55876-84-1|Methyl 5-(bromomethyl)picolinate| Ambeed

There will be a HazMat fee per item when shipping a dangerous goods. The HazMat fee will be charged to your UPS/DHL/FedEx collect account or added to the invoice unless the package is shipped via Ground service. Ship by air in Excepted Quantity (each bottle), which is up to 1g/1mL for class 6.1 packing group I or II, and up to 25g/25ml for all other HazMat items.

Type	HazMat fee for 500 gram (Estimated)
Excepted Quantity	USD 0.00
Limited Quantity	USD 15-60
Inaccessible (Haz class 6.1), Domestic	USD 80+
Inaccessible (Haz class 6.1), International	USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic	USD 100+
Accessible (Haz class 3, 4, 5 or 8), International	USD 200+

Structure of 55876-84-1

*Storage: {[sel_prStorage]}

*Shipping: {[sel_prShipping]}

4.5 *For Research Use Only !

{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]} Purity: {[proInfo.pro_purity]}

Change View

Size	Price	VIP Price	US Stock	Global Stock	In Stock
{[ item.pr_size ]}		Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}

US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days

{[ item.pr_size ]}

In Stock

- +

Please Login or Create an Account to: See VIP prices and availability

US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks

Quality Control of [ 55876-84-1 ] Purity: 96% SDS Specification

COA

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

NMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

CNMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

HPLC

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

LC-MS

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

1-2 Day Shipping
High Quality
Technical Support

Product Details of [ 55876-84-1 ]

CAS No. :	55876-84-1
Formula :	C₈H₈BrNO₂
M.W :	230.06
SMILES Code :	O=C(OC)C1=NC=C(CBr)C=C1
MDL No. :	MFCD07367952
InChI Key :	SIMKVUKTEMRUSF-UHFFFAOYSA-N
Pubchem ID :	19699469

Safety of [ 55876-84-1 ]

GHS Pictogram:
Signal Word:	Danger
Hazard Statements:	H302-H314
Precautionary Statements:	P501-P260-P270-P264-P280-P303+P361+P353-P301+P330+P331-P363-P301+P312+P330-P304+P340+P310-P305+P351+P338+P310-P405
Class:	8
UN#:	1759
Packing Group:	Ⅱ

Computational Chemistry of [ 55876-84-1 ] Show Less

Physicochemical Properties

Num. heavy atoms	12
Num. arom. heavy atoms	6
Fraction Csp3	0.25
Num. rotatable bonds	3
Num. H-bond acceptors	3.0
Num. H-bond donors	0.0
Molar Refractivity	48.35
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	39.19 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.96
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	2.05
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	1.61
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.	1.13
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	2.2
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.79

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.73
Solubility	0.429 mg/ml ; 0.00186 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.	-2.5
Solubility	0.725 mg/ml ; 0.00315 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	-3.37
Solubility	0.099 mg/ml ; 0.000431 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.	-6.25 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	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)	2.02

Application In Synthesis of [ 55876-84-1 ]

* 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 [ 55876-84-1 ]

[ 55876-84-1 ] Synthesis Path-Downstream 1~35

3
[ 72621-20-6 ]
[ 55876-84-1 ]
5-(4'-dodecyloxy-biphenyl-4-yloxymethyl)-pyridine-2-carboxylic acid methyl ester [ No CAS ]

References: [1]Journal of Materials Chemistry,2001,vol. 11,p. 741 - 748.

4
[ 29681-38-7 ]
[ 55876-84-1 ]

Yield	Reaction Conditions	Operation in experiment
66%	With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); In tetrachloromethane; for 5h;Reflux;	A mixture of methyl 2-methylisonicotinate (leq) and a,a'-Azoisobutyronitrile (AIBN) (10%) was dissolved in carbontetrachloride (CC14). The solution was heated at 48C and N-bromosuccinimide (NBS) (1.1 eq) solution in CC14 was added drop wise and stirred for 5 hours. The reaction was cooled to room temperature and the solvent evaporated. The mixture was then extracted using dichloromethane and water followed by washing the organic layer with brine. The organic layer was dried over sodium sulfate, filtered, evaporated and the crude product was purified using SiO2 column chromatography and eluted with the solvent system EtOAc: hexanes = 2:3 to obtain pure product as white powder and the yield was 66%. 1H-NMR (400 MHz, DMSO-d6): d 8.78 (t, J= 1.48 Hz, 1H), 8.06 (d, J= 1.36 Hz, 2H), 4.82 (s, 2H), 3.89 (s, 3H). HRMS (ESI) m/z found 229.98 [M+H]+, Calculated 230.0586 [M]+.
57%	With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); In tetrachloromethane; at 80℃; for 16h;	5-(Bromomethyl)pyridine-2-carboxylate In a 500-mL round bottom flask, NBS (14.13 g, 79.38 mmol, 1.20 equiv) and AIBN (217 mg, 1.32 mmol, 0.02 equiv) were added to a solution of methyl 5-methylpyridine-2-carboxylate (10 g, 66.15 mmol, 1.00 equiv) in CCl4 (200 mL) at room temperature. The resulting solution was stirred for 16 h at 80 C. After the reaction was done, the reaction mixture was concentrated under reduced pressure. The residue was purified in a silica gel column eluting with ethyl acetate in petroleum ether (5% to 25% gradient) to afford methyl 5-(bromomethyl)pyridine-2-carboxylate (9.6 g, 57%) as yellow solid. MS: m/z=229.9 [M+H]+
50%	With N-Bromosuccinimide;VAZO; In tetrachloromethane; for 18h;Heating / reflux;	To a solution of 5-methylpyridirie-2-carboxylic acid methyl ester (140 mg, 0.93 mmol) in CCl4 (8 mL) was added NBS (181 mg, 1.02 mmol) and VAZO (23 mg, 0.09 mmol). The reaction was stirred at reflux for 18 h. Standard work-up and purification by flash chromatography on silica gel (10% ether in CH2Cl2) afforded 5-bromomethylpyridine-2- carboxylic acid methyl ester (107 mg, 50%).

24%	With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; for 18h;Reflux;	INTERMEDIATE 37 - PREPARATION of Methyl 5-(bromomethyl)picolinate. To a mixture of methyl 5-methylpicolinate (1.25 g; 8.27 mmol) in carbon tetrachloride (45 mL) was added N-bromosuccinimide (1.78 g, 9.92 mmol) and benzoyl peroxide (0.205 g; 0.827 mmol). The mixture was refluxed for 18 hours and the resulting suspension was concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (eluent 0 to 8% ethyl acetate in dichloromethane) to 0.450g (24%) of methyl 5- (bromomethyl)picolinate as a beige solid.ESI/APCI(+): 230 (M+H).
24%	With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; for 18h;Reflux;	To a mixture of methyl 5-methylpicolinate (1.25 g; 8.27 mmol) in carbon tetrachloride (45 mL) was added N-bromosuccinimide (1.78 g, 9.92 mmol) and benzoyl peroxide (0.205 g; 0.827 mmol). The mixture was refluxed for 18 hours and the resulting suspension was concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (eluent 0 to 8% ethyl acetate in dichloromethane) to 0.450 g (24%) of methyl 5-(bromomethyl)picolinate as a beige solid. [0623] ESI/APCI(+): 230 (M+H).
11%	With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane;Reflux;	Example 8. Synthesis of 1-548-101. Into a 2000-mL 4-necked round-bottom flask, was placed a solution of methyl 5-methylpicolinate (85 g, 539.68 mmol, 1.00 equiv, 96%) in CC14 (1000 mL), N-bromosuccinimide (1 10 g, 617.98 mmol, 1.10 equiv), and benzoyl peroxide (3.5 g, 14.45 mmol, 0.03 equiv). The resulting solution was heated to reflux overnight. The solids were removed by filtration. The filtrate was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1 :30-l :5). This resulted in 15 g (1 1%) of methyl 5-(bromomethyl)picolinate as a light-yellow solid.LC-MS: (ES, m/z): 232 [M+H]+

References: [1]Patent: WO2019/182938,2019,A1 .Location in patent: Page/Page column 35.
[2]Patent: US2016/96834,2016,A1 .Location in patent: Paragraph 0328.
[3]Patent: WO2007/22371,2007,A2 .Location in patent: Page/Page column 90.
[4]Patent: WO2012/80221,2012,A1 .Location in patent: Page/Page column 84.
[5]Patent: US2013/274260,2013,A1 .Location in patent: Paragraph 0622-0623.
[6]Patent: WO2013/3505,2013,A1 .Location in patent: Page/Page column 58.

5
[ 768-35-4 ]
[ 55876-84-1 ]
[ 1382991-46-9 ]

Yield	Reaction Conditions	Operation in experiment
40%	With N-ethyl-N,N-diisopropylamine;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 130℃; for 0.333333h;Microwave irradiation;	INTERMEDIATE 38 - PREPARATION of methyl 5-(3-fluorobenzyl)picolinate. A mixture of 3-fluorophenylboronic acid (0.319 g; 2.28 mmol), methyl 5- (bromomethyl)picolinate (0.350 g; 0.230 mmol), tetrakis-(triphenylphosphine)-palladium(0) (0.175; 0.152 mmol) and N,N diisopropylethylamine (0.524 g; 3.04 mmol) in dimethoxyethane (9 mL) and water (3 mL) was irradiated in a microwave oven at 130°C for 20 minutes. The resulting solution was partitioned between water and ethyl acetate. The organic layer was separated and concentrated under reduced pressure. The crude residue was purified by flash chromatography on silica gel (eluent 1 to 10 percent ethyl acetate in dichlomethane) to afford 0.149 g (40percent) of the title compound as a yellow oil.ESI/APCI(+): 246 (M+H), 268(M+Na).
40%	With tetrakis(triphenylphosphine) palladium(0); N-ethyl-N,N-diisopropylamine; In 1,2-dimethoxyethane; water; at 130℃; for 0.333333h;Microwave irradiation;	A mixture of 3-fluorophenylboronic acid (0.319 g; 2.28 mmol), <strong>[55876-84-1]methyl 5-(bromomethyl)picolinate</strong> (0.350 g; 0.230 mmol), tetrakis-(triphenylphosphine)-palladium(0) (0.175; 0.152 mmol) and N,N diisopropylethylamine (0.524 g; 3.04 mmol) in dimethoxyethane (9 mL) and water (3 mL) was irradiated in a microwave oven at 130° C. for 20 minutes. The resulting solution was partitioned between water and ethyl acetate. The organic layer was separated and concentrated under reduced pressure. The crude residue was purified by flash chromatography on silica gel (eluent 1 to 10percent ethyl acetate in dichlomethane) to afford 0.149 g (40percent) of the title compound as a yellow oil. [0625] ESI/APCI(+): 246 (M+H), 268 (M+Na).

References: [1]Patent: WO2012/80221,2012,A1 .Location in patent: Page/Page column 84.
[2]Patent: US2013/274260,2013,A1 .Location in patent: Paragraph 0624-0625.

6
[ 589-93-5 ]
[ 55876-84-1 ]

References: [1]Patent: WO2012/80221,2012,A1 .
[2]Patent: US2013/274260,2013,A1 .

7
[ 55876-84-1 ]
[ 1382991-47-0 ]

References: [1]Patent: WO2012/80221,2012,A1 .
[2]Patent: US2013/274260,2013,A1 .

8
[ 55876-84-1 ]
[ 1417421-45-4 ]

References: [1]Patent: WO2013/3505,2013,A1 .

9
[ 55876-84-1 ]
[ 1417421-49-8 ]

References: [1]Patent: WO2013/3505,2013,A1 .

10
[ 55876-84-1 ]
[ 1417421-51-2 ]

References: [1]Patent: WO2013/3505,2013,A1 .

11
[ 55876-84-1 ]
[ 1417419-77-2 ]

References: [1]Patent: WO2013/3505,2013,A1 .

12
[ 620-17-7 ]
[ 55876-84-1 ]
[ 1417421-44-3 ]

Yield	Reaction Conditions	Operation in experiment
92%	With potassium carbonate; In acetonitrile; at 85℃; for 2h;	Example 9. Synthesis of 1-548-102. Into a 50-mL round-bottom flask, was placed a solution of <strong>[55876-84-1]methyl 5-(bromomethyl)picolinate</strong> (500 mg, 2.09 mmol, 1.00 equiv, 96percent) in acetonitrile (20 mL), 3-ethylphenol (280 mg, 2.29 mmol, 1.05 equiv), and potassium carbonate (900 mg, 6.51 mmol, 3.00 equiv). The resulting solution was stirred for 2 h at 85°C. The mixture was concentrated under vacuum. The residue was diluted with 30 mL of water and extracted with 2x20 mL of ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate and concentrated under vacuum. This resulted in 0.6 g (92percent) of methyl 5-((3- ethylphenoxy)methyl)picolinate as a brown solid.LC-MS: (ES, m/z): 272 [M+H]+

References: [1]Patent: WO2013/3505,2013,A1 .Location in patent: Page/Page column 58; 59.

13
[ 55876-84-1 ]
[ 108-39-4 ]
[ 1417421-46-5 ]

Yield	Reaction Conditions	Operation in experiment
89%	With potassium carbonate; In acetonitrile; for 2h;Reflux;	Example 12. Synthesis of 1-554-1. Into a 50-mL round-bottom flask, was placed a solution of <strong>[55876-84-1]methyl 5-(bromomethyl)picolinate</strong> (500 mg, 2.17 mmol, 1.00 equiv) in CH3CN (25 mL), m-cresol (250 mg, 2.31 mmol, 1.05 equiv), and potassium carbonate (900 mg, 6.52 mmol, 3.00 equiv). The solution was heated to reflux for 2 h in an oil bath. The resulting mixture was concentrated under vacuum and diluted with 50 mL of H20. The resulting solution was extracted with 3x20 mL of ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate and concentrated under vacuum. This resulted in 0.6 g (89percent) of methyl 5-(m- tolyloxymethyl)picolinate as a brown solid.LC-MS: (ES, m/z): [M+H]+ 258

References: [1]Patent: WO2013/3505,2013,A1 .Location in patent: Page/Page column 60.

14
[ 433939-27-6 ]
[ 55876-84-1 ]
[ 1417421-48-7 ]

Yield	Reaction Conditions	Operation in experiment
77%	With potassium carbonate; In acetonitrile; at 85℃; for 1h;	Example 15. Synthesis of 1-546-1. Into a 50-mL round-bottom flask, was placed <strong>[55876-84-1]methyl 5-(bromomethyl)picolinate</strong> (500 mg, 2.17 mmol, 1.00 equiv), 3-bromo-5-fluorophenol (440 mg, 2.30 mmol, 1.06 equiv), CH3CN (6 mL), and potassium carbonate (900 mg, 6.52 mmol, 3.00 equiv). The resulting solution was stirred for 60 min at 85°C. The mixture was concentrated under vacuum and the residue was diluted with 20 mL of H20. The resulting solution was extracted with 3x20 mL of ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate. The solids were filtered out. The resulting mixture was concentrated under vacuum. This resulted in 0.62 g (77percent) of methyl 5-((3-bromo-5- fluorophenoxy)methyl)picolinate as a yellow solid.LC-MS: ( +

References: [1]Patent: WO2013/3505,2013,A1 .Location in patent: Page/Page column 61-62.

15
[ 827-99-6 ]
[ 55876-84-1 ]
[ 1417421-50-1 ]

Yield	Reaction Conditions	Operation in experiment
74%	With potassium carbonate; In acetonitrile; at 85℃; for 0.5h;	Example 18. Synthesis of 1-549-1. Into a 50-mL round-bottom flask, was placed <strong>[55876-84-1]methyl 5-(bromomethyl)picolinate</strong> (500 mg, 2.17 mmol, 1.00 equiv), 3-(trifluoromethoxy)phenol (410 mg, 2.30 mmol, 1.06 equiv), CH3CN (6 mL), and potassium carbonate (900 mg, 6.52 mmol, 3.00 equiv). The resulting solution was stirred for 30 min at 85°C in an oil bath. The resulting mixture was concentrated under vacuum. The residue was diluted with 20 mL of H20 and extracted with 2x20 mL of ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate. The solids were filtered out. The filtrate was concentrated under vacuum. This resulted in 0.56 g (74percent) of methyl 5-((3-(trifluoromethoxy)phenoxy)methyl)picolinate as a yellow-tan solid.

References: [1]Patent: WO2013/3505,2013,A1 .Location in patent: Page/Page column 63; 64.

16
[ 18368-64-4 ]
[ 55876-84-1 ]

References: [1]Patent: WO2013/3505,2013,A1 .

17
[ 55876-84-1 ]
[5-[(4-methylpiperazin-1-yl)methyl]pyridin-2-yl]methanol [ No CAS ]

References: [1]Patent: US2016/96834,2016,A1 .

18
[ 55876-84-1 ]
5-[(4-methylpiperazin-1-yl)methyl]pyridine-2-carbaldehyde [ No CAS ]

References: [1]Patent: US2016/96834,2016,A1 .

19
[ 109-01-3 ]
[ 55876-84-1 ]
methyl 5-[(4-methylpiperazin-1-yl)methyl]pyridine-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
49%	With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 20℃; for 4h;	Methyl 5-[(4-methylpiperazin-1-yl)methyl]pyridine-2-carboxylate In a 50-mL round bottom flask with magnetic stir bar, <strong>[55876-84-1]methyl 5-(bromomethyl)pyridine-2-carboxylate</strong> (940 mg, 4.09 mmol, 1.00 equiv) and 1-methylpiperazine (449.6 mg, 4.49 mmol, 1.10 equiv) were dissolved in ACN (10 mL), to which DIEA (790.8 mg, 6.12 mmol, 1.50 equiv) was added at room temperature. The resulting solution was stirred for 4 h at room temperature. After the reaction was done, the reaction mixture was concentrated under reduced pressure. The residue was purified in a silica gel column eluting with methanol in dichloromethane (1percent to 10percent gradient) to afford methyl 5-[(4-methylpiperazin-1-yl)methyl]pyridine-2-carboxylate (500 mg, 49percent) as brown solid.

References: [1]Patent: US2016/96834,2016,A1 .Location in patent: Paragraph 0329.

20
[ 55876-84-1 ]
5-(chloromethyl)picolinoyl chloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		IN NaOH solution was added to a THF (lmL) solution of methyl 5-(bromomethyl) pyridine-2-carboxylate {Ark Pharm, catAK153186, 20 mg, 0.08 mmol) and the mixture was allowed to stir at rt for lh. The mixture was acidified with IN HC1 solution until pH = 4, and then the mixture was extracted with DCM. The organic layers were combined, dried and concentrated. To the residue was added 2.0 M oxalyl chloride in DCM (0.10 mL, 0.20 mmol) and N,N-dimethylformamide (0.6 \L, 0.008 mmol) at 0 °C under N2. The mixture was allowed to stir at rt for 2h, and then the mixture was concentrated and the residue was used for next step without further purification.

References: [1]Patent: WO2017/106634,2017,A1 .Location in patent: Page/Page column 117.

21
[ 55876-84-1 ]
5-(chloromethyl)-N-(2-cyano-3-cyclohexylphenyl)pyridine-2-carboxamide [ No CAS ]

References: [1]Patent: WO2017/106634,2017,A1 .

22
[ 55876-84-1 ]
N-(2-cyano-3-cyclohexylphenyl)-5-[(2-hydroxyethyl)amino]methyl}pyridine-2-carboxamide trifluoroacetic acid salt [ No CAS ]

References: [1]Patent: WO2017/106634,2017,A1 .

23
[ 55876-84-1 ]
methyl 2-(2-(6-((bis(pyridin-2-ylmethyl)amino)methyl)nicotinamido)acetamido)acetate [ No CAS ]