26163-07-5|5-Bromo-N,N-dimethylpyridin-2-amine| Ambeed

CAS No. :	26163-07-5
Formula :	C₇H₉BrN₂
M.W :	201.06
SMILES Code :	CN(C)C1=NC=C(Br)C=C1
MDL No. :	MFCD00099486
InChI Key :	XIMCGXXYEMOWQP-UHFFFAOYSA-N
Pubchem ID :	3803041

Safety of [ 26163-07-5 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302
Precautionary Statements:	P280-P305+P351+P338

Computational Chemistry of [ 26163-07-5 ] Show Less

Physicochemical Properties

Num. heavy atoms	10
Num. arom. heavy atoms	6
Fraction Csp3	0.29
Num. rotatable bonds	1
Num. H-bond acceptors	1.0
Num. H-bond donors	0.0
Molar Refractivity	46.14
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	16.13 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.03
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	2.0
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	1.91
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.	1.65
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	1.56
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.83

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.72
Solubility	0.379 mg/ml ; 0.00189 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-1.97
Solubility	2.18 mg/ml ; 0.0108 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	-2.99
Solubility	0.204 mg/ml ; 0.00102 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	Yes
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	Yes
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.	-6.11 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	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: 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)	1.85

Application In Synthesis of [ 26163-07-5 ]

* 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.

Downstream synthetic route of [ 26163-07-5 ]

[ 26163-07-5 ] Synthesis Path-Downstream 1~55

1
[ 5683-33-0 ]
[ 26163-07-5 ]
[ 84539-28-6 ]

References: [1]Journal of Organic Chemistry,1983,vol. 48,p. 1064 - 1069.
[2]Journal of Organic Chemistry,1983,vol. 48,p. 1064 - 1069.
[3]Chemische Berichte,1928,vol. 61,p. 430.
Chemische Berichte,1929,vol. 62,p. 3053.
[4]Chemische Berichte,1928,vol. 61,p. 430.
Chemische Berichte,1929,vol. 62,p. 3053.

2
[ 77-78-1 ]
[ 26163-07-5 ]

References: [1]Chemische Berichte,1928,vol. 61,p. 430.
Chemische Berichte,1929,vol. 62,p. 3053.

3
[ 100-70-9 ]
[ 26163-07-5 ]
6-dimethylamino-3-pyridyl 2-pyridyl ketone [ No CAS ]

References: [1]Magnetic Resonance in Chemistry,1986,vol. 24,p. 897 - 899.

4
[ 100-54-9 ]
[ 26163-07-5 ]
6-dimethylamino-3-pyridyl 3-pyridyl ketone [ No CAS ]

References: [1]Magnetic Resonance in Chemistry,1986,vol. 24,p. 897 - 899.

5
[ 100-48-1 ]
[ 26163-07-5 ]
6-dimethylamino-3-pyridyl 4-pyridyl ketone [ No CAS ]

References: [1]Magnetic Resonance in Chemistry,1986,vol. 24,p. 897 - 899.

6
[ 3618-79-9 ]
[ 26163-07-5 ]
[ 84539-32-2 ]
[ 84539-33-3 ]

References: [1]Journal of Organic Chemistry,1983,vol. 48,p. 1064 - 1069.
[2]Journal of Organic Chemistry,1983,vol. 48,p. 1064 - 1069.

7
[ 26163-07-5 ]
C₁₂H₁₇ClOZn [ No CAS ]
2-(dimethylamino)-5-(4-hexyloxyphenyl)pyridine [ No CAS ]

References: [1]Tetrahedron Letters,1995,vol. 36,p. 563 - 566.

8
[ 5683-33-0 ]
[ 26163-07-5 ]

Yield	Reaction Conditions	Operation in experiment
68%	With dihydrogen peroxide; 1-butylpyridinium bromide; toluene-4-sulfonic acid; In 1,2-dimethoxyethane; at 80℃; for 24h;Schlenk technique; Inert atmosphere; Green chemistry;	General procedure: To a mixture of 2-aminopyridine (0.5 mmol, 1 equiv), p-TSA (0.4 mmol,0.8 equiv), 1-butylpyridinium bromide (1.5 mmol, 3 equiv) in a 50 mL Schlenk tube were added 1,2-dimethoxyethane (2 mL) under air. Then H2O2 (1.2 mmol, 2.4 equiv) was added. The mixture was stirred at 80C for 24 h. And then the mixture was purified by silica gel column chromatography (petroleum ether/ethyl acetate) to give the products.
64%	With N-Bromosuccinimide; In dichloromethane; for 0.166667h;	N-Bromosuccinimide (190 mmol) was added portionwise to a solution of [2- (DIMETHYLAMINO)-PYRIDINE] (200 mmol) in DCM (1.0 L). After 10 min a HPLC- MS indicated complete conversion. The solvent was removed in vacuo and the residue was purified by flash-chromatography (ethyl acetate/heptane 1: 19) to give 25.7 g [(128] mmol, [64%)] of the desired arylbromide as a white solid. LC-MS: rt = 0.46 min, [201] (M+1, ES+).
	With N-Bromosuccinimide; ammonium acetate; In acetonitrile; at 20℃;	[00158] Pyri(mi)dyl bromides were commercially available (e.g. from SigmaAldrich) (Oakville, Ontario, Canada) or were prepared from commercially available pyridines or pyrimidines (10 mmol) in MeCN (40 mL) at room temperature in the presence of NH OAc (1.0 mmol) and NBS (10.5 mmol), as suggested by Das and co-workers (Das, B.; Venkatswarlu, K.; Majhi, A.; Siddaiah, V.; Reddy, K. J. Mol. Cat. A 2007, 267, 30-33). Reactions were monitored by thin layer chromatography (TLC) and typically were complete within minutes. After removal of acetonitrile in vacuo, water was added (100 mL) and the mixture extracted with EtOAc (3 x 50 mL). Non aqueous layers were combined and washed with 50 mL brine and dried over MgS04. Products were used without further purification. [00172] Compound 27 was prepared in 94% yield from 2-(/V,/V-dimethylamino)-5- bromopyridine (prepared as in Example 5, see also: Nara, S. J.; Jha, M.; Brinkhorst, J.; Zemanek, T. J.; Pratt, D. A. J. Org. Chem. 2008, 73, 9326) and aniline (Aldrich) as outlined in Example 3.

References: [1]Green Chemistry,2018,vol. 20,p. 4448 - 4452.
[2]Tetrahedron Letters,2014,vol. 55,p. 5058 - 5061.
[3]Patent: WO2004/33418,2004,A2 .Location in patent: Page 33.
[4]Bulletin of the Chemical Society of Japan,1999,vol. 72,p. 2523 - 2535.
[5]Journal of Medicinal Chemistry,2004,vol. 47,p. 4787 - 4798.
[6]Patent: WO2012/162818,2012,A1 .Location in patent: Page/Page column 44; 50.

10
diazotized 5-amino-2-dimethylamino-pyridine [ No CAS ]
[ 26163-07-5 ]

References: [1]Chemische Berichte,1928,vol. 61,p. 430.
Chemische Berichte,1929,vol. 62,p. 3053.

11
[ 5683-33-0 ]
[ 7664-93-9 ]
[ 26163-07-5 ]
[ 84539-28-6 ]

References: [1]Chemische Berichte,1928,vol. 61,p. 430.
Chemische Berichte,1929,vol. 62,p. 3053.

12
[ 26163-07-5 ]
[ 30752-19-3 ]
2-(dimethylamino)-5-(4-hexyloxyphenyl)pyridine [ No CAS ]

References: [1]Bulletin of the Chemical Society of Japan,1999,vol. 72,p. 2523 - 2535.

13
[ 26163-07-5 ]
[ 39969-56-7 ]
2-(dimethylamino)-5-(4-propoxyphenyl)pyridine [ No CAS ]

References: [1]Bulletin of the Chemical Society of Japan,1999,vol. 72,p. 2523 - 2535.

14
[ 26163-07-5 ]
[ 5419-55-6 ]
[ 579525-46-5 ]

Yield	Reaction Conditions	Operation in experiment
		(B) 6-(di methylami no)pyridi n-3-ylboronic acid[096] A solution of <strong>[26163-07-5]5-bromo-N,N-dimethylpyridin-2-amine</strong> (500 mg, 2.5 mmol) in THF (10 mL) was treated with n-BuLi (1 .2 mL, 3 mmol) at -72 C for 2 hours.Triisopropyl borate (705 mg, 3.75 mmol) was then added dropwise. After the completion of the addition, the mixture was stirred at -72 C for an additional 1 hour and slowly warmed up and stirred at the ambient temperature overnight. MeOH was carefully added, and the volatiles were removed under reduced pressure to give the title compound. MS (m/z): 187 (M+H)+.
		A solution of <strong>[26163-07-5]5-bromo-N,N-dimethylpyridin-2-amine</strong> (500 mg, 2.5 mmol) in THF (10 mL) was treated with n-BuLi (1.2 mL, 3 mmol) at -72 C. for 2 hours. Triisopropyl borate (705 mg, 3.75 mmol) was then added dropwise. After the completion of the addition, the mixture was stirred at -72 C. for an additional 1 hour and slowly warmed up and stirred at the ambient temperature overnight. MeOH was carefully added, and the volatiles were removed under reduced pressure to give the title compound. MS (m/z): 167 (M+H)+.

References: [1]Advanced Synthesis and Catalysis,2003,vol. 345,p. 620 - 624.
[2]Patent: WO2012/167423,2012,A1 .Location in patent: Page/Page column 36.
[3]Patent: US2014/121200,2014,A1 .Location in patent: Paragraph 0168; 0170.

15
[ 26163-07-5 ]
[ 68-12-2 ]
[ 149805-92-5 ]

References: [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 4787 - 4798.

16
[ 26163-07-5 ]
[ 1066-54-2 ]
[ 926009-63-4 ]

References: [1]Bioorganic and Medicinal Chemistry,2007,vol. 15,p. 1586 - 1605.
[2]Chinese Journal of Chemistry,2011,vol. 29,p. 1059 - 1062.

17
[ 624-28-2 ]
[ 124-40-3 ]
[ 26163-07-5 ]

Yield	Reaction Conditions	Operation in experiment
	In water;Reflux;	(A) 5-bromo-/V,/V-di methyl pyridi n-2-ami ne[095] A solution of 2,5-dibromopyridine (10 g, 42.3 mmol) in aqueousdimethylamine (50 mL) was refluxed overnight. The volatiles were removed in vacuo, and the residue was treated with EtOAc/PE. The precipitates were collected by filtration and dried to give the title compound. MS (m/z): 201 (M+H)+, 203 (M+H)+.
	In water;Reflux;	A solution of 2,5-dibromopyridine (10 g, 42.3 mmol) in aqueous dimethylamine (50 mL) was refluxed overnight. The volatiles were removed in vacuo, and the residue was treated with EtOAc/PE. The precipitates were collected by filtration and dried to give the title compound. MS (m/z): 201 (M+H)+, 203 (M+H)+.

References: [1]Bioorganic and Medicinal Chemistry,2007,vol. 15,p. 1586 - 1605.
[2]ACS Medicinal Chemistry Letters,2016,vol. 7,p. 374 - 378.
[3]Patent: WO2012/167423,2012,A1 .Location in patent: Page/Page column 36.
[4]Patent: US2014/121200,2014,A1 .Location in patent: Paragraph 0168; 0169.

18
[ 26163-07-5 ]
C₁₉H₁₆N₅Cl [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry,2007,vol. 15,p. 1586 - 1605.

19
[ 26163-07-5 ]
[ 754190-29-9 ]

References: [1]Bioorganic and Medicinal Chemistry,2007,vol. 15,p. 1586 - 1605.
[2]Chinese Journal of Chemistry,2011,vol. 29,p. 1059 - 1062.

20
[ 26163-07-5 ]
R 121920 [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 4787 - 4798.
[2]Advanced Synthesis and Catalysis,2003,vol. 345,p. 620 - 624.

21
[ 26163-07-5 ]
[ 1026876-69-6 ]

References: [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 4787 - 4798.

22
[ 26163-07-5 ]
[ 1026403-45-1 ]

References: [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 4787 - 4798.

23
[ 26163-07-5 ]
[ 764651-94-7 ]

References: [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 4787 - 4798.

24
[ 26163-07-5 ]
[ 764651-92-5 ]

References: [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 4787 - 4798.

25
[ 26163-07-5 ]
[ 764651-93-6 ]

References: [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 4787 - 4798.

26
[ 26163-07-5 ]
5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-N,N-dimethylpyridine-2-amine [ No CAS ]

References: [1]Advanced Synthesis and Catalysis,2003,vol. 345,p. 620 - 624.

27
[ 26163-07-5 ]
[ 680591-10-0 ]

Yield	Reaction Conditions	Operation in experiment
21%	With n-butyllithium; sulfur; In tetrahydrofuran; hexane; at -78℃; for 0.433333h;	[AT-78C] a solution of [(5-BROMO-PYRIDIN-2-YL)-DIMETHYL-AMINE] (15.0 mmol) in THF (50 mL) was added dropwise to a solution of n-BuLi in Hexane (1.6 [MOVL,] 10.0 mL). The reaction mixture was stirred for 15 min and sulfur (20.0 mmol) was added. After 1 min a solution of n-BuLi in Hexane (1.6 mol/L, 20.0 ml) was added. The reaction mixture was stirred for 10 min at-78C and purified immediately by flash-chromatography (ethyl acetate/heptane 1: 3) without previous work-up. A second flash-chromatography (gradient: ethyl [ACETATE/HEPTANE] 1: 19 to 1: 9) yielded 0.50 g (3.24 mmol, 21%) of 6-dimethylamino-pyridine-3-thiol as a yellow oil. LC-MS: rt = 0.46 min, 155 [(M+1,] ES+).

References: [1]Patent: WO2004/33418,2004,A2 .Location in patent: Page 34.

28
[ 1072-97-5 ]
[ 50-00-0 ]
[ 26163-07-5 ]

Yield	Reaction Conditions	Operation in experiment
43%		37 % Aqueous formaldehyde (13.55 ml, 180.3 mmol) was added dropwise to a solution of 2-amino-5-bromopyrydine (2.0 g, 11.56 mmol) in methanol (465 ml)at room temperature. To the mixture was added dropwise a solution of zinc chloride (3.94 g, 28.90 mmol) and sodium cyanoborohydride (3.63 g, 57.80 mmol) in methanol (155 ml)and the mixture was stirred at room temperature for 4 hrs. To the reaction mixture was added ice water (300 ml) at 5 C and then methanol was distilled off under reduced pressure. The residue was extracted with ethyl acetate - tetrahydrofuran (1/1) and the extract was washed with water and brine in turn and dried. The solvent was distilled off under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate = 24 and 5) to give 5-bromo-2-dimethylamino-pyridine (1.00 g, 43 %) as colorless crystals. m.p.: 39 - 41 C; IR (Nujol): 1588 cm-1; APCI-MS m/z: 201/203 [M+H]+.
43%	With sodium cyanoborohydride; zinc(II) chloride; In methanol; water; at 20℃; for 4h;	(Preparation 27) (0109) 1) 37% Aqueous formaldehyde (13.55 ml, 180.3 mmol) was added dropwise to a solution of 2-amino-5-bromopyrydine (2.0 g, 11.56 mmol) in methanol (465 ml)at room temperature. To the mixture was added dropwise a solution of zinc chloride (3.94 g, 28.90 mmol) and sodium cyanoborohydride (3. 63 g, 57.80 mmol) in methanol (155 ml) and the mixture was stirred at room temperature for 4 hrs. To the reaction mixture was added ice water (300 ml) at 5 C. and then methanol was distilled off under reduced pressure. The residue was extracted with ethyl acetate-tetrahydrofuran (1/1) and the extract was washed with water and brine in turn and dried. The solvent was distilled off under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate=24 and 5) to give 5-bromo-2-dimethylamino-pyridin- e (1.00 g, 43%) as colorless crystals. m.p.: 39-41 C.; IR (Nujol): 1588 cm-1; APCI-MS m/z: 201/203 [M+H]+.

References: [1]Patent: EP1481965,2004,A1 .Location in patent: Page 29.
[2]Patent: EP2959918,2015,A1 .Location in patent: Paragraph 0109.

Yield	Reaction Conditions	Operation in experiment
88%	With sodium hydride; In tetrahydrofuran; at 50℃;Reflux;	General procedure: To a solution of 5-bromo-2-aminopyri(mi)dine (1.0 mmol) in dry THF (2 mL) at 50C, NaH (2.2 mmol) was added slowly and the mixture was stirred until H2 evolution ceased. Alkylbromide (2.1 mmol) was then added and the reaction was refluxed overnight. The reaction was cooled, quenched with MeOH and extracted with Et20. Thecombined organics were washed with brine and dried over MgSO4. The oil obtained was passed through a plug of silica (Et20/hexanes) to obtain pure products.5-Bromo-N,N-dihexylpyridin-2-amine (8). Compound 8 was synthesized according to the general alkylation procedure listed above. 1-Bromohexane was used as thealkylbromide of choice. Yield: quantitative

30
[ 5683-33-0 ]
[ 37026-85-0 ]
[ 26163-07-5 ]

Yield	Reaction Conditions	Operation in experiment
72.0%	With sodium thiosulfate; In chloroform; water;	Example 191-1 Synthesis of 5-bromo-2-dimethylaminopyridine 2-Dimethylaminopyridine (1.0 ml) was dissolved in chloroform (60 ml). After adding tributylammonium bromide (3.88 g) thereto, the resultant mixture was stirred for 7 min. Then the reaction solution was washed with an aqueous solution of sodium thiosulfate and water, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate-methanol system) to give the title compound (1.097 g) as yellow crystals (yield: 72.0%). 1H-NMR (400 MHz, CDCl3): delta(ppm) 3.05(6H, s), 6.40(1H, dd, J=0.8, 8.8Hz), 7.48(1H, dd, J=2.8, 8.8Hz), 8.16(1H, dd, J=0.8, 2.8Hz).

References: [1]Patent: US2002/19531,2002,A1 .

31
[ 26163-07-5 ]
[ 20485-44-3 ]
[ 149805-92-5 ]

Yield	Reaction Conditions	Operation in experiment
89.6%	In diethyl ether; N,N-dimethyl-formamide;	Example 191-2 Synthesis of 2-dimethylamino-5-formylpyridine Tetramethylethylenediamine (8.0 ml) was added to the mixture of <strong>[26163-07-5]5-bromo-2-dimethylaminopyridine</strong> (5.0 g), N,N-dimethylformamide (6.1 ml) and diethyl ether employed as the solvent. The resultant mixture was treated in as in Example 93 to give the title compound (3.273 g) as pale yellow crystals (yield: 89.6%). 1H-NMR (400 MHz, CDCl3): delta(ppm) 3.21(6H, s), 6.56(1H, dd, J=0.4, 9.2Hz), 7.91(1H, dd, J=2.4, 9.2Hz), 8.55(1H, dd, J=0.4, 2.4Hz), 9.77(1H, s).

References: [1]Patent: US2002/19531,2002,A1 .

32
[ 624-28-2 ]
[ 26163-07-5 ]

Yield	Reaction Conditions	Operation in experiment
86%	With dimethyl amine; In tetrahydrofuran;	A. 5-Bromo-2-(dimethylamino)pyridine A solution of 2,5-dibromopyridine (11.84 g, 50.0 mmol) in 2.0 M solution of dimethylamine in tetrahydrofuran (100 mL) in a sealed tube was heated at 120 C. for 12 hours. The reaction was quenched with ethyl acetate and washed with water. The organic layer was dried over magnesium sulfate, filtered, and concentrated. The residue was then purified by chromatography (SiO2, 10-15% ethyl acetate/hexane) to provide the title compound (8.67 g, 86% yield): 1H NMR (CDCl3) 8.16 (d, 1H), 7.49 (dd, 1H), 6.41 (d, 1H), 3.05 (s, 6H); ES-MS m/z 201 [M+H]+.

References: [1]Patent: US6593322,2003,B1 .

33
[ 26163-07-5 ]
[ 813-19-4 ]
N,N-dimethyl-N-[5-(1,1,1-tributylstannyl)-2-pyridyl]amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%	tetrakis(triphenylphosphine)palladium (0); In toluene;	B. 2-(Dimethylamino)-5-(tributylstannyl)pyridine A mixture of 5-bromo-2-(dimethylamino)pyridine (0.71 g, 3.5 mmol), bis(tributyltin) (2.436 g, 4.2 mmol), and tetrakis(triphenylphosphine)palladium(0) (0.404 g, 0.35 mmol) in toluene (20 mL) was heated at 120 C. overnight. The reaction was concentrated and purified by chromatography (SiO2, 10% ethyl acetate/hexane) to provide the title compound (0.798 g, 55% yield): 1H NMR (CDCl3) 8.16 (dd, 1H), 7.49 (dd, 1H), 6.53 (dd, 1H), 3.07 (s, 6H), 1.28-1.70 (m, 18H), 0.85-0.95 (m, 9H); ES-MS m/z 411 [M+H]+.

References: [1]Patent: US6593322,2003,B1 .

34
[ 1072-97-5 ]
[ 74-88-4 ]
[ 84539-30-0 ]
[ 26163-07-5 ]

Yield	Reaction Conditions	Operation in experiment
34%	With NaH; In N,N-dimethyl-formamide; mineral oil;	a) 5-Bromo-2-(methylamino)pyridine and 5-bromo-2-(dimethylamino)pyridine To a suspension of NaH (60% dispersion in mineral oil, 0.44 g, 11 mmole) in dry DMF (40 mL) was added solid 2-amino-5-bromopyridine (1.73 g, 10 mmole) in portions over 5-10 min. Gas evolution was allowed to subside between additions. The resulting amber mixture was stirred for 15 min, then' methyl iodide (0.61 mL, 10 mmole) was added all at once. The reaction mixture was stirred at RT overnight, then was concentrated in vacuo. The residue was diluted with 5% NH4Cl (30 mL) and the mixture was extracted with CH2Cl2. The combined organic extracts were washed with brine, dried (MgSO4), and concentrated. Flash chromatography on silica gel (3% MeOH/CH2Cl2) separated the products. 5-Bromo-2-(methylamino)pyridine (0.60 g, 32 %) was obtained as a semisolid: TLC (3% MeOH/CH2Cl2) Rf 0.35; MS (ES) m/e 187 (M + H)+. 5-Bromo-2-(dimethylamino)pyridine (0.70 g, 34%) was obtained as a semisolid: TLC (3% MeOH/CH2Cl2) Rf 0.77; MS (ES) m/e 201 (M + H)+.

References: [1]Patent: EP1226138,2004,B1 .

35
[ 26163-07-5 ]
[ 111-34-2 ]
C₁₃H₂₀N₂O [ No CAS ]

References: [1]Synthesis,2008,p. 887 - 890.

36
[ 26163-07-5 ]
[ 4746-97-8 ]
[ 1228652-39-8 ]

References: [1]ACS Medicinal Chemistry Letters,2012,vol. 3,p. 1039 - 1044.

37
[ 26163-07-5 ]
[ 2942-13-4 ]
5-(6-methoxybenzo[d]thiazol-2-yl)-N,N-dimethylpyridin-2-amine [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 1976 - 1980.

38
[ 26163-07-5 ]
[ 4248-19-5 ]
[ 1242333-49-8 ]

References: [1]Tetrahedron Letters,2010,vol. 51,p. 4445 - 4448.

39
[ 26163-07-5 ]
[ 73183-34-3 ]
[ 1036991-24-8 ]

Yield	Reaction Conditions	Operation in experiment
76%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 100℃; for 12h;Inert atmosphere;	To a solution of 5-bromo-2-(NN-dimethylamino)pyridine (8.5 g, 42.3 mmol) and 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane) (12.9 g, 50.7 mmol) in dioxane (10 mL) was added KOAc (8.3 g, 84.6 mmol) and Pd(dppf)Cl2 (1.55 g, 2.1 mmol) at 25 C under N2. The mixture was heated to 100 C and stirred at this temperature for 12 hours. LCMS showed that the reaction was complete. The mixture was filtered and concentrated under reduced pressure to give a residue which was purified by silica gel column chromatography (petroleum ether / ethyl acetate=50/1 to 3/1) to give 2-(2-(N,N-dimethylamino)pyrid-5-yl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (8 g, 32.2 mmol, 76% yield) as a yellow solid 1H NMR 400 MHz CDCl3 = 8.53 (s, 1H), 7.75-7.78 (d, 1H), 6.43-6.45 (d, 1H), 3.09 (s, 6H), 1.22-1.30 (m, 12H). ESI-MS (m/z): 249.2 (M+H)+
	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 20℃;Inert atmosphere;	PdCI2(dppf)-CH2Cl2 adduct (81 mg, 0.099 mmol) was added to a solution of 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1 ,3,2-dioxaborolane) (379 mg, 1 .492 mmol), 5-bromo- N,N-dimethylpyridin-2-amine (200 mg, 0.995 mmol) and potassium acetate (293 mg, 2.98 mmol) in 1 ,4-dioxane (40 mL) at room temperature under an atmosphere of nitrogen. The resulting solution was stirred at 100 C for 12 hr. The system was filtered and the filtrate was concentrated to afford crude product.which was used for the next step. LCMS: [M+H] 249.1 .

References: [1]Patent: WO2017/120429,2017,A1 .Location in patent: Page/Page column 262.
[2]Advanced Synthesis and Catalysis,2010,vol. 352,p. 2002 - 2010.
[3]European Journal of Organic Chemistry,2012,p. 595 - 603.
[4]Patent: WO2017/98440,2017,A1 .Location in patent: Page/Page column 248.
[5]Patent: WO2019/201283,2019,A1 .Location in patent: Page/Page column 380; 381.

40
[ 26163-07-5 ]
[ 1015484-22-6 ]
[ 1245644-05-6 ]

References: [1]Synlett,2011,p. 349 - 356.

41
[ 1072-97-5 ]
[ 74-88-4 ]
[ 26163-07-5 ]

Yield	Reaction Conditions	Operation in experiment
94%		Step 64a: 5-Bromo-N,N-dimethylpyridin-2-amine (cCompound 0601-114)To a solution of 5-bromopyridin-2-amine (1.0 g, 5.8 mmol) in THF (25 mL) was added NaH (0.92 g, 23.1 mmol) at 0 C and stirred for 10 min. followed by the addition of CH3I (1 mL, 16 mmol) and stirred fori h. Water (30 mL) was added and extracted with ethyl acetate (3 x 30 mL). The combined organic layers were washed with brine, dried over Na2S04, concentrated and purified by column chromatography on silica gel (ethyl acetate in petroleum ether, 10% v/v) to give the title compound (1.1 g, 94%) as a white solid LCMS: 203 [M+2]+; 1HNMR (400 MHz, DMSO-<¾) delta 2.99 (s, 6H), 6.61 (d, J= 9.6 Hz, 1H), 7.62 (dd, J= 9.2, 2.8 Hz, 1H), 8.12 (d, J= 2.4 Hz, 1H).
94%		Step 64a: 5-Bromo-N,N-dimethylpyridin-2-amine (compound 0601-114)[0486]To a solution of 5-bromopyridin-2-amine (1.0 g, 5.8 mmol) in THF (25 mL) was added NaH (0.92 g, 23.1 mmol) at 0 C. and stirred for 10 min. followed by the addition of CH3I (1 mL, 16 mmol) and stirred for 1 h. Water (30 mL) was added and extracted with ethyl acetate (3×30 mL). The combined organic layers were washed with brine, dried over Na2SO4, concentrated and purified by column chromatography on silica gel (ethyl acetate in petroleum ether, 10% v/v) to give the title compound (1.1 g, 94%) as a white solid LCMS: 203 [M+2]+; 1HNMR (400 MHz, DMSO-d6) delta 2.99 (s, 6H), 6.61 (d, J=9.6 Hz, 1H), 7.62 (dd, J=9.2, 2.8 Hz, 1H), 8.12 (d, J=2.4 Hz, 1H).
94%		THF (25mL) in 5-bromo-2-amine (1.0g, 5.8mmol) to a solution of NaH (0.92g, 23.1mmol) was stirred addition to 10 minutes at 0 , then CH3I (1mL, 16mmol) and the mixture was stirred for 1 hour with the addition of. With the addition of water (30mL) and extracted with ethyl acetate (3x30mL). The combined organic layers were washed with brine, dried over Na2SO4, and concentrated and purified by column chromatography (petroleum ether in ethyl acetate, 10% v / v) on silica gel to give the white solid title compound obtained as (1.1g, 94%).

References: [1]Patent: WO2011/130628,2011,A1 .Location in patent: Page/Page column 206.
[2]Patent: US2013/102595,2013,A1 .Location in patent: Paragraph 0485; 0486.
[3]Patent: JP2015/187145,2015,A .Location in patent: Paragraph 0418.
[4]European Journal of Organic Chemistry,2020.
[5]Organic and Biomolecular Chemistry,2019,vol. 17,p. 1749 - 1753.

42
[ 26163-07-5 ]
[ 411235-57-9 ]
[ 1245645-43-5 ]

Yield	Reaction Conditions	Operation in experiment
80%	With potassium phosphate tribasic heptahydrate; C45H53ClFeNO2PPd; In water; toluene; at 100℃; for 6h;Inert atmosphere;	General procedure: Potassium phosphate (0.75 mmol) and IIe (1 mol %) was added to the solution of aryl halides (0.25 mmol) and cyclopropylboronic acid (0.5 mmol) in toluene (2.0 mL) and water (100 muL). The mixture was heated to 100 C for a proper time under nitrogen atmosphere and cooled to room temperature. Water (10 mL) was added and the mixture was extracted with EtOAc (3×15 mL), evaporated and purified by chromatography on silica gel.

References: [1]Tetrahedron,2012,vol. 68,p. 900 - 905.

43
[ 26163-07-5 ]
[ 1374328-49-0 ]

References: [1]European Journal of Organic Chemistry,2012,p. 595 - 603.

44
[ 26163-07-5 ]
[ 24388-23-6 ]
[ 1374328-49-0 ]

References: [1]European Journal of Organic Chemistry,2012,p. 595 - 603.

45
[ 26163-07-5 ]
[ 329214-79-1 ]
[ 882864-93-9 ]

References: [1]European Journal of Organic Chemistry,2012,p. 595 - 603.

46
[ 26163-07-5 ]
benzyl methyl(piperidin-4-yl)carbamate [ No CAS ]
[ 1365156-60-0 ]

Yield	Reaction Conditions	Operation in experiment
67%	With potassium tert-butylate;tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In toluene; at 80℃; for 16h;Inert atmosphere;	Stage 1: Benzyl 1-(6-(dimethylamino)pyridin-3-yl)piperidin-4-yl(methyl)carbamate Benzyl methyl(piperidin-4-yl)carbamate (stage 3 AMN-52) (616 mg, 2.4875 mmol, 1.0 eq.), <strong>[26163-07-5]5-bromo-2-dimethylaminopyridine</strong> (500 mg, 2.4875 mmol, 1.0 eq.) and KOBut (557 mg, 4.978 mmol, 2.0 eq.) were taken up in toluene (15 ml) and degassed with N2. BI NAP (77 mg, 0.124 mmol, 0.05 eq.) and Pd2(dba)3 (113 mg, 0.124 mmol, 0.05 eq.) were then added and the mixture was heated for 16 hours at 80 C. After monitoring by TLC, the reaction mixture was filtered over Celite and the filtrate was concentrated under reduced pressure and purified by column chromatography (silica gel, 2% MeOH in DCM). Yield: 67% (500 mg, 1.358 mmol)

References: [1]Patent: US2012/71461,2012,A1 .Location in patent: Page/Page column 142.

47
[ 26163-07-5 ]
C₁₅H₂₃N₆ [ No CAS ]