1210838-82-6|5-Bromo-3-ethynylpyridin-2-ylamine| Ambeed

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Quality Control of [ 1210838-82-6 ] Purity: 97% SDS Specification

COA

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NMR

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CNMR

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HPLC

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Product Details of [ 1210838-82-6 ]

CAS No. :	1210838-82-6
Formula :	C₇H₅BrN₂
M.W :	197.03
SMILES Code :	BrC1=CN=C(C(=C1)C#C)N
MDL No. :	MFCD10566045
InChI Key :	MKIMFNOYJFCQRQ-UHFFFAOYSA-N
Pubchem ID :	45789786

Safety of [ 1210838-82-6 ]

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

Computational Chemistry of [ 1210838-82-6 ] Show Less

Physicochemical Properties

Num. heavy atoms	10
Num. arom. heavy atoms	6
Fraction Csp3	0.0
Num. rotatable bonds	0
Num. H-bond acceptors	1.0
Num. H-bond donors	1.0
Molar Refractivity	44.28
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	38.91 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.92
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	1.44
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	1.5
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.	1.56
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	1.9
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.66

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.41
Solubility	0.762 mg/ml ; 0.00387 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.	-1.86
Solubility	2.7 mg/ml ; 0.0137 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	-2.6
Solubility	0.489 mg/ml ; 0.00248 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	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.	-6.48 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	1.0 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)	2.01

Application In Synthesis of [ 1210838-82-6 ]

* 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 [ 1210838-82-6 ]

[ 1210838-82-6 ] Synthesis Path-Downstream 1~35

1
[ 1262985-25-0 ]
[ 1210838-82-6 ]

Yield	Reaction Conditions	Operation in experiment
	With lithium hydroxide; In 1-methyl-pyrrolidin-2-one; water; at 60 - 75℃; under 37.5038 - 75.0075 Torr;	Example 7; a) Preparation of 5-bromo-7-azaindole (3 or Ia) from isolated 2-amino-5-bromo-3-iodopyridine; A suspension of 2-amino-5-bromo-3-iodopyridine (5.0 g, 16.7 mmol), bis-(triphenylphosphine)-palladium(II)-dichloride (43 mg, 0.061 mmol), copper(I)iodide (29.4 mg, 0.15 mmol) and triethylamine (2.21 g, 21.8 mmol) in dichloromethane (20 mL) was treated at 23 to 30 C. within 1 to 2 hours with a solution of 1,1-dimethyl-2-propyn-1-ol (1.85 g, 21.7 mmol) in dichloromethane (10 mL) and the resulting mixture was stirred at 25 C. for 4 hours. The mixture was diluted with dichloromethane (10 mL) and washed with water (2×25 mL). The organic phase was then treated with 1 M HCl (40 mL). The layers were separated and the organic layer was extracted with 1 M HCl (15 mL). The combined product containing aqueous layers were washed with dichloromethane (2×8 mL). The pH of the aqueous layer was adjusted to pH 7-9 by the drop wise addition of sodium hydroxide solution (28% in water). The resulting suspension was stirred at 20 C. over night and the crystals were then filtered off and washed with water (2×5 mL). The wet crystals were dissolved in N-methylpyrrolidone (50 mL) and treated within 2 hours at 60 C. and 50-100 mbar with an aqueous solution of lithium hydroxide (2.4 M, 32 mL). The resulting mixture was heated to 75 C. and stirred at this temperature and under reduced pressure (50-100 mbar) for 15-20 hours. Toluene (20 mL) and water (20 mL) were then added and the layers were separated. The aqueous layer was extracted with toluene (3×25 mL). The combined organic layers were washed with water (3×10 mL) and then concentrated to dryness. The residue was dissolved in N-methylpyrrolidone (50 mL) and treated at 60 C. with potassium tert.-butylate (3.52 g, 30.7 mmol). After stirring for 3 hours at 60 C., the mixture was cooled to ambient temperature and diluted with toluene (40 mL) and water (40 mL). The aqueous layer was separated and back extracted with toluene (3×50 mL). The combined toluene layers were washed with water (3×10 mL) and then concentrated to dryness. The residue was dissolved in a hot mixture of toluene and n-heptane (20 mL). The clear solution was cooled to -5 C. within 4 to 6 hours whereupon crystals precipitated. The suspension was stirred at -5 C. for 2-4 hours. The crystals were filtered off, washed with heptane and dried at 45 C./<30 mbars over night to afford 5-bromo-7-azaindole (2.05 g, 62% yield) as slightly yellow crystals with a purity of 99.6% (HPLC, area %).

References: [1]Patent: US2011/28511,2011,A1 .Location in patent: Page/Page column 12.

2
[ 1210838-82-6 ]
[ 183208-35-7 ]

Yield	Reaction Conditions	Operation in experiment
90%	With potassium tert-butylate; In N,N-dimethyl-formamide; at 60 - 85℃;Large scale;	Add 150 kg of DMF to a 200 L reactor, slowly add 70 kg of potassium t-butoxide, stir to 60-70 C, and slowly add 50 kg of <strong>[1210838-82-6]5-bromo-3-ethynyl-2-aminopyridine</strong>. The temperature control is not higher than 80 C , plus complete the reaction incubated 80-85 C 2 ~ 3h, TLC monitoring completion of the reaction (PE / DCM = 1/1), cooled after completion of the reaction, the reaction system was slowly added to 400kg of ice water, cooled to 10 C was stirred for 2h, filtered off with suction (suction Should difficult, adding an appropriate amount of filter aid such as diatomaceous earth, etc.), to give a brown solid crude wet weight of about 75 kg (about 95% HPLC purity). The wet product was added to a 500 L reaction vessel, 300 kg of ethyl acetate (EA) was added, 5 kg of activated carbon was added, and the mixture was heated under reflux for 30 minutes, and then suction filtered. The filter cake was washed with an appropriate amount of EA, and then the filtrate and the washing liquid were combined, and the EA was evaporated to about 250 kg under reduced pressure. (Remaining about 50kg in the kettle), cooling to 0-5 C for 2h, suction filtration, filter cake washed with appropriate amount of cold EA, blasting at 60 C to obtain a light yellow solid product 5-bromo-7-azaindole 45kg, yield 90%, HPLC purity 99.3%
		Example 7; a) Preparation of 5-bromo-7-azaindole (3 or Ia) from isolated 2-amino-5-bromo-3-iodopyridine; A suspension of 2-amino-5-bromo-3-iodopyridine (5.0 g, 16.7 mmol), bis-(triphenylphosphine)-palladium(II)-dichloride (43 mg, 0.061 mmol), copper(I)iodide (29.4 mg, 0.15 mmol) and triethylamine (2.21 g, 21.8 mmol) in dichloromethane (20 mL) was treated at 23 to 30 C. within 1 to 2 hours with a solution of 1,1-dimethyl-2-propyn-1-ol (1.85 g, 21.7 mmol) in dichloromethane (10 mL) and the resulting mixture was stirred at 25 C. for 4 hours. The mixture was diluted with dichloromethane (10 mL) and washed with water (2×25 mL). The organic phase was then treated with 1 M HCl (40 mL). The layers were separated and the organic layer was extracted with 1 M HCl (15 mL). The combined product containing aqueous layers were washed with dichloromethane (2×8 mL). The pH of the aqueous layer was adjusted to pH 7-9 by the drop wise addition of sodium hydroxide solution (28% in water). The resulting suspension was stirred at 20 C. over night and the crystals were then filtered off and washed with water (2×5 mL). The wet crystals were dissolved in N-methylpyrrolidone (50 mL) and treated within 2 hours at 60 C. and 50-100 mbar with an aqueous solution of lithium hydroxide (2.4 M, 32 mL). The resulting mixture was heated to 75 C. and stirred at this temperature and under reduced pressure (50-100 mbar) for 15-20 hours. Toluene (20 mL) and water (20 mL) were then added and the layers were separated. The aqueous layer was extracted with toluene (3×25 mL). The combined organic layers were washed with water (3×10 mL) and then concentrated to dryness. The residue was dissolved in N-methylpyrrolidone (50 mL) and treated at 60 C. with potassium tert.-butylate (3.52 g, 30.7 mmol). After stirring for 3 hours at 60 C., the mixture was cooled to ambient temperature and diluted with toluene (40 mL) and water (40 mL). The aqueous layer was separated and back extracted with toluene (3×50 mL). The combined toluene layers were washed with water (3×10 mL) and then concentrated to dryness. The residue was dissolved in a hot mixture of toluene and n-heptane (20 mL). The clear solution was cooled to -5 C. within 4 to 6 hours whereupon crystals precipitated. The suspension was stirred at -5 C. for 2-4 hours. The crystals were filtered off, washed with heptane and dried at 45 C./<30 mbars over night to afford 5-bromo-7-azaindole (2.05 g, 62% yield) as slightly yellow crystals with a purity of 99.6% (HPLC, area %).

References: [1]Patent: CN109081840,2018,A .Location in patent: Paragraph 0023; 0024.
[2]Patent: US2011/28511,2011,A1 .Location in patent: Page/Page column 12.

3
[ 1210838-82-6 ]
[ 75-26-3 ]
[ 1617499-16-7 ]

Yield	Reaction Conditions	Operation in experiment
40.9%		5-Bromo-3-(l-isopropyl- IH- [ 1 ,2 ,3] triazol-4-yl)-pyridin-2-ylamine: A mixture of isopropyl bromide (5.0 g, 40.65 mmol) and sodium azide (2.6 g, 40.65 mmol) in t-BuOH/water (1 :2) (50 mL) was stirred for 2 h at 80 C. Then the reaction mixture was cooled to room temperature, to which was added <strong>[1210838-82-6]5-bromo-3-ethynyl-pyridin-2-ylamine</strong> (0.8 g, 4.065 mmol) and Cul (catalytic amount). The reaction mixture was stirred for 16 h at 80 C. The reaction mixture was cooled to RT, diluted with EtOAc (100 mL) and washed with water (50 mL). The organic layer was washed with brine solution (50 mL), dried over anhydrous Na2S04 and solvent was evaporated under reduced pressure to afford crude compound. Crude compound was washed with diethyl ether to afford the title compound as ash colour solid. Yield: 450 mg (40.9 %) 1H NMR (DMSO-dg, 400 MHz, TMS) delta: 8.87 (IH, s), 8.09-8.08(lH, d), 8.04 (IH, s), 7.15 (2H, br), 4.90-4.83 (IH, m), 1.55 (3H, s), 1.53 (3H, s).

References: [1]Patent: WO2014/106612,2014,A1 .Location in patent: Page/Page column 29.

4
[ 1210838-82-6 ]
[ 1617499-00-9 ]

References: [1]Patent: WO2014/106612,2014,A1 .

5
[ 1210838-82-6 ]
3-(1-isopropyltriazol-4-yl)-5-[3-(morpholinomethyl)phenyl]pyridin-2-amine hydrochloride [ No CAS ]

References: [1]Patent: WO2014/106612,2014,A1 .

6
[ 1210838-82-6 ]
[ 1617499-01-0 ]

References: [1]Patent: WO2014/106612,2014,A1 .

7
[ 1210838-82-6 ]
[3-[6-amino-5-(1-isopropyltriazol-4-yl)-3-pyridyl]phenyl]morpholinomethanone hydrochloride [ No CAS ]

References: [1]Patent: WO2014/106612,2014,A1 .

8
[ 1210838-82-6 ]
[ 1617499-02-1 ]

References: [1]Patent: WO2014/106612,2014,A1 .

9
[ 1210838-82-6 ]
[ 1617499-03-2 ]

References: [1]Patent: WO2014/106612,2014,A1 .

10
[ 1210838-82-6 ]
[ 1617499-04-3 ]

References: [1]Patent: WO2014/106612,2014,A1 .

11
[ 1210838-82-6 ]
[ 1617499-06-5 ]

References: [1]Patent: WO2014/106612,2014,A1 .

12
[ 1210838-82-6 ]
2-[4-[6-amino-5-(1-isopropyltriazol-4-yl)-3-pyridyl]phenyl]-1-morpholinoethanone hydrochloride [ No CAS ]

References: [1]Patent: WO2014/106612,2014,A1 .

13
[ 1210838-82-6 ]
[ 1617499-19-0 ]

References: [1]Patent: WO2014/106612,2014,A1 .

14
[ 1210838-82-6 ]
[ 1617499-20-3 ]

References: [1]Patent: WO2014/106612,2014,A1 .

15
[ 1210838-82-6 ]
[ 1617499-21-4 ]

References: [1]Patent: WO2014/106612,2014,A1 .

16
[ 1210838-82-6 ]
[ 1617498-85-7 ]

References: [1]Patent: WO2014/106612,2014,A1 .
[2]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 4500 - 4505.

17
[ 1210838-82-6 ]
[ 1617498-86-8 ]

References: [1]Patent: WO2014/106612,2014,A1 .

18
[ 1210838-82-6 ]
[ 1617498-88-0 ]

References: [1]Patent: WO2014/106612,2014,A1 .
[2]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 4500 - 4505.

19
[ 1210838-82-6 ]
[ 1617498-89-1 ]

References: [1]Patent: WO2014/106612,2014,A1 .
[2]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 4500 - 4505.

20
[ 1210838-82-6 ]
[ 1617498-90-4 ]

References: [1]Patent: WO2014/106612,2014,A1 .
[2]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 4500 - 4505.

21
[ 1210838-82-6 ]
[ 1617498-91-5 ]

References: [1]Patent: WO2014/106612,2014,A1 .

22
[ 1210838-82-6 ]
[ 1617498-92-6 ]

References: [1]Patent: WO2014/106612,2014,A1 .

23
[ 1210838-82-6 ]
[ 1617498-93-7 ]

References: [1]Patent: WO2014/106612,2014,A1 .

24
[ 1210838-82-6 ]
[ 1617498-94-8 ]

References: [1]Patent: WO2014/106612,2014,A1 .

25
[ 1210838-82-6 ]
[ 1617498-95-9 ]

References: [1]Patent: WO2014/106612,2014,A1 .

26
[ 1210838-82-6 ]
[ 1617498-96-0 ]

References: [1]Patent: WO2014/106612,2014,A1 .

27
[ 1210838-82-6 ]
[ 1617498-97-1 ]

References: [1]Patent: WO2014/106612,2014,A1 .

28
[ 1210838-82-6 ]
[4-[6-amino-5-(1-isopropyltriazol-4-yl)-3-pyridyl]-2-chlorophenyl]morpholinomethanone hydrochloride [ No CAS ]

References: [1]Patent: WO2014/106612,2014,A1 .

29
[ 1210838-82-6 ]
[ 1617498-98-2 ]

References: [1]Patent: WO2014/106612,2014,A1 .

30
[ 1210838-82-6 ]
[ 1617498-99-3 ]

References: [1]Patent: WO2014/106612,2014,A1 .

31
[ 1210838-82-6 ]
2-((tert-butyldimethylsilyl)oxy)-N-hydroxyacetimidoyl chloride [ No CAS ]
5-bromo-3-(3-(((tert-butyldimethylsilyl)oxy)methyl)isoxazol-5-yl)pyridin-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With copper(ll) sulfate pentahydrate; sodium 2-(1,2-dihydroxyethyl)-4-hydroxy-5-oxo-2,5-dihydro-furan-3-olate; sodium hydrogencarbonate; In water; tert-butyl alcohol; at 20℃;Inert atmosphere;	Step 3: 5-Bromo-3-(3-(((tert-butyldimethylsilyl)oxy)methyl)isoxazol-5-yl)pyridin-2-amine To a suspension of <strong>[1210838-82-6]5-bromo-3-ethynylpyridin-2-amine</strong> (Intermediate C15) (500 mg, 2.54 mmol) and sodium ascorbate (0.254 ml, 0.254 mmol) in t-BuOH (10 ml) and water (10ml) under N2 was added copper(ll) sulfate pentahydrate (13mg, 0.051 mmol, 2mol%) and NaHCOs (853mg, 10.15mmol) followed by 2-((tert-butyldimethylsilyl)oxy)-N- hydroxyacetimidoyl chloride (step 3) (1.7g, 7.61 mmol, 3eq) slowly over 15mins. The mixture was stirred at RT overnight. The resulting mixture was extracted into DCM, washed with water, brine, the organic layer separated, dried over MgS04, filtered and the solvent removed under reduced pressure. The crude product was purified by flash column chromatography elution with iso-hexane:ethyl acetate (0-30%) on a 24g silica cartridge. The required fractions were combined and the solvent removed under reduced pressure to afford the title compound; LCMS: Rt = 1.62mins MS m/z 384.4 [M+H]+; Method 2minl_owpHv03.

References: [1]Patent: WO2015/162456,2015,A1 .Location in patent: Page/Page column 221-222.

32
[ 95080-93-6 ]
[ 1210838-82-6 ]
ethyl 5-(2-amino-5-bromopyridin-3-yl)isoxazole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With copper(ll) sulfate pentahydrate; sodium 2-(1,2-dihydroxyethyl)-4-hydroxy-5-oxo-2,5-dihydro-furan-3-olate; sodium hydrogencarbonate; In water; tert-butyl alcohol; at 20℃;Inert atmosphere;	Step 1 : Ethyl 5-(2-amino-5-bromopyridin-3-yl)isoxazole-3-carboxylate To a suspension of <strong>[1210838-82-6]5-bromo-3-ethynylpyridin-2-amine</strong> (Intermediate C15) (2.84 g, 14.41 mmol) and sodium ascorbate (1.441 ml, 1.441 mmol) in t-BuOH (50 ml) and water (50ml) under N2 was added copper(ll) sulfate pentahydrate (72mg, 0.288mmol, 2 mol%) and NaHC03 (4.84g, 57.7mmol) followed by (Z)-ethyl 2-chloro-2-(hydroxyimino)acetate (2.2g, 14.4mmol, 1 eq) slowly over 15mins.The resulting mixture was stirred at room temp for 1 hour. To the mixture was slowly added further (Z)-ethyl 2-chloro-2-(hydroxyimino)acetate (2.2g, 14.4mmol, 1eq) over 15mins and stirring continued for a further hour. Further (Z)-ethyl 2-chloro-2-(hydroxyimino)acetate (2.2g, 14.4mmol, 1eq) was added over 15mins and the mixture was stirred at RT overnight. The mixture was extracted into ethyl acetate, washed with water, brine, the organic layer separated, dried over MgS04, filtered and the solvent removed under reduced pressure. The crude product was purified by flash column chromatography elution with iso-hexane:ethyl acetate (0-40%) on a 80g silica cartridge. The required fractions were combined and the solvent removed under reduced pressure. A solid crystallised on concentration. The solid was collected by filtration to yield the title compound as orange crystals; LCMS: Rt = 1.18mins MS m/z 314.1 [M+H]+; Method 2minl_owpHv03.

References: [1]Patent: WO2015/162456,2015,A1 .Location in patent: Page/Page column 223.

33
[ 44637-25-4 ]
[ 1210838-82-6 ]
5-bromo-3-(3-(trifluoromethyl)isoxazol-5-yl)pyridin-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With copper(ll) sulfate pentahydrate; sodium 2-(1,2-dihydroxyethyl)-4-hydroxy-5-oxo-2,5-dihydro-furan-3-olate; sodium hydrogencarbonate; In water; tert-butyl alcohol; at 20℃;Inert atmosphere;	Step 5: 5-Bromo-3-(3-(trifluoromethyl)isoxazol-5-yl)pyridin-2-amine To a 50 mL round-bottomed flask was added <strong>[1210838-82-6]5-bromo-3-ethynylpyridin-2-amine</strong> (500 mg, 2.54 mmol), and sodium ascorbate (0.254 ml, 0.254 mmol) in t-BuOH (10 ml) and water (10ml) under N2 to give a brown suspension. To the mixture was added copper(ll) sulfate pentahydrate (13mg, 0.051 mmol, 2mol%) and NaHC03 (923mg, 10.99mmol) followed by 2,2,2-trifluoro-N-hydroxyacetimidoyl bromide (1.239g, 2.54mmol) in 250muIota portions over 15mins. The reaction mixture was stirred at RT for 1 hour. To the mixture was added 2,2,2- trifluoro-N-hydroxyacetimidoyl bromide (700mg, 1.433mmol) and stirring continued at RT overnight. The resulting mixture was extracted into ethyl acetate, washed with water, brine, the organic layer separated, dried over MgS04, filtered and the solvent removed under reduced pressure. The crude product was purified by flash column chromatography elution with iso hexane:ethyl acetate (0-20%) on a 12g silica cartridge. The product fractions were combined and the solvent removed under reduced pressure to yield a yellow solid. The product was purified by a second flash column chromatography,, elution with iso hexane:ethyl acetate (0-20%) on a 12g silica cartridge. The fractions were combined and the solvent removed under reduced pressure to yield the title compound as a yellow solid; LCMS: Rt = 1.20mins MS m/z 308.4 [M+H]+; Method 2minl_owpHv01.

References: [1]Patent: WO2015/162456,2015,A1 .Location in patent: Page/Page column 243-244.

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[ 51451-05-9 ]
[ 1210838-82-6 ]
5-bromo-3-(3-(chloromethyl)isoxazol-5-yl)pyridin-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hypochlorite; In tetrahydrofuran; at 0 - 20℃;Inert atmosphere;	Step 2: 5-Bromo-3-(3-(chloromethyl)isoxazol-5-yl)pyridin-2-amine To a 100 ml_ round-bottomed flask was added <strong>[1210838-82-6]5-bromo-3-ethynylpyridin-2-amine</strong> (Intermediate C15) (1.3 g, 6.60 mmol), and 2-chloroacetaldehyde oxime (mixture of isomers, from Step 1)(1.424 g, 9.90 mmol) in THF (15 ml) under N2 to give a brown solution. To the mixture at 0C was then added NaOCI (30ml) dropwise over 90mins. The mixture was stirred at RT overnight. The resulting mixture was extracted into DCM, washed with water, brine, the organic layer separated, dried over MgS04, filtered and the solvent removed under reduced pressure. The crude product was purified by flash column chromatography elution with iso- hexane:ethyl acetate (0-50%) on a 40g silica cartridge. The product fractions were combined and the solvent removed under reduced pressure to yield the title compound as a brown oil; LCMS: Rt = 1.21 mins MS m/z 290.1 (Br isotope) [M+H]+; Method 2minLowpHv03.

References: [1]Patent: WO2015/162456,2015,A1 .Location in patent: Page/Page column 245.

35
[ 381233-96-1 ]
[ 1210838-82-6 ]

References: [1]Patent: WO2015/162456,2015,A1 .

Historical Records

Technical Information

• Alkyl Halide Occurrence • Buchwald-Hartwig C-N Bond and C-O Bond Formation Reactions • Chan-Lam Coupling Reaction • General Reactivity • Grignard Reaction • Hiyama Cross-Coupling Reaction • Hydride Reductions • Kinetics of Alkyl Halides • Kumada Cross-Coupling Reaction • Leuckart-Wallach Reaction • Mannich Reaction • Petasis Reaction • Preparation of Amines • Reactions of Alkyl Halides with Reducing Metals • Reactions of Amines • Reactions of Dihalides • Specialized Acylation Reagents-Vilsmeier Reagent • Stille Coupling • Substitution and Elimination Reactions of Alkyl Halides • Suzuki Coupling • Ugi Reaction

Related Functional Groups of
[ 1210838-82-6 ]

Alkynyls

A246025 [67346-74-1]

3-Ethynylpyridin-2-amine

Similarity: 0.82

A159003 [1094679-27-2]

4-Ethynylpyridin-2-amine

Similarity: 0.68

A673049 [82454-61-3]

5-Ethynylpyridin-2-amine

Similarity: 0.64

A655024 [2510-23-8]

3-Ethynylpyridine

Similarity: 0.62

A149507 [111770-86-6]

5-Bromo-2-ethynylpyridine

Similarity: 0.61

Bromides

A339583 [3430-21-5]

5-Bromo-3-methylpyridin-2-amine

Similarity: 0.87

A504055 [374537-97-0]

2-Amino-5-bromo-3,4-dimethylpyridine

Similarity: 0.81

A146093 [335031-01-1]

2-Amino-5-bromo-3-(hydroxymethyl)pyridine

Similarity: 0.79

A302728 [443956-55-6]

2-Amino-5-bromo-3-(hydroxymethyl)pyridine hydrobromide

Similarity: 0.79

A216085 [1072-97-5]

5-Bromopyridin-2-amine

Similarity: 0.76

Amines

A339583 [3430-21-5]

5-Bromo-3-methylpyridin-2-amine

Similarity: 0.87

A246025 [67346-74-1]

3-Ethynylpyridin-2-amine

Similarity: 0.82

A504055 [374537-97-0]

2-Amino-5-bromo-3,4-dimethylpyridine

Similarity: 0.81

A146093 [335031-01-1]

2-Amino-5-bromo-3-(hydroxymethyl)pyridine

Similarity: 0.79

A302728 [443956-55-6]

2-Amino-5-bromo-3-(hydroxymethyl)pyridine hydrobromide

Similarity: 0.79

Related Parent Nucleus of
[ 1210838-82-6 ]

Pyridines

A339583 [3430-21-5]

5-Bromo-3-methylpyridin-2-amine

Similarity: 0.87

A246025 [67346-74-1]

3-Ethynylpyridin-2-amine

Similarity: 0.82

A504055 [374537-97-0]

2-Amino-5-bromo-3,4-dimethylpyridine

Similarity: 0.81

A146093 [335031-01-1]

2-Amino-5-bromo-3-(hydroxymethyl)pyridine

Similarity: 0.79

A302728 [443956-55-6]

2-Amino-5-bromo-3-(hydroxymethyl)pyridine hydrobromide

Similarity: 0.79

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CAS No.: 1210838-82-6

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