[ CAS No. 42732-49-0 ] {[proInfo.proName]}

Name: 42732-49-0|3-Hydroxy-5-picoline|98%
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Quality Control of [ 42732-49-0 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 42732-49-0 ]

Product Details of [ 42732-49-0 ]

CAS No. :	42732-49-0	MDL No. :	MFCD00661297
Formula :	C₆H₇NO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	RYJNCIGFPWGVPA-UHFFFAOYSA-N
M.W :	109.13	Pubchem ID :	224753
Synonyms :

Calculated chemistry of [ 42732-49-0 ]

Physicochemical Properties

Num. heavy atoms :	8
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.17
Num. rotatable bonds :	0
Num. H-bond acceptors :	2.0
Num. H-bond donors :	1.0
Molar Refractivity :	31.23
TPSA :	33.12 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.36 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.1
Log Po/w (XLOGP3) :	0.86
Log Po/w (WLOGP) :	1.1
Log Po/w (MLOGP) :	0.13
Log Po/w (SILICOS-IT) :	1.38
Consensus Log Po/w :	0.91

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-1.61
Solubility :	2.66 mg/ml ; 0.0244 mol/l
Class :	Very soluble
Log S (Ali) :	-1.14
Solubility :	7.92 mg/ml ; 0.0726 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.77
Solubility :	1.84 mg/ml ; 0.0169 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.11

Safety of [ 42732-49-0 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 42732-49-0 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 42732-49-0 ]
Downstream synthetic route of [ 42732-49-0 ]

[ 42732-49-0 ] Synthesis Path-Upstream 1~9

1
[ 100958-68-7 ]
[ 42732-49-0 ]

Reference： [1] Journal of the American Chemical Society, 1959, vol. 81, p. 740,742

2
[ 6443-85-2 ]
[ 42732-49-0 ]

Reference： [1] Journal of the American Chemical Society, 1959, vol. 81, p. 740,742

3
[ 99310-62-0 ]
[ 42732-49-0 ]

Reference： [1] Journal of the American Chemical Society, 1959, vol. 81, p. 740,742

4
[ 6635-88-7 ]
[ 42732-49-0 ]

Reference： [1] Journal of the American Chemical Society, 1959, vol. 81, p. 740,742

5
[ 6959-48-4 ]
[ 42732-49-0 ]

Reference： [1] Journal of the American Chemical Society, 1959, vol. 81, p. 740,742

6
[ 458569-34-1 ]
[ 42732-49-0 ]

Reference： [1] Nippon Kagaku Zasshi, 1953, vol. 74, p. 446[2] Chem.Abstr., 1954, p. 6442

7
[ 66527-53-5 ]
[ 42732-49-0 ]

Reference： [1] Chemical Communications, 2017, vol. 53, # 48, p. 6417 - 6420

8
[ 1572-63-0 ]
[ 42732-49-0 ]

Reference： [1] Chemical Communications, 2017, vol. 53, # 48, p. 6417 - 6420

9
[ 1003-73-2 ]
[ 42732-49-0 ]

Reference： [1] Nippon Kagaku Zasshi, 1953, vol. 74, p. 446[2] Chem.Abstr., 1954, p. 6442

[ 42732-49-0 ] Synthesis Path-Downstream 1~76

1
[ 42732-49-0 ]
[ 98139-03-8 ]

Reference： [1]Roczniki Chemii,1956,vol. 30,p. 475,479
Chem.Abstr.,1957,p. 14722

2
[ 100958-68-7 ]
[ 42732-49-0 ]

Reference： [1]Journal of the American Chemical Society,1959,vol. 81,p. 740,742

3
[ 458569-34-1 ]
[ 42732-49-0 ]

Reference： [1]Nippon Kagaku Zasshi,1953,vol. 74,p. 446
Chem.Abstr.,1954,p. 6442

4
[ 42732-49-0 ]
[ 15128-88-8 ]

Yield	Reaction Conditions	Operation in experiment
89%	With sulfuric acid; nitric acid; at 0 - 20℃;	Example 45A 5-Methyl-2-nitropyridin-3-ol With ice-cooling, 25 g (0.23 mol) of <strong>[42732-49-0]5-methylpyridin-3-ol</strong> were initially charged in 226 ml (4.12 mol) of concentrated sulphuric acid, and the mixture was then warmed to RT. After the starting material had been dissolved completely, the reaction mixture was once more cooled to 0 C. At 0 C. to 10 C., 14.25 ml (0.34 mol) of fuming nitric acid were then slowly added dropwise, and the mixture was warmed to 15 C. over 3.5 hours. The mixture was stirred at RT overnight. The reaction solution was poured onto 1000 g of ice and extracted twice with in each case 500 ml of ethyl acetate. The combined organic phases were dried and concentrated. This gave 31.5 g of the target compound (89% of theory). LC-MS (Method 14): Rt=1.21 min MS (ESpos): m/z=155 (M+H)+
	With nitric acid;	Example 45A 5-Methyl-2-nitropyridin-3-ol With ice-cooling, 25 g (0.23 mol) of <strong>[42732-49-0]5-methylpyridin-3-ol</strong> were initially charged in 226 ml (4.12 mol) of concentrated sulphuric acid, and the mixture was then warmed to RT. After the starting material had been dissolved completely, the reaction mixture was once more cooled to 0 C. At 0 C. to 10 C., 14.25 ml (0.34 mol) of fuming nitric acid were then added slowly dropwise, and the mixture was warmed to 15 C. over 3.5 hours. The mixture was stirred at RT overnight. The reaction solution was poured onto 1000 g of ice and extracted twice with in each case 500 ml of ethyl acetate. The combined organic phases were dried and concentrated. This gave 31.5 g of the target compound (89% of theory). LC-MS (Method 14): Rt=1.21 min MS (ESpos): m/z=155 (M+H)+

Reference： [1]Patent: US2017/57954,2017,A1 .Location in patent: Paragraph 0724; 0725; 0726; 0727
[2]Journal of Medicinal Chemistry,1987,vol. 30,p. 2031 - 2046
[3]Patent: US2017/217954,2017,A1

5
[ 42732-49-0 ]
[ 176770-19-7 ]
5-methyl-3-pyridyl 6-chloromethyl-2-oxo-2H-1-benzopyran-3-carboxylate [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 4161 - 4171

8
5-methyl-pyridine-sulfonic acid [ No CAS ]
[ 42732-49-0 ]

Reference： [1]Journal of Biological Chemistry,1951,vol. 191,p. 71,85

9
optically inactive bis-<2-hydroxy-propyl>-amine [ No CAS ]
[ 42732-49-0 ]

Reference： [1]Patent: US2557076,1949,

10
[ 42732-49-0 ]
[ 161511-85-9 ]
[ 191162-65-9 ]

Reference： [1]Journal of labelled compounds and radiopharmaceuticals,2001,vol. 44,p. S251 - S253

11
[ 42732-49-0 ]
[ 20348-17-8 ]

Reference： [1]Journal of Medicinal Chemistry,1987,vol. 30,p. 2031 - 2046

12
[ 42732-49-0 ]
[ 98554-59-7 ]

Reference： [1]Roczniki Chemii,1956,vol. 30,p. 475,479
Chem.Abstr.,1957,p. 14722

13
[ 1003-73-2 ]
[ 42732-49-0 ]

Reference： [1]Nippon Kagaku Zasshi,1953,vol. 74,p. 446
Chem.Abstr.,1954,p. 6442

14
[ 6443-85-2 ]
[ 42732-49-0 ]

Reference： [1]Journal of the American Chemical Society,1959,vol. 81,p. 740,742

15
[ 99310-62-0 ]
[ 42732-49-0 ]

Reference： [1]Journal of the American Chemical Society,1959,vol. 81,p. 740,742

16
[ 6635-88-7 ]
[ 42732-49-0 ]

Reference： [1]Journal of the American Chemical Society,1959,vol. 81,p. 740,742

17
[ 6959-48-4 ]
[ 42732-49-0 ]

Reference： [1]Journal of the American Chemical Society,1959,vol. 81,p. 740,742

18
[ 42732-49-0 ]
[ 585-79-5 ]
[ 228401-34-1 ]

Yield	Reaction Conditions	Operation in experiment
13%	With potassium carbonate;copper(l) iodide; In DMF (N,N-dimethyl-formamide); for 18h;Heating / reflux;	To a solution of <strong>[42732-49-0]3-hydroxy-5-methylpyridine</strong> (5.0 g, 45.8 mmol), 1-bromo-3-nitrobenzene (12.0 g, 59.6 mmol) and copper(I) iodide (10.0 g, 73.3 mmol) in anh DMF (50 mL) was added K2CO3 (13.0 g, 91.6 mmol) in one portion. The mixture was heated at the reflux temp. with stirring for 18 h and then allowed to cool to room temp. The mixture was then poured into water (200 mL) and extracted with EtOAc (3 x 150 mL). The combined organics were sequentially washed with water (3 x 100 mL) and a saturated NaCl solution (2 x 100 mL), dried (Na2SO4), and concentrated in vacuo . The resulting oil was purified by flash chromatography (30% EtOAc/70% hexane) to afford the desired product (1.2 g, 13%).[40.1]

Reference： [1]Patent: EP1449834,2004,A2 .Location in patent: Page 25

19
[ 42732-49-0 ]
[ 585-79-5 ]
3-(5-Methyl-3-pyridinyloxy)-1-nitrobenzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
13%	With potassium carbonate;copper(I) iodide; In N,N-dimethyl-formamide;	Step 1. 3-(5-Methyl-3-pyridinyloxy)-1-nitrobenzene To a solution of <strong>[42732-49-0]3-hydroxy-5-methylpyridine</strong> (5.0 g, 45.8 mmol), 1-bromo-3-nitrobenzene (12.0 g, 59.6 mmol) and copper(I) iodide (10.0 g, 73.3 mmol) in anh DMF (50 mL) was added K2CO3 (13.0 g, 91.6 mmol) in one portion. The mixture was heated at the reflux temp. with stirring for 18 h and then allowed to cool to room temp. The mixture was then poured into water (200 mL) and extracted with EtOAc (3150 mL). The combined organics were sequentially washed with water (3100 mL) and a saturated NaCl solution (2*100 mL), dried (Na2SO4), and concentrated in vacuo. The resulting oil was purified by flash chromatography (30% EtOAc/70% hexane) to afford the desired product (1.2 g, 13%).
13%	With potassium carbonate;copper(I) iodide; In N,N-dimethyl-formamide;	Step 1. 3-(5-Methyl-3-pyridinyloxy)-1-nitrobenzene To a solution of <strong>[42732-49-0]3-hydroxy-5-methylpyridine</strong> (5.0 g, 45.8 mmol), 1-bromo-3-nitrobenzene (12.0 g, 59.6 mmol) and copper(I) iodide (10.0 g, 73.3 mmol) in anh DMF (50 mL) was added K2CO3 (13.0 g, 91.6 mmol) in one portion. The mixture was heated at the reflux temp. with stirring for 18 h and then allowed to cool to room temp. The mixture was then poured into water (200 mL) and extracted with EtOAc (3150 mL). The combined organics were sequentially washed with water (3100 mL) and a saturated NaCl solution (2*100 mL), dried (Na2SO4), and concentrated in vacuo. The resulting oil was purified by flash chromatography (30% EtOAc/70% hexane) to afford the desired product (1.2 g, 13%).
13%	With copper(l) iodide; potassium carbonate; In DMF (N,N-dimethyl-formamide); for 18h;Heating / reflux;	A13g. General Method for Substituted Aniline Formation via Nitroarene Formation Through Nucleophilic Aromatic Substitution, Followed by Reduction; [] Step 1. 3-(5-Methyl-3-pyridinyloxy)-1-nitrobenzene: To a solution of <strong>[42732-49-0]3-hydroxy-5-methylpyridine</strong> (5.0 g, 45.8 mmol), 1-bromo-3-nitrobenzene (12.0 g, 59.6 mmol) and copper(I) iodide (10.0 g, 73.3 mmol) in anh DMF (50 mL) was added K2CO3 (13.0 g, 91.6 mmol) in one portion. The mixture was heated at the reflux temp. with stirring for 18 h and then allowed to cool to room temp. The mixture was then poured into water (200 mL) and extracted with EtOAc (3 x 150 mL). The combined organics were sequentially washed with water (3 x 100 mL) and a saturated NaCl solution (2 x 100 mL), dried (Na2SO4), and concentrated in vacuo . The resulting oil was purified by flash chromatography (30% EtOAc/70% hexane) to afford the desired product (1.2 g, 13%).

13%	With copper(l) iodide; potassium carbonate; In N,N-dimethyl-formamide; for 18h;Heating / reflux;	Step 1. 3-(5-Methyl-3-pyridinyloxy)-1-nitrobenzene: To a solution of <strong>[42732-49-0]3-hydroxy-5-methylpyridine</strong> (5.0 g, 45.8=nmol), 1-bromo-3-nitrobenzene (12.0 g, 59.6 mmol) and copper(I) iodide (10.0 g, 73.3 mmol) in anh DMF (50 mL) was added K2CO3 (13.0 g, 91.6 mmol) in one portion. The mixture was heated at the reflux temp. with stirring for 18 h and then allowed to cool to room temp. The mixture was then poured into water (200mL) and extracted with EtOAc (3×150 mL). The combined organics were sequentially washed with water (3×100 mL) and a saturated NaCl solution (2×100 mL), dried (Na2SO4), and concentrated in vacuo . The resulting oil was purified by flash chromatography (30% EtOAc/70% hexane) to afford the desired product (1.2 g, 13%).
13%	With copper(l) iodide; potassium carbonate; In N,N-dimethyl-formamide; for 18h;Reflux;	Step 1. 3-(5-Methyl-3-pyridinyloxy)-1-nitrobenzene To a solution of <strong>[42732-49-0]3-hydroxy-5-methylpyridine</strong> (5.0 g, 45.8 mmol), 1-bromo-3-nitrobenzene (12.0 g, 59.6 mmol) and copper(I) iodide (10.0 g, 73.3 mmol) in anh DMF (50 mL) was added K2CO3 (13.0 g, 91.6 mmol) in one portion. The mixture was heated at the reflux temp. with stirring for 18 h and then allowed to cool to room temp. The mixture was then poured into water (200 mL) and extracted with EtOAc (3150 mL). The combined organics were sequentially washed with water (3100 mL) and a saturated NaCl solution (2*100 mL), dried (Na2SO4), and concentrated in vacuo. The resulting oil was purified by flash chromatography (30% EtOAc/70% hexane) to afford the desired product (1.2 g, 13%).

Reference： [1]Patent: US2002/65296,2002,A1
[2]Patent: US2004/102636,2004,A1
[3]Patent: EP1042305,2005,B1 .Location in patent: Page/Page column 30-31
[4]Patent: US2003/207914,2003,A1 .Location in patent: Page/Page column 10
[5]Patent: US2012/46290,2012,A1 .Location in patent: Page/Page column 19

20
[ 42732-49-0 ]
[ 358-23-6 ]
5-methyl-3-pyridinyl trifluoromethanesulfonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%	With triethylamine; In dichloromethane; at 0 - 20℃; for 1h;	Intermediate 4: 5-methyl-3-pvridinvl trifluoromethanesulfonateNIn a two-necked round bottomed flask, under nitrogen atmosphere, <strong>[42732-49-0]3-hydroxy-5-methylpyridine</strong> (500 mg, 4.58 mmol) was suspended in 10 ml of dry methylene chloride. Triethylamine was added (2.5 ml, 18.32 mmol, 4 eq.) and the resulting solution cooled to 0C. A solution of triflic anhydride (1.15 ml, 6.87 mmol, 1.5 eq) in 10 ml of dry methylene chloride was then added dropwise. The solution turned purple. After the end of the addition the mixture was stirred keeping the temperature at 0 C for 1h and then allowed to warm to room temperature. The solvent was removed under vacuum. The crude oil obtained was taken up in a small quantity of DCM and loaded on a 25 g Silica cartridge (1ST). The column was washed with pure cyclohexane and the product collected with a cyclohexane/AcOEt 9/1 mixture. The product was obtained in two fractions: a pure one (orange liquid, 260 mg) and a less pure one (orange liquid, 372 mg, additional small spots in TLC and slight aliphatic impurities in the 1H-NMR). Total -2.6 mmol, 57 % yield.Mass Spectrum (ES): Found 242 (MH+). C7H6F3NO3S requires 241. 1H-NMR (400MHz, CDCI3): 6 2.44 (3H, s), 7.46 (1H, s), 8.43 (1H, s), 8.50 (1H, s)
57%	With triethylamine; In dichloromethane; at 0℃; for 1h;	In a two-necked round bottomed flask, under nitrogen atmosphere, <strong>[42732-49-0]3-hydroxy-5-methylpyridine</strong> (500 mg, 4.58 mmol) was suspended in 10 ml of dry methylene chloride. Triethylamine was added (2.5 ml, 18.32 mmol, 4 eq.) and the resulting solution cooled to 0 C. A solution of triflic anhydride (1.15 ml, 6.87 mmol, 1.5 eq) in 10 ml of dry methylene chloride was then added dropwise. The solution turned purple. After the end of the addition the mixture was stirred keeping the temperature at 0 C for 1 h and then allowed to warm to room temperature. The solvent was removed under vacuum. The crude oil obtained was taken up in a small quantity of DCM and loaded on a 25 g Silica cartridge (IST). The column was washed with pure cyclohexane and the product collected with a cyclohexane/AcOEt 9/1 mixture. The product was obtained in two fractions: a pure one (orange liquid, 260 mg) and a less pure one (orange liquid, 372 mg, additional small spots in TLC and slight aliphatic impurities in the 1H-NMR). Total 2.6 mmol, 57% yield.Mass Spectrum (ES): Found 242 (MH+). C7H6F3NO3S requires 241. 1H-NMR (400 MHz, CDCl3): delta 2.44 (3H, s), 7.46 (1H, s), 8.43 (1H, s), 8.50 (1H, s)

Reference： [1]Patent: WO2006/15828,2006,A1 .Location in patent: Page/Page column 27-28
[2]Patent: US2008/194648,2008,A1 .Location in patent: Page/Page column 12

21
[ 42732-49-0 ]
[ 1355059-13-0 ]
[ 1355059-20-9 ]

Reference： [1]Patent: WO2012/4722,2012,A1

22
[ 42732-49-0 ]
[ 1355059-13-0 ]
C₂₇H₂₇ClN₂O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Method B: To a solution of <strong>[42732-49-0]3-hydroxy-5-methylpyridine</strong> (12 mg, 0.10 mmol, 1.0 eq.) in DMF (1.0 mL), 60% sodium hydride in mineral oil (4.4 mg, 0.1 1 mmol, 1.1 eq.) was added. The mixture was stirred at r.t. for 10 min. A solution of (+/-)-{2-[2-(2-bromo-acetyl)-1 , 2,3,4- tetrahydro-isoquinolin-1-yl]-4-chloro-phenoxy}-acetic acid ethyl ester (47 mg, 0.10 mmol, 1 .0 eq.) in DMF (0.3 mL) was added and the reaction mixture was stirred at r.t. for 4 hours. 1 M aq. NaOH soln. (1 .0 mL) was added. The solution was stirred at r.t. for 30 min. The reaction mixture was acidified with 2M aq. HCI soln. (1 .0 mL) and concentrated in vacuo. The residue, redissolved in DMF (1 .2 mL), was purified by prep. HPLC (column : Atlantis, 19x50 mm, 5 urn, UV/MS, acidic conditions) to give the desired acid.

Reference： [1]Patent: WO2012/4722,2012,A1 .Location in patent: Page/Page column 168-169

23
[ 42732-49-0 ]
[ 585-79-5 ]
[ 229003-18-3 ]

Reference： [1]Patent: US2012/46290,2012,A1

24
[ 42732-49-0 ]
[ 20098-48-0 ]
C₁₂H₈Cl₂N₂O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate; In N,N-dimethyl-formamide; at 25 - 70℃;	General procedure: A 4-halonitrobenzene (1.0 equiv), a hydroxyarene, and Cs2CO3 (1.1 equiv) were combined in DMF and the resulting heterogeneous mixture was stirred vigorously at 25-70 C until all 4-halonitrobenzene was consumed (2-24 h). The reaction mixture was diluted with H2O and was adjusted to pH 5 with 2 N HCl (aq). The solution was extracted three times with EtOAc, and the organic layers were combined, washed once with brine solution, dried over MgSO4, filtered and concentrated in vacuo to furnish the desired diaryl ether that was used directly without further purification.

Reference： [1]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 979 - 992

25
[ 42732-49-0 ]
C₁₂H₁₀Cl₂N₂O [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 979 - 992

26
[ 42732-49-0 ]
[ 1422348-19-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 979 - 992

27
[ 42732-49-0 ]
8-bromo-7-[(4-chlorophenyl)methyl]-1-(3-hydroxypropyl)-3-methyl-2,3,6,7- tetrahydro-1H-purine-2,6-dione [ No CAS ]
7-(4-chlorobenzyl)-1-(3-hydroxypropyl)-3-methyl-8-(5-methylpyridin-3-yloxy)-1H-purine-2,6(3H,7H)-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
48.8%	With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 12h;	Example 88 7-(4-chlorobenzyl)-l -(3-hydroxypropyl)-3-methyl-8-(5-methylpyridin-3-yloxy)- 1 H-purine-2,6(3H,7H)-dione The title compound was prepared using the method of example 55. White solid, 40 mg, 48.8% yield: 'H-NMR (DMSO-^) 5 8.45-8.44(d, 1H), 8.36(s, 1H), 7.65(s,lH), 7.46-7.41 (m, 4H), 5.44(s, 2H), 4.50-4.47(t, 1H), 3.94-3.91(t, 2H), 3.46-3.40(m, 2H), 3.28(s, 3H), 2.34(s, 3H), 1.73- 1.66(m, 2H). LCMS retention time 2.259 min; LCMS MH+ 456

Reference： [1]Patent: WO2014/143799,2014,A2 .Location in patent: Page/Page column 508; 509; 539

28
[ 42732-49-0 ]
8-chloro-7-(4-chlorobenzyl)-3-ethyl-1-(3-hydroxypropyl)-1H-purine-2,6(3H,7H)-dione [ No CAS ]
7-(4-chlorobenzyl)-3-ethyl-1-(3-hydroxypropyl)-8-((5-methylpyridin-3-yl)oxy)-1H-purine-2,6(3H,7H)-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
22.5%	With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 3h;	Example 125 7-(4-chlorobenzyl)-3-ethyl-l -(3-hydroxypropyl)-8-((5-methylpyridin-3-yl)oxy)- 1 H-purine-2,6(3H,7H)-dione To a solution of 8-chloro-7-(4-chlorobenzyl)-3-ethyl-l -(3-hydroxypropyl)-lH-purine- 2,6(3H,7H)-dione (30 mg, 0.08 mmol, intermediate 78) in DMF (2 mL) was added 5- methylpyridin-3-ol (12.36 mg, 0.12 mmol), followed by potassium carbonate (15.66 mg, 0.11 mmol). The reaction was stirred at 80 C for 3 h. The reaction was cooled and partitione between ethyl acetate and water. The organic phase was washed with brine, dried over sodium sulfate, and concentrated to give a crude product, which was purified by preparative HPLC to give 7-(4- chlorobenzyl)-3-ethyl- l-(3-hydroxypropyl)-8-((5-methylpyridin-3-yl)oxy)- l H-purine- 2,6(3H,7H)-dione (8 mg, 22.5 %) as white solid. 'H-NMR (CD3OD) delta 8.35-8.42(d, 2Eta), 7.68(s, 1Eta), 7.38-7.48(m, 4Eta), 5.52(s, 2Eta), 4.01 -4.14(m, 4Eta), 3.61 -3.64(m, 2Eta), 2.43(s, 3Eta), 1.87- 1 .90(m, 2Eta), 1.22-1.26(m, 3Eta). LCMS retention time 2.51 1 min; LCMS MH+ 470.

Reference： [1]Patent: WO2014/143799,2014,A2 .Location in patent: Page/Page column 567; 568

29
[ 42732-49-0 ]
[ 1235406-40-2 ]
[ 76-05-1 ]
3-cyano-4-[(5-methylpyridin-3-yl)oxy]-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide trifluoroacetic acid salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: A 0.1 875M solution in NMP of the compound of formula (Pa) (400 tL, 75 jtmol) was added to the compound of formula (IV) (90 jtmol) followed by cesium carbonate (47 mg, 150 tmol). The reaction mixture was shaken and heated to 150 C. for 3 hours before cooling and concentrating in vacuo. The residue was dissolved in DM50 (1 mL) and purified using preparative HPLC as described below to afford the desired compound of formula (Ia). Preparative HPLC/LCMS Conditions:Mobile phase A:0.05% TFA in water; Mobile phaseB: MeCN Column: Welch XB-C18 (2.1x50 mm, 5 u)The compounds of the Examples in the table belowwere prepared from 3-cyano-4-fluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide (W02012004743) and the appropriUSate phenol according to Library Protocol 4.

Reference： [1]Patent: US2014/315933,2014,A1 .Location in patent: Paragraph 0425; 0426; 0427; 0428

30
[ 42732-49-0 ]
1-(5-bromo-4-fluoropyridin-2-yl)-3-methylurea [ No CAS ]
1-(5-bromo-4-((5-methylpyridin-3-yl)oxy)pyridin-2-yl)-3-methylurea [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2016,vol. 7,p. 714 - 718
[2]ACS Medicinal Chemistry Letters,2016,vol. 7,p. 666 - 670

31
[ 42732-49-0 ]
1-(5-(trans-2-(2-hydroxypropan-2-yl)cyclopropyl)-4-((5-methylpyridin-3-yl)oxy)pyridin-2-yl)-3-methylurea [ No CAS ]
1-(5-(trans-2-(2-hydroxypropan-2-yl)cyclopropyl)-4-((5-methylpyridin-3-yl)oxy)pyridin-2-yl)-3-methylurea [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2016,vol. 7,p. 666 - 670

32
[ 42732-49-0 ]
1-(5-(trans-2-(hydroxymethyl)cyclopropyl)-4-((5-methylpyridin-3-yl)oxy)pyridin-2-yl)-3-methylurea [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2016,vol. 7,p. 666 - 670

33
[ 42732-49-0 ]
1-(5-(trans-2-(2-hydroxypropan-2-yl)cyclopropyl)-4-((5-methylpyridin-3-yl)oxy)pyridin-2-yl)-3-methylurea [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2016,vol. 7,p. 666 - 670

34
[ 42732-49-0 ]
trans-ethyl 2-(4-fluoro-6-(3-methylureido)pyridin-3-yl)cyclopropanecarboxylate [ No CAS ]
trans-ethyl 2-(4-((5-methylpyridin-3-yl)oxy)-6-(3-methylureido)pyridin-3-yl)cyclopropanecarboxylate [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2016,vol. 7,p. 666 - 670

35
[ 42732-49-0 ]
1-(2-fluoro-4-iodophenyl)-3-(4-methoxybenzyl)-8-methyl-2,4,7-trioxo-pyrido[2,3-d]pyrimidin-5-yl trifluoromethanesulfonate [ No CAS ]
5-((5-methylpyridin-3-yl)oxy)-1-(2-fluoro-4-iodophenyl)-3-(4-methoxybenzyl)-8-methylpyrido[2,3-d]pyrimidine-2,4,7(1H,3H,8H)-trione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		5-methyl-3-hydroxy-pyridine (43 mg, 0.40 mmol) was dissolved in 5 mL of tetrahydrofuran, followed by addition of sodium hydride (16 mg, 0.40 mmol). After stirring for 1 hour, the reaction solution was added with 1-(2-fluoro-4-iodophenyl)-3-(4-methoxybenzyl)-8-methyl-2,4,7-trioxo-pyrido[2,3-d]pyr imidin-5-yl trifluoromethanesulfonate 1j (136 mg, 0.20 mmol), and stirred for 12 hours. The reaction solution was concentrated under reduced pressure to obtain the crude title compound 5-((5-methylpyridin-3-yl)oxy)-1-(2-fluoro-4-iodophenyl)-3-(4-methoxybenzyl)-8-methylpyrido[2,3-d]pyrimidine-2,4,7(1H,3H,8H)-trione 30a (128 mg, pale yellow liquid), which was used directly in the next step without further purification.

Reference： [1]Patent: EP3061747,2016,A1 .Location in patent: Paragraph 0223

36
[ 42732-49-0 ]
1-amino-3-(methoxymethoxy)-5-methylpyridin-1-ium 2,4,6-trimethylbenzenesulfonate [ No CAS ]

Reference： [1]Patent: WO2016/133793,2016,A1

37
[ 42732-49-0 ]
[ 107-30-2 ]
3-(methoxymethoxy)-5-methylpyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of <strong>[42732-49-0]5-methylpyridin-3-ol</strong> (2 g, 18.33 mmol) in DMF (10 ml) was added potassium tert-butoxide (2.2 g, 19.61 mmol) at 0C. It was stirred for 5 min and to the mixture was added a solution of MOM-Cl (1.46 ml, 19.22 mmol) in THF (10.00 ml) by a syringe pump over 1 h. It was stirred for another 1 h after the addition. The reaction was quenched with water (100 mL) and the mixture was extracted with ethyl acetate (3x50 mL). The combined organic layers were washed with water (50 mL), brine (50 mL), dried over sodium sulfate, filtered and concentrated. The residue was purified by ISCO (80 g, 0-50% ethyl acetate in hexane) to give 3- (methoxymethoxy)-5-methylpyridine. LCMS calc. = 154.09; found = 154.04 (M+H)+.

Reference： [1]Patent: WO2016/133793,2016,A1 .Location in patent: Page/Page column 30; 68

38
[ 42732-49-0 ]
(2-(1-ethyl-1H-indol-2-yl)-1-methyl-1H-benzo[d]imidazol-5-yl)(3-hydroxy-5-methylpiperidin-1-yl)methanone [ No CAS ]

Reference： [1]Patent: WO2016/185279,2016,A1

39
[ 42732-49-0 ]
1-(2-(1-ethyl-1H-indol-2-yl)-1-methyl-1H-benzo[d]imidazole-5-carbonyl)-5-methylpiperidin-3-yl methanesulfonate [ No CAS ]

Reference： [1]Patent: WO2016/185279,2016,A1

40
[ 42732-49-0 ]
(3-azido-5-methylpiperidin-1-yl)(2-(1-ethyl-1H-indol-2-yl)-1-methyl-1H-benzo[d]imidazol-5-yl)methanone [ No CAS ]

Reference： [1]Patent: WO2016/185279,2016,A1

41
[ 42732-49-0 ]
trans-(3-amino-5-methylpiperidin-1-yl)(2-(1-ethyl-1H-indol-2-yl)-1-methyl-1H-benzo[d]imidazol-5-yl)methanone hydrochloride [ No CAS ]
trans-(3-amino-5-methylpiperidin-1-yl)(2-(1-ethyl-1H-indol-2-yl)-1-methyl-1H-benzo[d]imidazol-5-yl)methanone hydrochloride [ No CAS ]

Reference： [1]Patent: WO2016/185279,2016,A1

42
[ 42732-49-0 ]
[ 33469-64-6 ]

Yield	Reaction Conditions	Operation in experiment
86%	With palladium on activated charcoal; hydrogen; acetic acid; at 100℃; under 75007.5 Torr;	5-Methylpyridin-3-ol (507 mg, 4.65 mmol, commercially available from, for example, Alfa Aesar) in acetic acid (30 mL) (approx 0.15M solution) was hydrogenated through the H-cube using Pd/C cat-cart (49.4 mg, 0.465 mmol) as the catalyst and conditions of 100 C and 100 bar pressure and recycled constantly at lmL minute overnight. Solvent was removed and the residue loaded onto a 10 g SCX-2 cartridge, washing with methanol and then eluting with 2M methanolic ammonia. The solvent was removed and the residue dried under high vacuum overnight to afford the title compound as a yellow oil (458 mg, 86%.)LCMS (Method B): Rt=0.38 min, MH+=116.0.
68%	With platinum(IV) oxide; rhodium contaminated with carbon; hydrogen; acetic acid; In methanol; at 20 - 60℃; under 22801.5 Torr; for 16h;	At room temperature, <strong>[42732-49-0]5-methylpyridin-3-ol</strong> (9.50 g, 87.06 mmol), Pt02 (2767 mg, 12.19 mmol) and Rh/C (2866 mg, 27.86 mmol) were added to a 500 mL pressure tank, followed by the addition of AcOH (200 mL). The tank was vacuumed and flushed with hydrogen. The reaction mixture was hydrogenated for 16 h at 60 C under 30 atm hydrogen atmosphere. When the reaction was done, the reaction mixture was filtered through a Celite pad and the filtrate was concentrated under reduced pressure to yield the title compound as brown oil (6.80 g, 68 %). MS: 1 16 [M+H]+.

Reference： [1]Patent: WO2016/185279,2016,A1 .Location in patent: Page/Page column 96
[2]Patent: WO2020/25517,2020,A1 .Location in patent: Paragraph 00233; 00265

43
[ 42732-49-0 ]
3-[(2,6-difluorobenzyl)oxy]-5-methyl-2-nitropyridine [ No CAS ]

Reference： [1]Patent: US2017/57954,2017,A1
[2]Patent: US2017/217954,2017,A1

44
[ 42732-49-0 ]
3-[(2,6-difluorobenzyl)oxy]-5-methylpyridine-2-amine [ No CAS ]

Reference： [1]Patent: US2017/57954,2017,A1
[2]Patent: US2017/217954,2017,A1

45
[ 42732-49-0 ]
ethyl 8-[(2,6-difluorobenzyl)oxy]-2-ethyl-6-methylimidazo[1,2-a]pyridine-3-carboxylate [ No CAS ]

Reference： [1]Patent: US2017/57954,2017,A1
[2]Patent: US2017/217954,2017,A1

46
[ 42732-49-0 ]
8-[(2,6-difluorobenzyl)oxy]-2-ethyl-6-methylimidazo[1,2-a]pyridine-3-carboxylic acid [ No CAS ]

Reference： [1]Patent: US2017/57954,2017,A1
[2]Patent: US2017/217954,2017,A1

47
[ 42732-49-0 ]
ethyl 8-[(2,6-difluorobenzyl)oxy]-6-methyl-2-propylimidazo[1,2-a]pyridine-3-carboxylate [ No CAS ]

Reference： [1]Patent: US2017/57954,2017,A1
[2]Patent: US2017/217954,2017,A1

48
[ 42732-49-0 ]
8-[(2,6-difluorobenzyl)oxy]-6-methyl-2-propylimidazo[1,2-a]pyridine-3-carboxylic acid [ No CAS ]

Reference： [1]Patent: US2017/57954,2017,A1
[2]Patent: US2017/217954,2017,A1

49
[ 42732-49-0 ]
[ 364757-81-3 ]
4,5,6,7-tetrahydro-3-[(5-methylpyridin-3-yl)oxy]-4-oxobenzo[c]thiophene-1-carboxylic acid ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	With potassium carbonate; In ethyl acetate; toluene; at 80℃; for 16h;Sealed tube;	General procedure: In a sealed tube, a solution of 35 (2.0 g, 6.62 mmol) in EtOAc (5 mL)/toluene (5 mL) were added methanol (0.30 mL, 7.28 mmol) and K2CO3 (1.37 g, 9.93 mmol) at rt. The resulting mixture was stirred at 80 C for 16 h. The reaction mixture was diluted with water (20 mL) and extracted with EtOAc twice. The organic layers were washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, eluted with 15% EtOAc in hexane) to yield the title compound.

Reference： [1]Bioorganic and Medicinal Chemistry,2017,vol. 25,p. 2336 - 2350

50
[ 42732-49-0 ]
2-iodo-5-methylpyridin-3-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	With iodine; sodium carbonate; potassium iodide; In water; at 20℃; for 2.2h;Inert atmosphere;	2-iodo-<strong>[42732-49-0]5-methylpyridin-3-ol</strong> (0299) To a solution of sodium carbonate (7.0 g, 65.95 mmol) in water (200 mL) was added <strong>[42732-49-0]5-methylpyridin-3-ol</strong> (3.42 g, 31.34 mmol) at room temperature. To the reaction mixture was added a solution of potassium iodide (5.21 g, 31.36 mmol) and iodine (7.95 g, 31.33 mmol) in water (200 mL) dropwise over 1.2 h period. The resulting solution was stirred for 2 h at room temperature and then the pH value of the reaction mixture was adjusted to 1 with hydrochloric acid solution (1 M). The solid that formed was removed by filtration. The pH value of the filtrate was adjusted to 9 with saturated sodium carbonate solution. The resulting solution was extracted with ethyl acetate (200 mL×3) and the organic phases were combined, washed with brine and dried over sodium sulfate. The solvent was removed under reduced pressure to yield 2-iodo-<strong>[42732-49-0]5-methylpyridin-3-ol</strong> as yellow solid (5.0 g, 68%). MS: m/z=236.0 [M+H]+.

Reference： [1]Patent: US2016/376283,2016,A1 .Location in patent: Paragraph 0298; 0299

51
[ 42732-49-0 ]
6-methyl-2-(trimethylsilyl)furo[3,2-b]pyridine [ No CAS ]

Reference： [1]Patent: US2016/376283,2016,A1

52
[ 42732-49-0 ]
6-methyl-2-(trimethylsilyl)furo[3,2-b]pyridine 4-oxide [ No CAS ]

Reference： [1]Patent: US2016/376283,2016,A1

53
[ 42732-49-0 ]
7-chloro-6-methyl-2-(trimethylsilyl)furo[3,2-b]pyridine [ No CAS ]

Reference： [1]Patent: US2016/376283,2016,A1

54
[ 42732-49-0 ]
7-chloro-2-iodo-6-methylfuro[3,2-b]pyridine [ No CAS ]

Reference： [1]Patent: US2016/376283,2016,A1

55
[ 66527-53-5 ]
[ 42732-49-0 ]

Reference： [1]Chemical Communications,2017,vol. 53,p. 6417 - 6420

56
2-methyl-1-(1-tosyl-1H-1,2,3-triazol-4-yl)allyl acetate [ No CAS ]
[ 42732-49-0 ]

Reference： [1]Chemical Communications,2017,vol. 53,p. 6417 - 6420

57
C₈H₁₀O₂ [ No CAS ]
[ 42732-49-0 ]

Reference： [1]Chemical Communications,2017,vol. 53,p. 6417 - 6420

58
[ 1572-63-0 ]
[ 42732-49-0 ]

Reference： [1]Chemical Communications,2017,vol. 53,p. 6417 - 6420

59
[ 42732-49-0 ]
2-(4-hydroxypiperidin-1-yl)-3-methyl-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one [ No CAS ]
3-methyl-2-(4-((5-methylpyridin-3-yl)oxy)piperidin-1-yl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With di-tert-butyl (E)-azodicarboxylate; triphenylphosphine; In toluene; at 100℃; for 16h;	To a solution of 2-(4-hydroxypiperidin-1-yl)-3-methyl-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one (30 mg, 0.121 mmol, intermediate H1), <strong>[42732-49-0]5-methylpyridin-3-ol</strong> (13.24 mg, 0.121 mmol) and triphenylphosphine (47.7 mg, 0.182 mmol) in toluene (1 mL) was added (E)-di-tert-butyl diazene-1,2-dicarboxylate (41.9 mg, 0.182 mmol). The reaction mixture was stirred at 100 C. for 16 h. The solvent was evaporated under reduced pressure and was directly purified by reverse phase HPLC (ACN/water with 0.1% TFA modifier) to yield the title compound. MS: 339 (M+1). 1H NMR (400 MHz, methanol-d4): delta 8.49 (1H, s), 8.32 (1H, s), 8.17 (1H, s), 7.82 (1H, s), 4.91-4.92 (1H, m), 4.34 (2H, s), 3.59-3.63 (2H, m), 3.25-3.29 (2H, m), 2.56 (3H, s), 2.40 (3H, s), 2.22-2.26 (2H, m), 1.97-2.06 (2H, m).

Reference： [1]Patent: US2017/183342,2017,A1 .Location in patent: Paragraph 0429-430

60
[ 42732-49-0 ]
[ 24424-99-5 ]
tert-butyl (3S,5R)-rel-3-hydroxy-5-methylpiperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
49%		A saturated solution of HCI in EtOAc (80 mL) was added to a solution of 5- methyl-3-pyridinol (10.0 g, 91 .6 mmol) in EtOAc (15 mL) and MeOH (5 mL) and the mixture stirred for 4 hr at 23 C. The resulting solid was filtered off and washed with EtOAc and dried under vacuum. The solid was dissolved in acetic acid (50 ml_), 10% Pt02 (1 .0 g) was added and the resulting reaction mixture was hydrogenated in a Parr autoclave (pressure 200 psi) for 16 hrs at 50 C. The cooled mixture was filtered through Celite and the filtrate was concentrated to afford a brown gum, 5.0 g. Boc-anhydride (10.79 ml_, 49.45 mmol) was added drop wise to an ice-cooled stirred solution of the gum in 50% EtOAc/water (100 ml) and Na2C03 (10.48 g, 98.89 mmol) and the resulting reaction was stirred at rt for 15 hrs. The mixture was extracted with EtOAc, the combined organic extracts washed with brine, dried (Na2SO4) and concentrated in vacuo. The crude product was purified by column chromatography on silica gel eluting with EtOAc: Hexane (20:80) to afford the title compound as a yellow liquid, 3.5 g, 49%. 1H NMR (400 MHz, DMSO-d6): delta 0.80-0.91 (m, 4H), 1 .38 (s, 9H), 1 .44-1 .47 (m, 1 H), 1 .86-1 .90 (m, 1 H), 2.05-2.32 (m, 2H), 3.28-3.34 (m, 1 H), 3.75-3.86 (m, 1 H), 3.94-4.03 (m, 1 H), 4.91 (d, 1 H).

Reference： [1]Patent: WO2018/11681,2018,A1 .Location in patent: Page/Page column 110-111

61
[ 42732-49-0 ]
(3R,5S)-rel-5-methylpiperidin-3-ol hydrochloride [ No CAS ]

Reference： [1]Patent: WO2018/11681,2018,A1

62
[ 42732-49-0 ]
[ 89031-84-5 ]
C₁₅H₂₇NO₂Si [ No CAS ]

Reference： [1]Patent: WO2019/28309,2019,A1 .Location in patent: Page/Page column 36; 41

63
[ 42732-49-0 ]
[ 89031-84-5 ]
C₂₀H₃₄N₂O₂Si [ No CAS ]

Reference： [1]Patent: WO2019/28309,2019,A1

64
[ 42732-49-0 ]
8-[cis-3-methyl-5-(1H-1,2,3-triazol-1-yl)piperidin-1-yl]quinoxaline-5-carbonitrile [ No CAS ]