; In dichloromethane; at 20℃; for 18h;	A 3-L round-bottomed flask was charged with 5-nitro-2-pyridinamine (75.0 g, 539 mmol, Alfa Aesar, Ward Hill, MA) and 500 mL of DCM. To this was added triethylamine (82 g, 810 mmol), di-tert-butyl dicarbonate (129 g, 593 mmol, Sigma-Aldrich, St. Louis, MO), and N,N-dimethylpyridin-4-amine (32.9 g, 270 mmol, Sigma-Aldrich, St. Louis, MO). After stirring at rt for 18 h, the mixture was diluted with water and the solid was collected by filtration. The yellow solid was washed with MeOH to give tert-butyl (5-nitro-2- pyridinyl)carbamate (94.6 g) as a light yellow solid.

7
[ 4214-76-0 ]
[ 121-18-6 ]
4-chloro-3-nitro-benzenesulfonic acid; compound with 5-nitro-pyridin-2-ylamine [ No CAS ]

References: [1]Molecular Crystals and Liquid Crystals,2004,vol. 420,p. 79 - 89.

8
[ 4214-76-0 ]
[ 24242-20-4 ]

References: [1]Pharmazie,1983,vol. 38,p. 591 - 596.
[2]Hoppe-Seyler's Zeitschrift fur Physiologische Chemie,1951,vol. 288,p. 237,241.

9
[ 4214-76-0 ]
[ 30651-24-2 ]

References: [1]Pharmazie,1983,vol. 38,p. 591 - 596.
[2]Hoppe-Seyler's Zeitschrift fur Physiologische Chemie,1951,vol. 288,p. 237,241.

10
[ 4214-76-0 ]
[ 2032-35-1 ]
[ 25045-82-3 ]

Yield	Reaction Conditions	Operation in experiment
77.6%		In a 250 mL single-necked flask, bromoacetaldehyde diethyl acetal (42.5 g, 215.7 mmol) was dissolved in 1 mol / L HCL(120 mL) and ethanol (20 mL), stirred at room temperature for 30 min, heated to reflux, stirred until the solution was clear, cooled to room temperature,Add NaHCO3 adjusted to near neutral,2-Amino-5-nitropyridine (15.0 g, 107.8 mmol) was added and reacted at room temperatureovernight. The reaction was completed, extracted with ethyl acetate (100mL × 3), the organic phase was collected and the solvent was evaporated to dryness under reduced pressure. The residue was passed through a silica gel column (PE:EA = 2: 1) to give 13.7 g of 6-nitroimidazo [1,2-a] pyridine yellow-brown crystals in a yield of 77.6%.

References: [1]Patent: CN107129496,2017,A .Location in patent: Paragraph 0026-0028; 0014-0016; 0020-0022.

11
[ 456-24-6 ]
[ 4214-76-0 ]

References: [1]Organic and Biomolecular Chemistry,2018,vol. 16,p. 7564 - 7567.

12
[ 4214-76-0 ]
[ 956697-53-3 ]

References: [1]Patent: CN109293649,2019,A .
[2]Patent: CN109293649,2019,A .

Historical Records

Technical Information

• Buchwald-Hartwig C-N Bond and C-O Bond Formation Reactions • Chan-Lam Coupling Reaction • Hydride Reductions • Leuckart-Wallach Reaction • Mannich Reaction • Petasis Reaction • Preparation of Amines • Reactions of Amines • Specialized Acylation Reagents-Vilsmeier Reagent • Ugi Reaction

Related Functional Groups of
[ 4214-76-0 ]

Amines

A161702 [18344-51-9]

2-Amino-3-methyl-5-nitropyridine

Similarity: 0.91

A137410 [21901-40-6]

4-Methyl-5-nitropyridin-2-amine

Similarity: 0.88

A208233 [2586-99-4]

5-Nitropyridine-2,4-diamine

Similarity: 0.88

A269518 [4487-50-7]

4-Nitropyridin-2-amine

Similarity: 0.87

A138711 [3537-14-2]

5-Nitro-2,3-pyridinediamine

Similarity: 0.86

Nitroes

A161702 [18344-51-9]

2-Amino-3-methyl-5-nitropyridine

Similarity: 0.91

A137410 [21901-40-6]

4-Methyl-5-nitropyridin-2-amine

Similarity: 0.88

A208233 [2586-99-4]

5-Nitropyridine-2,4-diamine

Similarity: 0.88

A269518 [4487-50-7]

4-Nitropyridin-2-amine

Similarity: 0.87

A138711 [3537-14-2]

5-Nitro-2,3-pyridinediamine

Similarity: 0.86

Related Parent Nucleus of
[ 4214-76-0 ]

Pyridines

A161702 [18344-51-9]

2-Amino-3-methyl-5-nitropyridine

Similarity: 0.91

A137410 [21901-40-6]

4-Methyl-5-nitropyridin-2-amine

Similarity: 0.88

A208233 [2586-99-4]

5-Nitropyridine-2,4-diamine

Similarity: 0.88

A269518 [4487-50-7]

4-Nitropyridin-2-amine

Similarity: 0.87

A138711 [3537-14-2]

5-Nitro-2,3-pyridinediamine

Similarity: 0.86

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[ 4214-76-0 ]

Amines

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[ 4214-76-0 ]

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Product Details of [ 4214-76-0 ]

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Lipophilicity

Water Solubility

Pharmacokinetics

Druglikeness

Medicinal Chemistry

Application In Synthesis of [ 4214-76-0 ]

[ 4214-76-0 ] Synthesis Path-Upstream 1~6

[ 4214-76-0 ] Synthesis Path-Downstream 1~12

Related Products

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Technical Information

Categories

Related Functional Groups of [ 4214-76-0 ]

Amines

Nitroes

Related Parent Nucleus of [ 4214-76-0 ]

Pyridines

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Prevention

Response

Storage

Disposal

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Health hazards

Environmental hazards

Inquiry

Molarity Calculator

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Related Functional Groups of
[ 4214-76-0 ]

Related Parent Nucleus of
[ 4214-76-0 ]