1060812-84-1|5-Bromopyrazolo[1,5-a]pyridine| Ambeed

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Quality Control of [ 1060812-84-1 ] Purity: 97% SDS Specification

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Product Details of [ 1060812-84-1 ]

CAS No. :	1060812-84-1
Formula :	C₇H₅BrN₂
M.W :	197.03
SMILES Code :	BrC1=CC2=CC=NN2C=C1
MDL No. :	MFCD13189494
InChI Key :	WQOAKXFBWOXJNG-UHFFFAOYSA-N
Pubchem ID :	68503138

Safety of [ 1060812-84-1 ]

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

Computational Chemistry of [ 1060812-84-1 ] Show Less

Physicochemical Properties

Num. heavy atoms	10
Num. arom. heavy atoms	9
Fraction Csp3	0.0
Num. rotatable bonds	0
Num. H-bond acceptors	1.0
Num. H-bond donors	0.0
Molar Refractivity	42.89
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	17.3 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.0
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	1.75
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.1
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	2.15
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	1.67
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.93

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.83
Solubility	0.291 mg/ml ; 0.00148 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.	-1.73
Solubility	3.66 mg/ml ; 0.0186 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	-2.94
Solubility	0.225 mg/ml ; 0.00114 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.	-6.26 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	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)	1.54

Application In Synthesis of [ 1060812-84-1 ]

* 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 [ 1060812-84-1 ]

[ 1060812-84-1 ] Synthesis Path-Downstream 1~35

2
[ 1101120-33-5 ]
[ 1060812-84-1 ]

References: [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 69 - 85.

3
[ 1060812-84-1 ]
C₁₃H₁₄N₂OSi [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 69 - 85.

4
[ 1060812-84-1 ]
C₉H₉BrN₄ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 69 - 85.

5
[ 1060812-84-1 ]
C₁₂H₁₄N₄ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 69 - 85.

6
[ 1060812-84-1 ]
C₁₁H₁₂N₄ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 69 - 85.

7
[ 1060812-84-1 ]
C₁₁H₁₀N₄ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 69 - 85.

8
[ 1060812-84-1 ]
[ 1101120-63-1 ]

References: [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 69 - 85.

9
[ 1060812-84-1 ]
[ 1101120-61-9 ]

References: [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 69 - 85.

10
[ 1060812-84-1 ]
[ 1101120-65-3 ]

References: [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 69 - 85.

11
[ 1060812-84-1 ]
[ 1101118-18-6 ]

References: [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 69 - 85.

12
[ 1060812-84-1 ]
[ 1101118-21-1 ]

References: [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 69 - 85.

13
[ 1060812-84-1 ]
[ 1101118-20-0 ]

References: [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 69 - 85.

14
[ 1060812-84-1 ]
[ 1101118-22-2 ]

References: [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 69 - 85.

15
[ 1060812-84-1 ]
[ 68-12-2 ]
[ 1101120-53-9 ]

Yield	Reaction Conditions	Operation in experiment
96%		General procedure: These were made by decarboxylation/Vilsmeier or hydrolysis/reduction/reoxidation as detailed below, unless otherwise stated.Decarboxylation was carried out by refluxing a solution of the ester (1 equiv) in 40percent aqueous H2SO4 (3 mL) for 18 h. The solution was then cooled in ice and neutralised to pH 7 with 6 M NaOH, then extracted twice with CH2Cl2. The combined extracts were dried (Na2SO4) and the solvent removed in vacuo to leave the decarboxylated material. The pyrazolo[1,5-a]pyridine was then reacted under Vilsmeier conditions in dry DMF (2 mL) with POCl3 (3 equiv) at 0 °C under an atmosphere of N2. The reaction mixture was then warmed to room temperature and stirred for 2 h. The solution was poured onto ice, basified to pH 10 with 1 M NaOH, stirred for 1 h then extracted twice with CH2Cl2. The combined extracts were washed twice with water, dried (Na2SO4) and the solvent removed in vacuo to leave the aldehyde.Alternatively, the ester was hydrolysed by refluxing a solution of the ester (1 equiv) in 1 M NaOH (3 equiv) and EtOH (5 mL) for 6 h. The EtOH was removed in vacuo, and then the aqueous residue acidified to pH 1 with 1 M HCl. The precipitated carboxylic acid was filtered off, washed with water and dried. The carboxylic acid was reduced by adding CDI (1.5 equiv) to a suspension of carboxylic acid (1 equiv) in dry THF (10 mL) under an atmosphere of N2. After stirring for 18 h, the resulting solution was added dropwise to a solution of NaBH4 (5 equiv) in H2O (10 mL) and stirred for 30 min. The reaction was then quenched by the addition of 1 M HCl and stirred for a further 30 min. The solution was neutralised with saturated aqueous NaHCO3 and extracted twice with CH2Cl2. The combined organic layers were dried (Na2SO4) and the solvent removed in vacuo. Chromatography (eluting with a hexanes: EtOAc gradient) gave the alcohol. Reoxidation was carried out by stirring a suspension of the pyrazolo[1,5-a]pyridine-3-methanol (1 equiv) and MnO2 (10 equiv) in CH2Cl2 (2 mL) at room temperature for 4 days. The reaction mixture was then filtered through celite, washed with CH2Cl2, and the solvent removed from the filtrate in vacuo to leave the aldehyde.

References: [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 69 - 85.

16
ethyl 5-aminopyrazolo[1,5-a]pyridine-3-carboxylate trifluoroacetate [ No CAS ]
[ 1060812-84-1 ]

References: [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 69 - 85.

17
[ 885276-93-7 ]
[ 1060812-84-1 ]

Yield	Reaction Conditions	Operation in experiment
99.5%	With sulfuric acid; at 100℃; for 4.0h;	A solution of ethyl 5-bromopyrazolo[1,5-a]pyridine-3-carboxylate (240 mg, 0.89 mmol) in 40percent H2SO4 (12 mL) was stirred at 100° C. for 4 hours, then cooled to rt, and neutralized to pH=7 with aq. NaOH (6 M) in ice bath. The resulted mixture was extracted with DCM (25 mL×2). The combined organic phases were dried over anhydrous Na2SO4 and concentrated in vacuo to give the title compound as a light yellow solid (175 mg, 99.5percent). MS (ESI, pos. ion) m/z: 196.9 [M+H]+.
96%		General procedure: These were made by decarboxylation/Vilsmeier or hydrolysis/reduction/reoxidation as detailed below, unless otherwise stated.Decarboxylation was carried out by refluxing a solution of the ester (1 equiv) in 40percent aqueous H2SO4 (3 mL) for 18 h. The solution was then cooled in ice and neutralised to pH 7 with 6 M NaOH, then extracted twice with CH2Cl2. The combined extracts were dried (Na2SO4) and the solvent removed in vacuo to leave the decarboxylated material. The pyrazolo[1,5-a]pyridine was then reacted under Vilsmeier conditions in dry DMF (2 mL) with POCl3 (3 equiv) at 0 °C under an atmosphere of N2. The reaction mixture was then warmed to room temperature and stirred for 2 h. The solution was poured onto ice, basified to pH 10 with 1 M NaOH, stirred for 1 h then extracted twice with CH2Cl2. The combined extracts were washed twice with water, dried (Na2SO4) and the solvent removed in vacuo to leave the aldehyde.Alternatively, the ester was hydrolysed by refluxing a solution of the ester (1 equiv) in 1 M NaOH (3 equiv) and EtOH (5 mL) for 6 h. The EtOH was removed in vacuo, and then the aqueous residue acidified to pH 1 with 1 M HCl. The precipitated carboxylic acid was filtered off, washed with water and dried. The carboxylic acid was reduced by adding CDI (1.5 equiv) to a suspension of carboxylic acid (1 equiv) in dry THF (10 mL) under an atmosphere of N2. After stirring for 18 h, the resulting solution was added dropwise to a solution of NaBH4 (5 equiv) in H2O (10 mL) and stirred for 30 min. The reaction was then quenched by the addition of 1 M HCl and stirred for a further 30 min. The solution was neutralised with saturated aqueous NaHCO3 and extracted twice with CH2Cl2. The combined organic layers were dried (Na2SO4) and the solvent removed in vacuo. Chromatography (eluting with a hexanes: EtOAc gradient) gave the alcohol. Reoxidation was carried out by stirring a suspension of the pyrazolo[1,5-a]pyridine-3-methanol (1 equiv) and MnO2 (10 equiv) in CH2Cl2 (2 mL) at room temperature for 4 days. The reaction mixture was then filtered through celite, washed with CH2Cl2, and the solvent removed from the filtrate in vacuo to leave the aldehyde.
60%	With sulfuric acid; In water; at 110℃; for 16.0h;	A suspension of ethyl 5-bromopyrazolo[1 ,5-a]pyridine-3-carboxylate 94-1 (1 .6 g, 5.94 mmol) in 70percent aq. H2S04 (15 mL) was maintained at 110 00 for 16 h. The reaction mixture was cooled to room temperature and poured into ice-cold water. The pH was adjusted to 7.0 using aq. 1 N NaOH solution, filtered the precipitated solid, washed with water, pet- ether and dried under vacuum to afford 700 mg (60percent) of 5-bromopyrazolo[1,5-a]pyridine 94-2 as an off white solid. ESI-LC/MS: m/z 196.74 (M+H) & 198.71 & [(M+2)+H]; R = 2.39 mm [Waters Acquity UPLC with Quattro-micro detector; Waters Acquity BEH 018, 1 .7 pm, 2.1 X 50mm column; gradient of 90:10 H20 (0.025percent TEA): CH3CN (0.025percent TEA) hold for 0.5 mm and to 10:90 H20 (0.025percent TEA) :CH3CN (0.025percent TEA) in 3.5 mm and hold for 1.5 mm with flow rate of 0.4 mL/min].

55%	With sulfuric acid; at 80℃;	Compound 64.4. 5-BromopyrazoIo[l,5-a] pyridine. Into a 50-mL round-bottom flask, was placed ethyl 5-bromopyrazolo[l ,5-a]pyridine-3-carboxylate (compound 64.3, 100 mg, 0.37 mmol). Sulfuric acid (50percent, 4 mL) was added carefully in portions at room temperature, then the resulting solution was stirred overnight at 80 °C. After cooling to room temperature, the pH of the solution was carefully adjusted to 8-9 with aqueous sodium hydroxide (5 M) and then extracted with ethyl acetate (2 x 20 mL). The combined organic extracts were washed with brine (20 mL), dried (Na2S04), filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography with ethyl acetate/petroleum ether (1 : 10) as the eluent to yield the title compound as a brown solid (40 mg, 55
55%	With sulfuric acid; at 80℃;	Compound 64.4. 5-Bromopyrazolo[l,5-]pyridine. Into a 50-mL round-bottom flask, was placed ethyl 5-bromopyrazolo[l,5-a]pyridine-3-carboxylate (compound 64.3, 100 mg, 0.37 mmol). Sulfuric acid (50percent, 4 mL) was added carefully in portions at room temperature, then the resulting solution was stirred overnight at 80 °C. After cooling to room temperature, the pH of the solution was carefully adjusted to 8-9 with aqueous sodium hydroxide (5 M) and then extracted with ethyl acetate (2 x 20 mL). The combined organic extracts were washed with brine (20 mL), dried (Na2S04), filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography with ethyl acetate/petroleum ether (1 : 10) as the eluent to yield the title compound as a brown solid (40 mg, 55 percent)
550 mg	With sulfuric acid; at 120℃; for 3.0h;	A colorless mixture of A-13 (900.0 mg, 3.34 mmol) in H2504 (50percent,10.0 mL) was stirred at 120 °C for 3 hours. The mixture was diluted with ice-water, neutralizedwith solid Na2CO3 to pH = 7, and extracted with DCM (50 mL x 2). The combined organiclayers were washed with brine (10 mL), dried over Na2504, filtered and concentrated to affordA-14 (550.00 mg, 2.79 mmol) as an oil. ?H NMR (400 MHz, CDC13) oe11 8.38 - 8.32 (m, 1H),7.95 (d, 1H), 7.72 (d, 1H), 6.83 (dd, 1H), 6.47 (d, 1H).

References: [1]Patent: US2014/234254,2014,A1 .Location in patent: Paragraph 0329; 0330; 0341; 0342.
[2]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 69 - 85.
[3]Patent: WO2014/78802,2014,A1 .Location in patent: Page/Page column 158.
[4]Patent: WO2014/8197,2014,A1 .Location in patent: Page/Page column 136.
[5]Patent: WO2015/95767,2015,A1 .Location in patent: Page/Page column 151.
[6]Patent: WO2018/98500,2018,A1 .Location in patent: Page/Page column 88; 89.

18
[ 98400-69-2 ]
[ 1060812-84-1 ]

References: [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 69 - 85.

19
[ 1533440-88-8 ]
[ 1060812-84-1 ]

References: [1]Patent: WO2014/8197,2014,A1 .
[2]Patent: WO2015/95767,2015,A1 .

20
[ 1060812-84-1 ]
[ 1352881-82-3 ]

Yield	Reaction Conditions	Operation in experiment
97.5%	With N-iodo-succinimide; In methanol; at -10 - 20℃; for 18.5h;	To a solution of <strong>[1060812-84-1]5-bromopyrazolo[1,5-a]pyridine</strong> (900 mg, 4.46 mmol) in methanol (100 mL) was added N-iodosuccinimide (1 g, 4.46 mmol) slowly at -10 C. The mixture was stirred at -10 C. for 0.5 hour, then warmed to rt and stirred further for 18 hours. The mixture was concentrated in vacuo, and the residue was dissolved in DCM (200 mL). The resulted mixture was washed with a saturated Na2S2O3 aqueous solution (200 mL). The separated organic phase was concentrated in vacuo to give the title compound as a light pink solid (1.4 g, 97.5%). MS (ESI, pos. ion) m/z: 322.8 [M+H]+.

References: [1]Patent: US2014/234254,2014,A1 .Location in patent: Paragraph 0343; 0344.
[2]Journal of Medicinal Chemistry,2018,vol. 61,p. 4386 - 4396.
[3]MedChemComm,2014,vol. 5,p. 41 - 46.

21
[ 1060812-84-1 ]
5-bromo-3-(3-(2-methyl-5-nitrophenylsulfonyl)prop-1-enyl)pyrazolo[1,5-a]pyridine [ No CAS ]

References: [1]MedChemComm,2014,vol. 5,p. 41 - 46.

22
[ 1060812-84-1 ]
1-(5-bromopyrazolo[1,5-a]pyridin-3-yl)-3-(2-methyl-5-nitrophenylsulfonyl)propan-1-ol [ No CAS ]

References: [1]MedChemComm,2014,vol. 5,p. 41 - 46.

23
[ 1060812-84-1 ]
[ 1610612-40-2 ]

References: [1]Patent: WO2014/78802,2014,A1 .

24
[ 1060812-84-1 ]
[ 1610612-33-3 ]

References: [1]Patent: WO2014/78802,2014,A1 .

25
[ 1060812-84-1 ]
[ 1610611-09-0 ]

References: [1]Patent: WO2014/78802,2014,A1 .

26
[ 1060812-84-1 ]
[ 765-30-0 ]
[ 1610612-76-4 ]

Yield	Reaction Conditions	Operation in experiment
62%	With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate; In toluene; at 90℃; for 2.0h;Inert atmosphere; Microwave irradiation;	A solution mixture of 5-bromopyrazolo[1 ,5-a]pyridine 94-2 (900 mg, 4.59 mmol) and tBuONa (661 .2 mg, 6.88 mmol) in toluene (10 mL) was degassed with argon for about 10 mm. To this mixture were added Pd2(dba)3 (84 mg, 0.091 mmol), BINAP (114.2 mg, 0.lO2mmol) and cyclopropylamine (2 mL, 28.87 mmol) under argon atmosphere. The resulting reaction mixture was maintained at 90°C for 2 h under microwave irradiation. The reaction mixture was diluted with water (30 mL) and extracted with ethyl acetate (2 x 50 mL). The combined organic layer was washed with water (30 mL), brine (25 mL), dried over anhydrous Na2SO4 and concentrated. The crude product was purified by column chromatography over silica-gel (100-200 mesh) using a solvent gradient of 25percent ethyl acetate in pet-ether to afford 500 mg (62percent) of N-cyclopropylpyrazolo[1,5-a]pyridin-5- amine 147-1 as a brown solid. 1H-NMR (400 MHz, CDCI3): c58.18 (d, J= 7.5 Hz, 1H), 7.78 (d, J= 2.2 Hz, 1H), 6.72 (d, J= 2.6 Hz, 1H), 6.15-6.18 (m, 2H), 4.28 (5, 1H), 2.44-2.49 (m, 1 H), 0.78-0.80 (m, 2H), 0.54-0.58 (m, 1 H). ESI-LC/MS: m/z 173.75 (M+H); R =1 .99 mm [Waters Acquity UPLC with Quattro-micro detector; Waters Acquity BEH Cl 8,1.7 pm, 2.1 X 50 mm column; gradient of 90:10 H20 (0.025percent TEA): CH3CN (0.025percent TEA) hold for 0.5 mm and to 10:90 H20 (0.025percent TEA):CH3CN (0.025percent TEA) in 3.5 mm and hold for 1 .5 mm with flow rate of 0.4 mLlmin].

References: [1]Patent: WO2014/78802,2014,A1 .Location in patent: Page/Page column 231; 232.

27
[ 1060812-84-1 ]
[ 74-89-5 ]
[ 1610612-39-9 ]

Yield	Reaction Conditions	Operation in experiment
	With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate; In tetrahydrofuran; toluene; at 100℃; for 4.0h;Inert atmosphere; Microwave irradiation;	A solution mixture of 5-bromopyrazolo[1 ,5-a]pyridine 94-2 (500 mg, 2.537 mmol) and tBuONa (367 mg, 3.822 mmol) in toluene (10 mL) was degassed with argon for about 10 mm. To this mixture were added Pd2(dba)3 (46.7 mg, 0.051 mmol), BINAP (63.4 mg, 0.102 mmol) and 2.0 M methylamine in THE (2 mL, 4.081 mmol) under argon atmosphere. The resulting reaction mixture was maintained atlOO°Ofor4 h under microwave irradiation. The reaction mixture was diluted with water (30 mL) and extracted with ethyl acetate (2 x 50 mL). The combined organic layer was washed with water (20 mL), brine (20 mL), dried over anhydrous Na2SO4 and concentrated. The residue was passed through a column silica-gel (100-200 mesh) using a solvent gradient of 25percent ethyl acetate in pet-ether to afford 110 mg (crude) of N-methylpyrazolo[1,5-a]pyridin-5-amine 94-3 as an off white solid. The crude product was used as such for next step without further purification. ESI-LC/MS: m/z 147.48 (M+H); R. = 1.53 mm [Waters Acquity UPLO with Quattro-micro detector; Waters Acquity BEH 018, 1 .7 pm, 2.1 X 50 mm column; gradient of 90:10 H20 (0.025percent TEA): CH3CN (0.025percent TEA) hold for 0.5 mm and to 10:90 H20 (0.025percent TFA):CH3CN (0.025percent TEA) in 3.5 mm and hold for 1 .5 mm with flow rate of 0.4 mL/min].

References: [1]Patent: WO2014/78802,2014,A1 .Location in patent: Page/Page column 158; 159.

28
[ 1120-87-2 ]
[ 1060812-84-1 ]

References: [1]Patent: WO2014/78802,2014,A1 .

29
[ 1060812-84-1 ]
[ 1083326-73-1 ]
[ 1621718-79-3 ]

Yield	Reaction Conditions	Operation in experiment
73%	With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In 1,4-dioxane; water; at 90℃;Inert atmosphere;	mixture of <strong>[1060812-84-1]5-bromopyrazolo[1,5-a]pyridine</strong> (197 mg, 1 mmol), 2,4-difluoro-N-(2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)benzene sulfonamide (639 mg, 1.5 mmol), Na2CO3 (318 mg, 3.0 mmol) and Pd(PPh3)2Cl2 (35 mg, 0.05 mmol) in 1,4-dioxane/H2O (5 mL/1 mL) was stirred at 90° C. under nitrogen atmosphere, and the reaction was monitored by TLC. After completion, the reaction mixture was cooled to room temperature and extracted with diethyl ether (10 mL). The organic phase was washed with brine (10 mL×2), dried with anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (v/v)=30/1) to give the title compound as a white solid (303 mg, 73percent). MS (ESI, pos. ion) m/z: 416.9 [M+H]+.

References: [1]Patent: US2014/234254,2014,A1 .Location in patent: Paragraph 0369; 0370.

30
[ 1060812-84-1 ]
[ 3724-43-4 ]
[ 1101120-53-9 ]

Yield	Reaction Conditions	Operation in experiment
100%	In dichloromethane; at 44℃;	To a solution of <strong>[1060812-84-1]5-bromopyrazolo[1,5-a]pyridine</strong> (175 mg, 0.89 mmol) in DCM (6 mL) was added (chloromethylene)dimethyliminium chloride (632 mg, 3.56 mmol). The reaction was stirred at 44° C. overnight, and concentrated in vacuo. The residue was dissolved in saturated NaHCO3 aqueous solution (25 mL) and the resulted mixture was then extracted with EtOAc (25 mL×3). The combined organic phases were dried over anhydrous Na2SO4 and concentrated in vacuo to give the title compound as a light yellow solid (225 mg, 100percent). [0332] MS (ESI, pos. ion) m/z: 225.0 [M+H]+.

References: [1]Patent: US2014/234254,2014,A1 .Location in patent: Paragraph 0331; 0332.

31
[ 1060812-84-1 ]
[ 1621718-72-6 ]

References: [1]Patent: US2014/234254,2014,A1 .

32
[ 1060812-84-1 ]
[ 1621718-41-9 ]

References: [1]Patent: US2014/234254,2014,A1 .

33
[ 1060812-84-1 ]
[ 1621718-75-9 ]

References: [1]Patent: US2014/234254,2014,A1 .

34
[ 1060812-84-1 ]
[ 1352900-95-8 ]

References: [1]Patent: US2014/234254,2014,A1 .

35
[ 1060812-84-1 ]
[ 1621718-37-3 ]

References: [1]Patent: US2014/234254,2014,A1 .

Historical Records

Technical Information

• Alkyl Halide Occurrence • General Reactivity • Grignard Reaction • Hiyama Cross-Coupling Reaction • Kinetics of Alkyl Halides • Kumada Cross-Coupling Reaction • Preparation of Amines • Reactions of Alkyl Halides with Reducing Metals • Reactions of Amines • Reactions of Dihalides • Stille Coupling • Substitution and Elimination Reactions of Alkyl Halides • Suzuki Coupling

Related Functional Groups of
[ 1060812-84-1 ]

Bromides

A449153 [294877-29-5]

1-(3-Bromophenyl)-3,5-dimethyl-1H-pyrazole

Similarity: 0.88

A166578 [1264193-11-4]

6-Bromopyrazolo[1,5-a]pyridine

Similarity: 0.87

A235054 [5910-12-3]

3-Bromopyrazolo[1,5-a]pyridine

Similarity: 0.85

A267315 [590417-94-0]

6-Bromo-1-methyl-1H-indazole

Similarity: 0.83

A115314 [465529-57-1]

5-Bromo-1-methyl-1H-indazole

Similarity: 0.82

Related Parent Nucleus of
[ 1060812-84-1 ]

Other Aromatic Heterocycles

A166578 [1264193-11-4]

6-Bromopyrazolo[1,5-a]pyridine

Similarity: 0.87

A235054 [5910-12-3]

3-Bromopyrazolo[1,5-a]pyridine

Similarity: 0.85

A281579 [1101120-37-9]

Pyrazolo[1,5-a]pyridin-5-amine

Similarity: 0.83

A221861 [1345121-23-4]

6-Bromo-5-methylpyrazolo[1,5-a]pyridine

Similarity: 0.79

A100727 [1207839-86-8]

4-Bromo-6-methoxypyrazolo[1,5-a]pyridine

Similarity: 0.73

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CAS No.: 1060812-84-1

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