105250-16-6|(2-Methylpyridin-4-yl)methanol| Ambeed

Structure of 105250-16-6

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Quality Control of [ 105250-16-6 ] Purity: 98% SDS Specification

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Product Details of [ 105250-16-6 ]

CAS No. :	105250-16-6
Formula :	C₇H₉NO
M.W :	123.15
SMILES Code :	OCC1=CC(C)=NC=C1
MDL No. :	MFCD08062415
InChI Key :	WCHFSXVRRCEWJL-UHFFFAOYSA-N
Pubchem ID :	9942144

Safety of [ 105250-16-6 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H332-H335
Precautionary Statements:	P261-P280-P305+P351+P338

Computational Chemistry of [ 105250-16-6 ] Show Less

Physicochemical Properties

Num. heavy atoms	9
Num. arom. heavy atoms	6
Fraction Csp3	0.29
Num. rotatable bonds	1
Num. H-bond acceptors	2.0
Num. H-bond donors	1.0
Molar Refractivity	35.33
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	33.12 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.53
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	0.37
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	0.73
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.	0.22
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	1.65
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	0.9

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-1.26
Solubility	6.71 mg/ml ; 0.0545 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-0.63
Solubility	28.8 mg/ml ; 0.234 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	-2.2
Solubility	0.784 mg/ml ; 0.00637 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.	-6.79 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)	1.11

Application In Synthesis of [ 105250-16-6 ]

* 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 [ 105250-16-6 ]

[ 105250-16-6 ] Synthesis Path-Downstream 1~35

1
[ 105250-16-6 ]
[ 75523-42-1 ]

Yield	Reaction Conditions	Operation in experiment
100%		Example 196 5-[(2-Chlorophenyl)acetylamino]-3-(4-fluorophenyl)-4-[4-(2-methylpyridyl)]isoxazole a) 4-Chloromethyl-2-methylpyridine; Into 100 mL of methylene chloride solution containing 2. 1-6 g of 4-(2-methylpyridyl)methanol (cf. PCT International Publication WO98/2120 Pamphlet), 23 mL of thionyl chloride was dropped at room temperature, followed by 20 hours' stirring at room temperature. The solvent was distilled off from the reaction solution under reduced pressure, and the residue was extracted with methylene chloride, after addition of saturated aqueous NaHCO3 solution. The methylene chloride extract was dried over anhydrous magnesium sulfate, and from which the solvent was distilled off under reduced pressure to provide 2.46 g (yield: 100%) of brown crystalline title compound. 1H-NMR(CDCl3)delta:8.45(d,J=5.0Hz,1H),7.31(s,1H), 7.25(d,J=5.0Hz,1H),4.74(s,2H),2.48(s,3H) Mass,m/e:141 (M+,base)
		Reference Example 47 3-(3-(4-(2-Methyl-pyridin-4-ylmethoxy)-benzyl)-isoxazol-5-yl)-pyridin-2-ylamine; (2-Methyl-pyridin-4-yl)-methanol (40 mg, 0.33 mmol) described in Manufacturing Example 47-1-1, thionyl chloride (0.047 ml, 0.65 mmol) and methylene chloride (4.0 ml) were stirred for 5 minutes at 60 C. Sodium bicarbonate solution and ethyl acetate were added to separate the reaction solution, and the ethyl acetate layer was dried over sodium sulfate. The solvent was evaporated under a reduced pressure to obtain 4chloromethyl-2-methyl-pyridine as a crude product.2 N Sodium hydroxide (0.16 ml, 0.32 mmol) and methanol (1.0 ml) were added to dissolve 4-(5-(2-amino-pyridin-3-yl)isoxazol-3-ylmethyl)-phenol (87 mg, 0.33 mmol) described in Manufacturing Example 5-1-1, and methanol was evaporated under a reduced pressure. A solution of the aforementioned 4-chloromethyl-2-methyl-pyridine dissolved in dimethylformamide (1 ml) was added to the residue and stirred for 10 minutes at 60 C. Water and ethyl acetate were added to separate the reaction solution, the resulting ethyl acetate layer was concentrated under a reduced pressure, and the residue was purified by silica gel column chromatography (heptane:ethyl acetate=1:3) to obtain the title compound (47 mg, 39%).1H-NMR Spectrum (DMSO-d6) delta (ppm): 2.47 (3H, s), 3.96 (2H, s), 5.11 (2H, s), 6.25 (2H, brs), 6.68 (1H, dd, J=4.8, 8.0 Hz), 6.79 (1H, s), 6.97 (2H, d, J=8.8 Hz), 7.20 (1H, d, J=5.2 Hz), 7.25 (2H, d, J=8.8 Hz), 7.29 (1H, s), 7.86 (1H, dd, J=2.0, 8.0 Hz), 8.08 (1H, dd, J=2.0, 4.8 Hz), 8.42 (1H, d, J=5.2 Hz).
		(2-Methyl-pyridin-4-yl)-methanol (40 mg, 0.33 mmol) described in Manufacturing Example 47-1-1, thionyl chloride (0.047 ml, 0.65 mmol) and methylene chloride (4.0 ml) were stirred for 5 minutes at 60 C. Sodium bicarbonate solution and ethyl acetate were added to separate the reaction solution, and the ethyl acetate layer was dried over sodium sulfate. The solvent was evaporated under a reduced pressure to obtain 4-chloromethyl-2-methyl-pyridine as a crude product. 2 N Sodium hydroxide (0.16 ml, 0.32 mmol) and methanol (1.0 ml) were added to dissolve 4-(5-(2-amino-pyridin-3-yl)isoxazol-3-ylmethyl)-phenol (87 mg, 0.33 mmol) described in Manufacturing Example 5-1-1, and methanol was evaporated under a reduced pressure. A solution of the aforementioned 4-chloromethyl-2-methyl-pyridine dissolved in dimethylformamide (1 ml) was added to the residue and stirred for 10 minutes at 60 C. Water and ethyl acetate were added to separate the reaction solution, the resulting ethyl acetate layer was concentrated under a reduced pressure, and the residue was purified by silica gel column chromatography (heptane:ethyl acetate=1:3) to obtain the title compound (47 mg, 39%). 1H-NMR Spectrum (DMSO-d6) delta (ppm): 2.47 (3H, s), 3.96 (2H, s), 5.11 (2H, s), 6.25 (2H, brs), 6.68 (1H, dd, J=4.8, 8.0 Hz), 6.79 (1H, s), 6.97 (2H, d, J=8.8 Hz), 7.20 (1H, d, J=5.2 Hz), 7.25 (2H, d, J=8.8 Hz), 7.29 (1H, s), 7.86 (1H, dd, J=2.0, 8.0 Hz), 8.08 (1H, dd, J=2.0, 4.8 Hz), 8.42 (1H, d, J=5.2 Hz).

400 mg

With thionyl chloride; In dichloromethane; at 27℃; for 16h;

To a solution of <strong>[105250-16-6](2-methylpyridin-4-yl)methanol</strong> (500 mg, 4.06 mmol, commercial source: Combi-Blocks) in dichloromethane (20 mL), thionyl chloride (0.45 mL, 1 .5 mmol) was added at 0 C. The reaction mixture was allowed to 27 C and stirred for 16 h. On completion, the reaction mixture was concentrated under reduced pressure. The residue was neutralized (pH 7) with saturated sodium bicarbonate solution (10 mL) and extracted with ethyl acetate (2x50 mL). The organic layer was dried over Na2S04, filtered and the filtrate was evaporated under reduced pressure to afford 4-(chloromethyl)-2-methylpyridine (400 mg) as an off-white solid. NMR (400 MHz, CDCI3) delta 8.49 (d, J = 5.1 Hz, 1 H), 7.18 (s, 1 H), 7.1 1 (dd, J = 5.2, 1.6 Hz, 1 H), 4.50 (s, 2H), 2.57 (s, 3H). MS m/z [M+H]+= 142.0.

References: [1]Patent: EP2036905,2009,A1 .Location in patent: Page/Page column 49.
[2]Pharmaceutical Bulletin,1955,vol. 3,p. 413,415.
Yakugaku Zasshi,1956,vol. 76,p. 900.
Chem.Abstr.,1957,p. 2770.
[3]Patent: US2009/82403,2009,A1 .Location in patent: Page/Page column 96.
[4]Patent: US2007/105904,2007,A1 .Location in patent: Page/Page column 95.
[5]Patent: WO2019/34729,2019,A1 .Location in patent: Page/Page column 37; 38.

2
[ 1122-45-8 ]
[ 108-24-7 ]
[ 42508-74-7 ]
[ 105250-16-6 ]
[ 27296-77-1 ]

References: [1]Pharmaceutical Bulletin,1955,vol. 3,p. 413,415.
Yakugaku Zasshi,1956,vol. 76,p. 900.
Chem.Abstr.,1957,p. 2770.

3
[ 1122-45-8 ]
[ 105250-16-6 ]

References: [1]Pharmaceutical Bulletin,1955,vol. 3,p. 413,415.
Yakugaku Zasshi,1956,vol. 76,p. 900.
Chem.Abstr.,1957,p. 2770.

4
[ 67-56-1 ]
C₇H₁₀NO⁽¹⁺⁾*BF₄^(1-) [ No CAS ]
[ 1122-71-0 ]
[ 105250-16-6 ]

References: [1]Synthetic Communications,1989,vol. 19,p. 317 - 326.

5
[ 105250-16-6 ]
4-(bromomethyl)-2-methylpyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dibromo sulfoxide; In dichloromethane; for 1h;	To a solution of (2-methylpyridin-4-yl)-methanol (0.510 g, 4.14 mmol) in 8 mL ofdichloromethane was added thionyl bromide (1.03 g, 4.97 mmol) dropwise. After 1 h, the reaction was quenched with saturated aqueous ammonium chloride. The organic solution was washed 2x with water, dried over sodium sulfate, filtered, and concentrated in vacuo to provide 4-(bromomethyl)-2-methylpyridine that gave proton NMR spectra consistent with theory and a a mass ion (ES+) of 188.0 (8iBr) for [M+H .

References: [1]Journal of Medicinal Chemistry,1995,vol. 38,p. 1892 - 1903.
[2]Patent: WO2011/75371,2011,A1 .Location in patent: Page/Page column 53.

6
[ 105250-16-6 ]
[ 18162-48-6 ]
[ 1006302-00-6 ]

Yield	Reaction Conditions	Operation in experiment
90%	With 1H-imidazole; In N,N-dimethyl-formamide; at 20℃;	4-(tert-Butyl-dimethyl-silanyloxymethyl)-2-methyl-pyridine:; 2-methylpyridine methanol (3.39 g, 27.56 mmol) was stirred with imidazole (6.12 g, 90 mmol), and tert-butyldimethylchlorosilane (6.78 g, 45 mmol) in DMF 960 ml) at room temperature for overnight. The mixture was diluted with ether, washed with aqueous saturated sodium bicarbonate, dried with anhydrous magnesium sulfate, filtered, and evaporated in vacuo. The residue was purified by silica gel column chromatography (eluent, ether:hexane (1:2)) to afford 5.9 g (90%) of 4-(tert-butyl-dimethyl-silanyloxymethyl)-2-methyl-pyridine as a colorless oil. 1H NMR (200 MHz, CDCl3) delta0.11 (6H, s), 0.94 (9H, s), (3H, s), 2.52 (3H, s), 4.67 (2H, s), 6.97 (1H, d, J=6.7 Hz), 7.08 (1H, s), 8.10 (1H, d, J=6.7 Hz).
	With 1H-imidazole; In dichloromethane; at 0 - 20℃; for 1h;	(2-Methyl-pyridin-4-yl)-methanol (43.51 g, 354 mmol) was dissolved in CH2C12 (500 mL) and cooled to 0 C. tert-Butyldimethylsilyl chloride (53.32 g, 354 mmol) was added, followed by imidazole (36 g, 531 mmol), and the reaction was warmed to room temperature and stirred for 1 hour. The mixture was filtered through filter paper, and the filtrate was washed 3 times with H20/brine, then dried, filtered, and concentrated to give the title compound.

References: [1]Patent: US2008/70920,2008,A1 .Location in patent: Page/Page column 98.
[2]Bioorganic and Medicinal Chemistry,1997,vol. 5,p. 49 - 64.
[3]Patent: WO2011/38086,2011,A2 .Location in patent: Page/Page column 86.

7
[ 63875-01-4 ]
[ 105250-16-6 ]

References: [1]Synthesis,2002,p. 483 - 486.

8
[ 105250-16-6 ]
[ 5398-44-7 ]
2-chloro-6-(2-methyl-pyridin-4-ylmethoxy)-isonicotinic acid [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 1892 - 1897.

9
[ 105250-16-6 ]
[ 124-63-0 ]
[ 923297-49-8 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In chloroform; at 0℃; for 1.5h;	Example BM; To a stirred solution of 2-chloro-4-pyridinemethanol (123 mg, 1 mmol) in chloroform (10 ml) at 0 C. (ice bath), was added triethylamine (210 mul, 1.5 mmol) and methanesulfonyl chloride (90 mul, 1.2 mmol). After stirring for 1.5 hr., the mixture was diluted with dichloromethane, washed with aqueous saturated sodium bicarbonate solution, dried with anhydrous magnesium sulfate, filtered, and evaporated in vacuo. The residue was further dried in high vacuo and mixed with 3-[3-(5-isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbonyl)-5-methyl-phenyl]-acrylonitrile (323 mg, 1 mmol), anhydrous powdered potassium carbonate (138 mg, 1 mmol), lithium iodide (134 mg, 1 mmol). Anhydrous DMF (5 ml) was then added into the mixture and stirred for overnight at room temperature. The mixture was evaporated in vacuo. The residue was dissolved in methanol-dichloromethane (1:9), filtered through celite pad, and the filtrate was evaporated in vacuo and the residue was purified by silica gel column chromatography (eluent, EA:hexane (1:1)) to afford 186 mg (43%) of a white solid. m.p. 173-174 C.; 1H-NMR (200 MHz, CDCl3/CD3OD) delta 1.09(3H, d, J=6.8 Hz), 1.20 (3H, d, J=6.8 Hz), 2.26 (1H, m), 2.37 (6H, s), 4.54 (1H, d, J=16.6 Hz), 4.89 (1H, d, J=16.6 Hz), 6.02 (1H, d, J=16.6 Hz), 6.81-6.84 (2H, m), 7.38 (1H, d, J=16.6 Hz), 7.51 (1H, s), 7.54 (1H, s), 7.68 (1H, s), 8.18 (1H, dd, J=1.4 Hz, 3.4 Hz); m/z (EI) 428(M+).
	With triethylamine; In dichloromethane; at 0 - 20℃;	The mesylate of <strong>[105250-16-6](2-methylpyridin-4-yl)methanol</strong> (100 mg) was prepared by reaction with methanesulfonyl chloride (1 .1 eq) and triethylamine (2 eq) in DCM at 0 C, with warming to ambient temperature. N-[1 -(Fluoromethyl)cyclopropyl]-3-[(1 -methylpyrazol-4- yl)methyl]-2,4-dioxo-1 1H-quinazoline-6-sulfonamide (100 mg, 0.260 mmol), the crude mesylate (58 mg, 0.286 mmol) and potassium carbonate (43 mg, 0.312 mmol) in DMF was conventionally heated to 70 C for 4 h. Usual work-up afforded the desired product (46 mg, 0.090 mmol, 35%) as a white powder.
	With triethylamine; In ethyl acetate; for 4h;	Alcohol S6 (0.040 g, 0.325 mmol) was added to an oven dried 20mL vial, followed by ethyl acetate (10 mL). Next, mesyl chloride (0.030 mL, 0.390 mmol) was added, followed by NEt3(0.054 mL, 0.390 mmol). The reaction was stirred for 4 h, after which time a sample aliquot was taken from the reaction,dissolved in 1 mL HPLC grade MeCN, and analyzed with LC-MS to confirm the completion of the reaction. The reaction was diluted with EtOAc (50 mL), and washed with water (10 mL) and brine before being condensed, yielding the titlecompound as a light yellow oil. The compound was used directly in the next step of the reaction without further purificationor analysis.

References: [1]Patent: US2008/70920,2008,A1 .Location in patent: Page/Page column 84.
[2]Patent: WO2016/92326,2016,A1 .Location in patent: Paragraph 00778.
[3]Bioorganic and Medicinal Chemistry Letters,2019,vol. 29.

10
[ 55485-90-0 ]
[ 105250-16-6 ]

Yield	Reaction Conditions	Operation in experiment
94%	With methanol; ammonia; water; at 20℃; for 24h;	(2-Methyl-pyridin-4-yl)-methanol:; Acetic acid 2-methyl-pyridin-4-ylmethyl ester (5.1 g, 31 mmol) was stirred with ammonium hydroxide (10 ml) in methanol (25 ml) at room temperature. After 24 hr., the mixture was evaporated in vacuo and the residue was purified by silica gel column chromatography (eluent, EA) to afford 3.56 g (94%) of (2-methyl-pyridin-4-yl)-methanol as a pale yellow solid. m.p. 58-59 C. 1H NMR (200 MHz, CDCl3) delta 2.45(3H, s), 4.66 (2H, s), 7.06 (1H, d, J=5.2 Hz), 7.14 (1H, s), 8.25 (1H, d, J=5.2 Hz).

References: [1]Patent: US2008/70920,2008,A1 .Location in patent: Page/Page column 97.

11
[ 105250-16-6 ]
2-chloro-6-(2-methyl-pyridin-4-ylmethoxy)-isonicotinonitrile [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 1892 - 1897.

12
[ 105250-16-6 ]
2-chloro-6-(2-methyl-pyridin-4-ylmethoxy)-isonicotinamide [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 1892 - 1897.

13
[ 108-47-4 ]
[ 105250-16-6 ]

Yield	Reaction Conditions	Operation in experiment
		A solution of 4-methylpiridine derivative (20.1) or (20.2) (40 mmol) in dry THF was cooled to -700C under inert atmosphere and to this 1.6 M n-BuLi in hexanes (28 ml_, 44 mmol) was added dropwise. After addition was complete, the solution was stirred for additional 30 min at -700C and DMFA (6.2 mL, 80 mmol) was added. The mixture was stirred for additional 1h 30 min at -70C and quenched with saturated aqueous NH4CI (10 mL) and warmed to room temperature. The mixture was partially evaporated, water (100 mL) was added to the residue and extracted with CHCI3 (3x100 mL). Combined organic phase was washed with brine (100 mL), dried over Na2SO4 filtered and evaporated. The residue was dissolved in MeOH (30 mL) and added dropwise to the suspension of NaIO4 (25.7 g, 120 mmol) in MeOH (30 mL) at the rate to maintain gentle reflux. The mixture was passed trough a short celite column and NaBH4 (4.54g, 120 mmol) was added to the solution. The mixture was stirred for 30 min and a spoonful of SiO2 was added. The solvent was removed in vacuo and the residue applied on a silica gel column. Elution with DCM containing 5% MeOH gave hydroxymethylpiridines (20.1) or (20.2). Intermediate (20.1) or (20.2) (7 mmol) was dissolved in DCM (70 mL) and to the solution thionylchloride (1.05 mL, 14.4 mmol) was added dropwise. The reaction mixture was refluxed for 3 h and evaporated to give (15.16) or (15.17) as a crude product.

References: [1]Synthesis,2002,p. 483 - 486.
[2]Patent: WO2008/142376,2008,A1 .Location in patent: Page/Page column 69-70; 131.

14
dimethyl-[2-(2-methylpyridin-4-yl)vinyl]amine [ No CAS ]
[ 105250-16-6 ]

References: [1]Synthesis,2002,p. 483 - 486.

15
[ 105250-16-6 ]
4-[5-(4-Fluoro-phenyl)-2-(4-methanesulfinyl-phenyl)-3H-imidazol-4-yl]-2-methyl-pyridine [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry,1997,vol. 5,p. 49 - 64.

16
[ 105250-16-6 ]
2-(tert-Butyl-dimethyl-silanyloxy)-1-(4-fluoro-phenyl)-2-(2-methyl-pyridin-4-yl)-ethanone [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry,1997,vol. 5,p. 49 - 64.

17
[ 105250-16-6 ]
[ 152121-89-6 ]

References: [1]Bioorganic and Medicinal Chemistry,1997,vol. 5,p. 49 - 64.

18
[ 105250-16-6 ]
[ 165558-79-2 ]