Name: 73870-24-3|4-(Bromomethyl)pyridine hydrobromide|95%
Brand: Ambeed
SKU: A469649
Price: 6.0 USD
Availability: InStock
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1
[ 65737-59-9 ]
[ 73870-24-3 ]

Reference： [1]Synthesis,1991,p. 1221 - 1227
[2]Chemical Communications,2011,vol. 47,p. 1482 - 1484

2
[ 75-15-0 ]
[ 39604-64-3 ]
[ 73870-24-3 ]
7-methoxy-3-(4-methoxyphenyl)-2-[(pyridin-4-ylmethyl)thio]-4H-1-benzopyran-4-one [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 4032 - 4040

3
[ 75-15-0 ]
[ 39604-80-3 ]
[ 73870-24-3 ]
[ 746640-15-3 ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 4032 - 4040
[2]Bioorganic and Medicinal Chemistry,2005,vol. 13,p. 6571 - 6577

4
[ 952309-42-1 ]
[ 73870-24-3 ]
7-chloro-3-pyrrolidin-1-yl-quinoline-8-carboxylic acid 2-(pyridin-4-ylmethoxy)phenyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With sodium hydroxide; tetrabutylammomium bromide; In toluene; for 10h;Heating / reflux;	To a solution of 2-hydroxyphenyl 7-chloro-3-(pyrrolidin-l-yl)-quinoline-8-carboxylate (3.3 g) in toluene (50 ml) were added tetrabutylammonium bromide (0.8 g), sodium hydroxide (1.7 g) and 4- (bromomethyl)pyridine hydrobromide(2.2 g), and reflux was conducted for 10 hrs. The reaction solution was cooled to room temperature and subjected to extraction with ethyl acetate. The extract was dried over <n="21"/>anhydrous magensium sulfate and concentrated in a vacuum, followed by purification through to afford the object compound (3.2 g, 78%).1H NMR(SOO MHz, CDCl3) delta 8.82 - 6.84(m, 12H), 5.20(s, 2H), 2.88(m, 4H), 1.59(m, 4H);MS m/z 459(M+)

Reference： [1]Patent: WO2007/114672,2007,A1 .Location in patent: Page/Page column 19-20

5
(2S)-3-(4-{2-[(1α,5α,6α)-(3-azabicyclo[3.1.0]hex-6-yl)tert-butoxycarbonylamino]ethoxy}phenyl)-2-ethoxypropionic acid ethyl ester [ No CAS ]
[ 73870-24-3 ]
(2S)-3-(4-{2-[(1α,5α,6α)-tert-butoxycarbonyl-(3-pyridin-4-ylmethyl-3-azabicyclo[3.1.0]hex-6-yl)amino]ethoxy}phenyl)-2-ethoxypropionic acid ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	With potassium carbonate; In acetonitrile; at 0 - 20℃; for 2h;	To a stirred solution of (2S)-3-(4-{2-[(lalpha,5alpha56alpha)-(3-azabicyclo[3.1.0]hex-6-yl)-rert- butoxy-carbonylamino]ethoxy}phenyl)-2-ethoxypropionic acid ethyl ester (Intermediate 13; 0.505 g, 1.09 mmol) in dry acetonitrile (18 ml) was added anhydrous potassium carbonate (0.91 g, 6.56 mmol) and 4-bromomethylpyridine hydrobromide (0.29 g, 1.1 mmol) at 0 0C. The reaction mixture was allowed to come to room temperature and stirred for 2 h. Solvent was removed under reduced pressure and the residue was dissolved in ethyl acetate (35 ml) washed with water (1x5 ml). The organic layer was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to yield the crude product, which was purified by <n="213"/>column chromatography over silica gel (100-200 mesh) using 0.8-M.2 methanol- dichloromethane as an eluent to yield the title compound (0.470 g, 77%). MS: m/z 554 (M+l), 576 (M+23)1HNMR (CDCl3, 400 MHz): delta 1.13 (t, J = 6.8 Hz, 3H), 1.21-1.26 (m, 12H), 1.85-1.90 (m, 3H),' 2.55-2.60 (m, 2H), 2.92 (d, J= 5.6 Hz, 2H), 3.30-3.37 (m, 2H), 3.52-3.65 (m, 4H), 3.70- 3.77 (m, 2H), 3.93 (t, J= 6.4 Hz, IH)5 4.02 (t, J= 4.8 Hz, 2H), 4.13 (q, J= 6.8 Hz, 2H), 6.76 (d, J= 8.4 Hz, 2H), 7.04 (d, J= 8.0 Hz, 2H), 7.35-7.40 (m, 2H), 8.50-8.59 (m, 2H).

Reference： [1]Patent: WO2008/10238,2008,A2 .Location in patent: Page/Page column 211-212

6
[ 73870-24-3 ]
[ 1956-21-4 ]

Reference： [1]Journal of the American Chemical Society,1942,vol. 64,p. 1678,1680
[2]Journal of Organic Chemistry,1958,vol. 23,p. 575,580

7
[ 674290-09-6 ]
[ 73870-24-3 ]
[ 674290-26-7 ]

Yield	Reaction Conditions	Operation in experiment
28%	With tetra-(n-butyl)ammonium iodide; potassium carbonate; In acetone; at 20℃;	Ethyl 4- (4-cyanophenyl)-6-methyl-2-thioxo-1- [3- (trifluoromethyl) phenyl] -1,2, 3,4- tetrahydro-5-pyrimidinecarboxylate (Example 3; 100 mg, 0.22 mmol), [4- (BROMO-] methyl) pyridine hydrobromide (62.5 mg, 0.25 mmol), N, [N, N-TRIBUTYL-L-BUTAN-] aminium iodide (7 mg, 0.03 mmol) and potassium carbonate (65.2 mg, 0.47 mmol) are dissolved in 3 ml acetone and stirred at room temperature overnight. The solvent is removed in vacuo and the product is purified via preparative HPLC (RP18- column; eluent: acetonitrile-water, gradient 10: 90 to 90: 10). Yield: [34 MG] (28% of th.) LC-MS (method 3): Rt = 3.92 min. MS (ESIpos): [M/Z =] 537 [(M+H) +] [IH-NMR] (200 MHz, [DMSO-D6)] : [8] = 8.34 (m, 2H) ; 7.89 (m, 2H); 7.82 (d, 2H); 7.72 (m, 2H); 7.57 (d, 2H); 7.53 (m, 1H); 7.13 (dd, 1H); 5.78 (s, [LH)] ; 3.94-4. 14 (m, 4H); 2.00 (s, 3H); 1.10 (t, 3H) ppm.

Reference： [1]Patent: WO2004/24701,2004,A1 .Location in patent: Page 46

8
[ 470477-56-6 ]
[ 73870-24-3 ]
[ 470477-57-7 ]

Yield	Reaction Conditions	Operation in experiment
75%	With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 20℃;	To a solution of ethyl N-[4-(piperidin-4-yloxy)-3-chlorophenyl]-N-[3-(3-cyanophenyl)-2-(E)-propenyl]sulfamoylacetate (1.10 g) obtained in reference example 71 in N,N-dimethylformamide (30 ml) were added successively <strong>[73870-24-3]4-(bromomethyl)pyridine hydrobromide</strong> (0.59 g) and potassium carbonate (0.59 g) with stirring at room temperature, and the resulting mixture was stirred at room temperature overnight. After stirring, the reaction mixture was diluted with ethyl acetate, and the organic layer was washed with a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue obtained was purified by chromatography on a silica gel column using a mixed solvent of ethyl acetate and methanol (10:1) as the eluent to afford the title compound (0.97 g, yield: 75 %) as a pale yellow amorphous solid. 1H NMR (500MHz, CDCl3) delta ppm : 1.36 (3H, t, J=7.0), 1.86-1.95 (2H, m), 1.95-2.04 (2H, m), 2.38 (2H, m), 2.70 (2H, m), 3.53 (2H, s), 3.98 (2H, s), 4.31 (2H, q, J=7.0), 4.43 (1H, m), 4.46 (2H, d, J=6.5), 6.22 (1H, dt, J=16.0, 6.5), 6.41 (1H, d, J=16.0), 6.92 (1H, d, J=9.0), 7.28 (2H, d, J=6.0), 7.31 (1H, dd, J=9.0, 2.5), 7.40 (1H, t, J=8.0), 7.49-7.54 (2H, m), 7.53 (1H, d, J=2.5), 7.55 (1H, s), 8.54 (2H, d, J=6.0).

Reference： [1]Chemical and Pharmaceutical Bulletin,2009,vol. 57,p. 22 - 33
[2]Patent: EP1375482,2004,A1 .Location in patent: Page 150

9
[ 38521-46-9 ]
[ 73870-24-3 ]
2-(pyridin-4-ylmethylthio)pyridine-3-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%		Reference Example 1 2-(4-Pyridylmethylthio)pyridine-3-carboxylic acid (Reference compound No.1-1) 2-Mercaptonicotinic acid (7.8 g, 50 mmol) and <strong>[73870-24-3]4-(bromomethyl)pyridine hydrobromide</strong> (12.6 g, 50 mmol) were suspended in N,N-dimethylformamide (100 mL) under ice-cooling. Triethylamine (21 ml, 150 mmol) was added dropwise to the suspension, and the whole was stirred at room temperature for 6 hours. Water (300 mL) was added to the reaction mixture, then the aqueous layer was washed with ethyl acetate (100 mL). 2 N hydrochloric acid was added to the aqueous layer to adjust to pH 7, and the precipitated solid was filtered off. The solid was washed with water and diethyl ether, and dried at 50C under reduced pressure to give 7.5 g of the title reference compound as a gray solid. (Yield 61%) 1H-NMR(400MHz,DMSO-d6) delta 4.38(s,2H),7.27(dd,J =8.1,4.8 Hz,1H),7.42(dd,J = 4.4,1.5 Hz,2H),8.22(dd,J = 8.1,1.8 Hz,1H),8.46(dd,J = 4.4,1.5 Hz,2H),8.63(dd,J = 4.8,1.8 Hz,1H),13.70(br s,1H)

Reference： [1]Patent: EP1602647,2005,A1 .Location in patent: Page/Page column 40
[2]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 7234 - 7238

10
[ 73870-24-3 ]
[ 477932-80-2 ]

Yield	Reaction Conditions	Operation in experiment
66%		6-fluoroisatoic anhydride (79, 0.3 g, 1.65 mmol) was dissolved in anhydrous DMA (8 mL). The solution was stirred under an N2 atmosphere and NaH (0.073 g, 1.82 mmol, 60% dispersion in mineral oil) was added. The mixture was stirred for 10 min and additional sodium hydride (0.066 g, 1.65 mmol) was added followed by a solution of <strong>[73870-24-3]4-(bromomethyl)pyridine hydrobromide</strong> (0.46 g, 1.82 mmol) and DMA (10 mL). The reaction was heated to 70 C. for 3 h, cooled to room temperature and finally in an ice bath. The reaction mixture was poured into a cold saturated NH4Cl solution (150 mL) and thrice extracted with EtOAc (75 mL). The combined organic layers were washed with water (40 mL), brine. The solution was dried (Na2SO4), filtered and evaporated to afford a solid which was dried in a vacuum then triturated with Et2O/hexane (1:2) to afford 300 mg (66%) of 81: ms [M+H]+=273.

Reference： [1]Patent: US2006/40927,2006,A1 .Location in patent: Page/Page column 40

11
[ 73870-24-3 ]
[ 1044718-04-8 ]

Yield	Reaction Conditions	Operation in experiment
		4-Nitro-1-pyridin-4-ylmethy1-lH-indole: To a cooled solution of 1.0 g (6.2 mmol, leq.) of 4-nitroindole in 25 mL of THF is added 0.44 g (19 mmol, 3 eq.) of NaH (95% dry). The resulting reaction mixture is stirred at 0 C for 30 min and treated with 2.3 g (9.3 mmol, 1.5 eq.) of 4-bromomethylpyridine hydrobromide and the reaction mixture is stirred for 16 hrs while warming up to rt. Water is added and the aqueous layer was extracted with EtOAc (3 x 75 mL), the organic layers combined and dried over anhydrous MgSO4. The resulting solid is then purified by column chromatography (5% MeOH : 95% EtOAc) affording 4-nitro-1-pyridin-4-ylmethyl-lH-indole as a yellow solid.

Reference： [1]Patent: WO2006/76593,2006,A1 .Location in patent: Page/Page column 44

12
[ 73870-24-3 ]
[ 1044717-94-3 ]

Yield	Reaction Conditions	Operation in experiment
		4-Nitro-1-pyridin-4-ylmethyl-lH-indazoIe: To a cooled solution of 4- EPO <DP n="47"/>nitroindazole (1.0 g, 6.10 mmol) in THF (25 mL) is added NaH (0.44 g, 95%, 18.0 mmol). The resulting reaction mixture is stirred at 0 C for 30 min then treated with 4- bromomethylpyridine hydrobromide (2.3 g, 9.2 mmol, 1.5 eq.) and the reaction mixture is stirred for 16 hrs while warming up to rt. Water (25 mL) is added and the aqueous layer is extracted with EtOAc (3 x 75 mL), and the organic layers are combined and dried over anhydrous MgSO4. The resulting crude is then purified by column chromatography (5% MeOH : 95% EtOAc) to afford 4-nitro-1-pyridin-4-ylmethy1-lH-indazole as a yellow solid.

Reference： [1]Patent: WO2006/76593,2006,A1 .Location in patent: Page/Page column 45-46

13
[ 73870-24-3 ]
C₃₆H₃₄N₄O₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Example 89 3-Cyclohexyl-2-[2-(2,4-dimethyl-thiazol-5-y1)-quinolin-6-y1]-l-pyridin-4-y1methyl- 1H-indole-6-carboxylic acid (289)[0321] To a solution of the indole compound 137 (94 mg, 0.19 mmol) in DMF (2 mL) was added NaH ( 27 mg, 5 eq). After 5 minutes stirring at room temperature 4- bromomethyl pyridine hydrobromide was added and the mixture stirred for 4 hours. The reaction was then quenched with water (1 mL) which precipitated the product. It was then spun down to a pellet and redissolved in 5 mL of methanol : water (5% LiOH) and heated to 50 C for 8 hrs. The product was then purified by RP-HPLC.Yield 35.2 mg, 30%. MS: 573.2 (M+H+); H1-NMR (DMSO-d6): delta(rhorhom) 8.61 (d, 2H, J=5.1), 8.44 (d, 1H, J=8.1), 8.01-7.62 (m,7H), 7.2 (d, 1H, J= 5.1), 5.6 (s, 2H), 2.69 (s, 3H), 2.65 (s, 3H), 2.62 (m, 1H) 1.95-1.10 (m, 10H).

Reference： [1]Patent: WO2006/76529,2006,A1 .Location in patent: Page/Page column 138

14
[ 73870-24-3 ]
5,6-dichloro-1-pyridin-4-ylmethyl-2-(2,2,2-trifluoro-ethyl)-1H-benzoimidazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		NaH (60%) (120 mg, 3 mmol) was added into a solution of dichloro-2-(2,2,2-trifluoro-ethyl)-1H-benzoimidazole (269 mg, 1 mmol) in DMF (5 ml) at 0C. The resulting mixture was stirred at 0C for half hour. <strong>[73870-24-3]4-(bromomethyl)-pyridine hydrobromide</strong> (379.5 mg, 1.5 mmol) was then added to the reaction mixture at 0C. The reaction temperature was raised to 25C and then the reaction mixture was stirred for 18 hours. NH4Cl (aq.) was added and extracted with EtOAc. The organic layer was washed with brine, then dried over anhydrous MgSO4. The solvent was distilled out under reduced pressure. Column chromatography (silica gel, EtOAc / hexanes (30% to 100%) yielded the title compound as a white solid. MS m/z (M+H) 360.

Reference： [1]Patent: WO2006/39243,2006,A1 .Location in patent: Page/Page column 88-89

15
[ 913537-98-1 ]
[ 73870-24-3 ]
C₂₈H₂₀N₂O₄S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
22%	With triethylamine; In dichloromethane; at 20℃; for 6h;	The thiol (32mg, 0.127mmol), 4-bromomethylpyridine hydrobromide (40mg, 0.106mmol) and triethylamine (32ul, 0.2296 mmol) were added to anhydrous dichloromethane (1.5ml) and stirred for 6h at room temperature. The mixture was quenched with water, the organics extracted with dichloromethane (3 x 10ml) and evaporated to a residue. Preparative thin layer chromatography (SiO2, 1% MeOH in dichloromethane) yielded the 4-pyridinyl phenoxazine (13mg, 22%) as a yellow solid.

Reference： [1]Patent: WO2006/113509,2006,A2 .Location in patent: Page/Page column 86

16
[ 348-36-7 ]
[ 73870-24-3 ]
[ 921039-96-5 ]

Yield	Reaction Conditions	Operation in experiment
		1.1. Ethyl 5-fluoro-1-[(pyrid-4-yl)methyl]-1H-indole-2-carboxylate A solution of 1 g (4.73 mmol) of <strong>[348-36-7]ethyl 5-fluoro-1H-indole-2-carboxylate</strong> is added dropwise to a suspension of 0.38 g (9.45 mmol) of 60percent sodium hydride in 10 ml of dimethylformamide, stirred at 0° C. under argon. The mixture is stirred for 30 minutes at 0° C. and then for 30 min at 20° C. The reaction mixture is cooled and 1.24 g (4.2 mmol) of 4-bromomethylpyridine hydrobromide are added portionwise. The mixture is stirred for 30 minutes at 0° C. and then for 30 minutes at 20° C. The reaction mixture is cooled again to 0° C. and a further 0.38 g (9.45 mmol) of 60percent sodium hydride in 10 ml of dimethylformamide is added. After 30 minutes at 0° C., 1.24 g (4.2 mmol) of 4-bromomethylpyridine hydrobromide are added portionwise. The reaction mixture is then stirred for 20 hours at 20° C. After this time, the mixture is poured into a solution of 100 ml of ice-water and 100 ml of ethyl ether. The organic phase is separated out and the aqueous phase is re-extracted with 100 ml of ethyl ether. The organic phases are combined, washed with 50 ml of water and then dried over sodium sulfate, filtered and then concentrated under reduced pressure. The residue is purified by preparative chromatography (eluent: dichloromethane/acetone). 0.65 g of expected product is obtained in the form of an oil, which is used without further purification in the subsequent synthesis.

Reference： [1]Patent: US2008/146646,2008,A1 .Location in patent: Page/Page column 7; 8

17
[ 1058161-07-1 ]
[ 73870-24-3 ]
[ 1058161-36-6 ]

Yield	Reaction Conditions	Operation in experiment
18%	With sodium hydride; In N,N-dimethyl-formamide; at 90℃;	Example 21.1: 2-(4-{2-[4-(Pyridin-4-ylmethoxy)-phenyl]-acetyI}-piperazin-1-yl)-nicotinonitrile. A mixture of 2-{4-[2-(4-hydroxy-phenyl)-acetyl]-piperazin-l-yl}-nicotinonitrilc (Example 1.4) (500 mg, 1.55 mmol), sodium hydride (75 mg, 3,12 mmol), 4-bromomethyl- pyridine hydrobromide (393 mg, 1,55 mmol) and N,N-dimethylformamide (20 mL) was stirred at 90 C. The reaction mixture was cooled to room temperature, quenched with water and diluted with ethyl acetate. The organic layer was separated, washed with water, washed with brine, dried over sodium sulfate, filtered and concentrated. The residue was purified on silica gel to give 2-(4- {2- [4-(pyridin-4-ylmethoxy)-phenyl] -acetyl } -piperazin-1-yl)- nicotinonilrile (1 15 mg, 18 %). 1H NMR (300 MHz, CDCl3): delta(ppm) 8.35 (bs, 2H), 8.08 (dd, <n="43"/>IH), 7.52 (dd, IH), 7.10 (m, 2H), 6.95 (d, 2H), 6.67 (d, 2H), 6.55 (m, IH), 4.82 (s, 2H), 3.53 (m, 2H), 3.48 (s, 2H), 3.38 (m, 4H), 3.27 (m, 2H).

Reference： [1]Patent: WO2008/112440,2008,A1 .Location in patent: Page/Page column 41-42

18
4-(2-(4-(trifluoromethyl)benzyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8-carboxamido)piperidine dihydrochloride [ No CAS ]
[ 73870-24-3 ]
[ 1160786-60-6 ]

Yield	Reaction Conditions	Operation in experiment
60%	With triethylamine; In N,N-dimethyl-formamide; at 20℃;	Step 2; A solution of the dihydrochloride salt of step 1, above (65 mg, 0.12 mmol) was dissolved in DMF (2.0 mL) and <strong>[73870-24-3]4-(bromomethyl)pyridine hydrobromide</strong> (2×35 mg, 2×0.14 mmol) and triethylamine (2×80 muL, 2×58 mg, 2×570 mumol) were added. The resulting reaction mixture was allowed to stir at room temperature overnight, poured into saturated sodium bicarbonate solution (20 mL) to give an off-white solid which was triturated with ethyl ether to provide N-(1-(pyridin-4-ylmethyl)piperidin-4-yl)-2-(4-(trifluoromethyl)benzyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8-carboxamide (Compound 50, 60%). 1H NMR (DMSO-d6, 300 MHZ) 11.02 (s, 1H), 8.49 (d, J=4.7 Hz, 2H), 7.99 (d, J=8.0 Hz, 1H), 7.84 (s, 1H), 7.71 (d, J=8.0 Hz, 2H), 7.62 (d, J=8.3 Hz, 2H), 7.55 (d, J=8.3 Hz, 1H), 7.31 (d, J=4.7 Hz, 2H), 7.25 (d, J=8.3 Hz, 1H), 3.86 (s, 2H), 3.82-3.70 (m, 1H), 3.63 (s, 2H), 3.50 (s, 2H), 2.90-2.74 (m, 6H), 2.06 (t, J=11.1 Hz, 2H), 1.77 (d, J=10.2 Hz, 2H), 1.60 (q, J=10.9 Hz, 2H) ppm; MS (ES) 548 (M+H).

Reference： [1]Patent: US2009/163511,2009,A1 .Location in patent: Page/Page column 60

19
[ 1148015-61-5 ]
[ 73870-24-3 ]
[ 1148015-62-6 ]

Reference： [1]Chemical Communications,2009,p. 1404 - 1406

20
[ 1166181-79-8 ]
[ 73870-24-3 ]
[ 1166185-25-6 ]

Yield	Reaction Conditions	Operation in experiment
49%	With caesium carbonate; In N,N-dimethyl-formamide; at 60℃; for 3h;	a) Methyl 2-{2-[4-(pyridin-4-ylnnethoxy)phenyl]ethyl}-5-phenylpentanoate 4-(Bromonnethyl)py?dine hydrobromide (500 mg, 1.976 mmol) was added to a suspension of methyl 2-[2-(4-hydroxyphenyl)ethyl]-5-phenylpentanoate (400 mg, 1.28 mmol) and Cs2CO3 (1.30 g, 3.98 mmol) in DMF (20 ml_). The reaction mixture was warmed up to 60 0C and stirred for 3 h. It was allowed to reach r.t. and poured into H2O (150 ml_), taken up to pH = 3 with HCI and extracted with Et2O (100 ml_). The organic layer was dried over Na2SO4 (anhydrous), filtered and concentrated. The crude residue was purified by flash chromatography on SiO2 (10?80% EtOAc/hexanes), to give 245 mg of methyl 2-{2-[4-(pyridin-4-ylmethoxy)phenyl]ethyl}-5-phenylpentanoate(colourless oil, yield: 49%).1H NMR (CDCI3, 250 MHz) delta ppm: 8.60 (m, 2H), 7.34 (m, 2H), 7.26 (m, 2H), 7.21 -7.03 (m, 5H), 6.85 (m, 2H), 5.07 (s, 2H), 3.67 (s, 3H), 2.61 -2.33 (m, 5H), 1.90 (m, 1 H), 1.75-1.46 (m, 5H).

Reference： [1]Patent: WO2009/80722,2009,A2 .Location in patent: Page/Page column 86

21
[ 73870-24-3 ]
[ 105-53-3 ]
[ 101829-74-7 ]

Yield	Reaction Conditions	Operation in experiment
79%		To 50 mL of DMF (50 mL) at RT was gradually added with stirring NaOMe (4.13 g, 76 mmol) and the resulting reaction mixture was cooled to 5-10. Diethyl malonate (11.6 mL, 76 mmol) was added to the reaction mixture and stirred at RT for 1h. 4-(Bromomethyl)pyridine hydrobromide 5 (12 g, 47 mmol) dissolved in DMF (22 mL) was added to the reaction mixture over a period of 10 min at 5 -10 . The resulting reaction mixture was stirred for 6h at RT. After completion of the reaction by TLC, the reaction mixture was quenched with ice cold water (500 ml) and extracted with DCM (2 x 250 mL). The combined organic layers were dried over Na2SO4. Filtered the organic layer and concentrated under reduced pressure to give crude product as pale red color oil. The obtained crude compound was purified by column chromatography (SiO2, 60-120 mesh, 40% EtOAc/hexane) to get diethyl 2-(pyridin-4-ylmethyl)malonate 6 (9.4 g, 79%) as pale red color oil. 1H NMR (400 MHz, CDCl3): 1.19 (t, 6H, J = 7.2 Hz), 3.22 (d, 2H, J = 7.6 Hz), 3.63 (t, 1H, J = 7.6 Hz), 4.14 (m, 4H) 7.23 (d, 2H, J = 6.4 Hz) 8.51 (d, 2H, J = 3.2 Hz); 13C NMR (100 MHz, CDCl3): 13.91, 14.05, 33.80, 52.46, 52.65, 61.78, 124.01, 124.18, 146.93, 149.86, 149.94, 168.32; Mass: m/z = 252.1 [M+H]+.

Reference： [1]Indian Journal of Heterocyclic Chemistry,2015,vol. 24,p. 459 - 464

22
2,2,2-trifluoro-N-{4-[(2,2,2-trifluoroacetylamino)methyl]piperidin-4-yl}acetamide hydrochloride [ No CAS ]
[ 73870-24-3 ]
[ 1160755-65-6 ]

Yield	Reaction Conditions	Operation in experiment
	In N,N-dimethyl-formamide; mineral oil;	Step 3 To a suspension of NaH (170 mg of a 60% dispersion in mineral oil, 4.25 mmol) in anhydrous DMF (20 ml) is added 2,2,2-trifluoro-N-{4-[(2,2,2-trifluoro-acetylamino)-methyl]-piperidin-4-yl}-acetamide hydrochloride) (500 mg, 1.4 mmol) followed by 4-bromomethylpyridine hydrobromide (350 mg, 1.4 mmol). The reaction mixture is stirred at room temperature for 3 hours. The reaction mixture is quenched with sat. NH4Cl solution and is concentrated in vacuo. The residue is purified by column chromatography (basic alumina, MeOH/DCM) to obtain 2,2,2-Trifluoro-N-[1-pyridin-4-ylmethyl-4-(2,2,2-trifluoro-acetylamino)-piperidin-4-ylmethyl]-acetamide as off-white solid; [M+H]+ 413.
	With sodium hydride; In N,N-dimethyl-formamide; mineral oil; at 20℃; for 3h;	To a suspension of NaH (170 mg of a 60% dispersion in mineral oil, 4.25 mmol) in anhydrous DMF (20 ml) is added 2,2,2-trifluoro-N-{4-[(2,2,2-trifluoro-acetylamino)-methyl]-piperidin-4-yl}-acetamide hydrochloride) (500 mg, 1.4 mmol) followed by 4-bromomethylpyridine hydrobromide (350 mg, 1.4 mmol). The reaction mixture is stirred at room temperature for 3 hours. The reaction mixture is quenched with sat. NH4Cl solution and is concentrated in vacuo. The residue is purified by column chromatography (basic alumina, MeOH/DCM) to obtain 2,2,2-Trifluoro-N-[1-pyridin4-ylmethyl-4-(2,2,2-trifluoro-acetylamino)-piperidin-4-ylmethyl]-acetamide as off-white solid; [M+H]+ 413.

Reference： [1]Patent: US2011/98311,2011,A1
[2]Patent: US2015/231142,2015,A1 .Location in patent: Paragraph 2637

23
[ 5597-50-2 ]
[ 73870-24-3 ]
[ 1160755-24-7 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;	Step 1 3-[4-(Pyridin-4-ylmethoxy)-phenyl]-propionic acid To a solution of Methyl 3-(4-hydroxyphenyl)propanoate (0.5 g, 2.77 mmol) in dry DMF (10 ml) is added potassium carbonate (0.76 g, 5.55 mmol) followed by <strong>[73870-24-3]4-(bromomethyl)pyridine hydrobromide</strong> (0.7 g, 2.77 mmol). The reaction mixture is stirred at room temperature overnight then poured into water (80 ml) and extracted with EtOAc (40 ml). The organic phase is washed with brine, dried (MgSO4) and the solvent removed in vacuo to yield a dark brown oil. Chromatography (SiO2, EtOAc) yields 3-[4-(Pyridin-4-ylmethoxy)-phenyl]-propionic acid methyl ester as a colourless oil; [M+H]+ 272.0
	With potassium carbonate; In N,N-dimethyl-formamide;	Step 1 3-[4-(Pyridin-4-ylmethoxy)-phenyl]-propionic acid To a solution of Methyl 3-(4-hydroxyphenyl)propanoate (0.5 g, 2.77 mmol) in dry DMF (10 ml) is added potassium carbonate (0.76 g, 5.55 mmol) followed by <strong>[73870-24-3]4-(bromomethyl)pyridine hydrobromide</strong> (0.7 g, 2.77 mmol). The reaction mixture is stirred at room temperature overnight then poured into water (80 ml) and extracted with EtOAc (40 ml). The organic phase is washed with brine, dried (MgSO4) and the solvent removed in vacuo to yield a dark brown oil. Chromatography (SiO2, EtOAc) yields 3-[4-(Pyridin-4-ylmethoxy)-phenyl]-propionic acid methyl ester as a colorless oil; [M+H]+ 272.0.
	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;	To a solution of Methyl 3-(4-hydroxyphenyl)propanoate (0.5 g, 2.77 mmol) in dry DMF (10 ml) is added potassium carbonate (0.76 g, 5.55 mmol) followed by <strong>[73870-24-3]4-(bromomethyl)pyridine hydrobromide</strong> (0.7 g, 2.77 mmol). The reaction mixture is stirred at room temperature overnight then poured into water (80 ml) and extracted with EtOAc (40 ml). The organic phase is washed with brine, dried (MgSO4) and the solvent removed in vacuo to yield a dark brown oil. Chromatography (SiO2, EtOAc) yields 3-[4-(Pyridin-4-ylmethoxy)-phenyl]-propionic acid methyl ester as a colorless oil; [M+H]+ 272.0.

Reference： [1]Patent: US2010/130506,2010,A1 .Location in patent: Page/Page column 113-114
[2]Patent: US2011/98311,2011,A1
[3]Patent: US2015/231142,2015,A1 .Location in patent: Paragraph 2544

24
[ 852330-31-5 ]
[ 73870-24-3 ]
[ 1244028-08-7 ]

Yield	Reaction Conditions	Operation in experiment
48%		A mixture of methyl 5-bromo-3-[ (trifluoroacetyl) amino] thiophene-2-carboxylate (500 mg, 1.51 mmol) , 4- (bromomethyl) pyridine hydrobromide (457 mg, 1.81 mmol), cesium carbonate (1.72 g, 5.29 mmol) and DMA (15 mL) was stirred at 800C for 2 h. Then, water was added to quench the reaction. The organic materials were extracted with EtOAc. The combined extracts were washed with water and brine, dried over Na2SO4 and filtered. After removal of the solvent at reduced pressure, the residue was dissolved in MeOH (5 mL) . To the solution were added potassium carbonate (500 mg) and water (2.5 mL) . The mixture was stirred at room temperature for 2 h. After removal of the solvent at reduced pressure, the organic materials were extracted with EtOAc. The combined extracts were washed with brine, dried over Na2SO4 and filtered. After removal of the solvent at reduced pressure, the residue was purified by column chromatography (Purif, silica gel, hexane to 50:50 hexane/EtOAc) to give the title compound (238 mg, 48%) as a yellow solid: 1H NMR (300 MHz, CDCl3) delta 3.82 (3H, s) , 4.47 (2H, d, J = 6.2 Hz), 6.46 (IH, s), 7.23 (2H, d, J = 5.9 Hz), 7.34 (IH, br s) , 8.53-8.63 (2H, m) .

Reference： [1]Patent: WO2010/101302,2010,A1 .Location in patent: Page/Page column 247

25
[ 73870-24-3 ]
[ 56-04-2 ]
[ 904552-11-0 ]

Yield	Reaction Conditions	Operation in experiment
26%	With triethylamine; In ethanol; at 20℃;	6-methyl-2-sulfanylpyrimidin-4-ol (300 mg, 2.1 mmol) was dissolved in absolute ethanol (10 mL), then triethylamine (650 muL, 4.6 mmol) and 4-(bromomethyl)pyridin- 1-ium bromide (587 mg, 2.3 mmol) were added. The mixture was stirred overnight at room temperature, and the solvent was evaporated. The residue was dissolved in DCM and purified on silica gel using 10% DCM/MeOH to afford, after washing with water, 6-methyl-2-[(pyridin-4-ylmethyl)sulfanyl]pyrimidin-4-ol as white solid (128 mg, 26% yield); 1H NMR (400 MHz, MeOJ4): 62.24 (s, 3H), 4.47 (s, 2H), 6.00 (s, IH), 7.52 (dd, / = 4.5 Hz, J = 1.6 Hz, 2H), 8.45 (dd, J = 4.5 Hz, J = 1.6 Hz, 2H).

Reference： [1]Patent: WO2010/132999,2010,A1 .Location in patent: Page/Page column 82-83

26
[ 84625-56-9 ]
[ 73870-24-3 ]
[ 1263295-62-0 ]

Yield	Reaction Conditions	Operation in experiment
62%	With caesium carbonate; In water; N,N-dimethyl-formamide; at 20℃; for 24h;	General procedure: The 7-alkoxy-1-methyl-beta-carbolines (3a-o) were synthesized according to a previously reported procedure.13 The appropriate alkyl halide (by portion) or 1-tosyl-4,4,4-trifluorobutane (for compound 3e) and cesium carbonate were added to harmol (2) dissolved in anhydrous dimethylformamide (DMF). Then, the reaction mixture was stirred at room temperature or heated for several hours. At the end of the reaction, the mixture was cooled and diluted with dichloromethane, washed once with water and three times with brine. The organic layer was dried over MgSO4 and concentrated. The crude product was purified by liquid chromatography.

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 134 - 144

27
[ 73870-24-3 ]
[ 56059-30-4 ]
[ 1273318-25-4 ]

Reference： [1]Chemical Communications,2011,vol. 47,p. 1482 - 1484

28
[ 73870-24-3 ]
[ 141699-55-0 ]
[ 1309207-57-5 ]

Yield	Reaction Conditions	Operation in experiment
41%		Step 3: tert- Butyl 3-(pyridin-4-ylmethoxy)azetidine-l-carboxylateA solution of A/-Boc-azetidin-3-ol (500 mg, 2.89 mmol) in THF (10 ml_) was cooled to 0 C. t-BuOK (1M in THF, 11.6 ml_) was added dropwise and the reaction mixture was stirred at room temperature for 0.25 h then cooled to 0 C. A solution of 4- bromomethylpyridine hydrobromide (2.19 g, 8.67 mmol) in dichloromethane (5 ml_) stirred with DIPEA (4 ml_, 24 mmol) for 0.5h was then added. The reaction mixture was stirred at room temperature for 24 h. The reaction mixture was diluted with H20 and extracted twice with EtOAc. The organics were separated from the aqueous layer and combined, dried over Na2S04 and concentrated to dryness. The crude mixture was purified by column chromatography (eluent: Pentane/EtOAc, 1/1 to 7/3) to give the title product (313 mg, 41%) as a yellow oil.LCMS (ESI+) m/z 265 (M)+ : 28%.*H NMR (DMSO-c/e, 300 MHz) : delta (ppm) : 8.54 (d, J = 5.9 Hz, 2H), 7.34 (d, J = 5.9 Hz, 2H), 4.49 (s, 2H), 4.39-4.25 (m, 1H), 4.06-3.90 (m, 2H), 3.80-3.65 (m, 2H), 1.37 (s, 9H).

Reference： [1]Patent: WO2011/61214,2011,A1 .Location in patent: Page/Page column 77

29
[ 1313440-29-7 ]
[ 73870-24-3 ]
[ 1313440-46-8 ]

Yield	Reaction Conditions	Operation in experiment
50%	With sodium hydride; In N,N-dimethyl-formamide; at 20℃; for 1h;Inert atmosphere;	To a solution of tert-butyl (1-(4-(2-oxo-7-phenyl-2,3-dihydro-1 H-pyrido[2,3-b][1 ,4]oxazin- 6-yl)phenyl)cyclobutyl)carbamate (35 mg, 0.07 mmol) in dry DMF (1 ml) was added sodium hydride (7 mg, 0.18 mmol) and 4-(bromomethyl)pyridine.HBr (23 mg, 0.09 mmol) under nitrogen. The resulting mixture was stirred for 1 hour at room temperature. A saturated solution of NaHC03 was added and the mixture was extracted with dichloromethane (3 x 10ml) using a phase separator (Isolute SPE). The combined organic phases were concentrated to dryness under reduced pressure. The resulting residue was purified by Biotage silica gel chromatography (gradient 0 to 80% EtOAc in cyclohexane) to give the title compound (21 mg, 50%). 1H NMR (500 MHz,CDCI3): 8.54 (2H,s), 7.19 -7.12 (9H,m), 6.97 (1 H,s), 6.93-6.91 (2H,m), 5.1 1 (2H, s), 4.98 (1 H, br s), 4.95 (2H, s), 2.52-2.20 (4H, m), 2.00-1.95 (1 H, m), 1.75 -1.70 (1 H, m), 1.44-1.15 (9H, br).

Reference： [1]Patent: WO2011/77098,2011,A1 .Location in patent: Page/Page column 80

30
[ 1346226-87-6 ]
[ 73870-24-3 ]
[ 1346227-11-9 ]

Yield	Reaction Conditions	Operation in experiment
54%	With potassium carbonate; In acetonitrile; for 3h;Reflux;	To a round-bottom flask was charged with compound 12a (210 mg, 0.33 mmol), <strong>[73870-24-3]4-(bromomethyl)-pyridine hydrobromide</strong> salt (85 mg, 0.34 mmol), K2C03 (110 mg) and ACN (15 mL). The reaction mixture was stirred at refluxing temperature for 3 hr. When TLC indicated complete consumption of starting material, the reaction mixture was poured into a separating funnel containing water. The mixture was continuously extracted with CH2CI2. The combined organic layers were dried over MgS04, filtered and evaporated to give a crude reaction mixture, which was subjected to purification by flash column chromatography on silica gel with 10-20 % acetone in CH2CI2 as eluent to furnish the titled compound 21 as pale brown oil (130 mg, 54%): 1H NMR (CDCI3) delta 2.81 (t, J = 5.6 Hz, 4H), 3.63 (t, J = 6.0 Hz, 4H), 3.78 (t, J = 4.8 Hz, 4H), 3.84 (s, 2H), 4.14 (t, J = 4.8 Hz, 4H), 6.70 (s, 2H), 6.99 (d, J = 8.8 Hz, 4H), 7.30 (d, J = 5.2 Hz, 2H), 7.37 (dd, J = 8.0, 8.4 Hz, 2H), 7.51 (d, J = 8.4 Hz, 2H), 7.62 (dd, J = 8.0, 8.4 Hz, 2H), 7.83 (d, J = 8.8 Hz, 4H), 8.17 (d, J = 8.0 Hz, 2H), 8.49 (d, J = 5.2 Hz, 2H); 3C NMR (CDCI3) delta 54.2, 58.7, 67.6, 69.3, 70.0, 106.2, 115.0, 117.9, 123.7, 123.9, 124.2, 125.1 , 125.6, 127.9, 133.6, 149.6, 156.1 , 161.5, 163.2, 178.3; LRMS (ESI) m/z 725 (M+ + H, 25); HRMS (ESI) Calcd for C44H41N2Oa(M+ + H) 725.2863, found 725.2859

Reference： [1]Patent: WO2011/137516,2011,A1 .Location in patent: Page/Page column 37
[2]Journal of Medicinal Chemistry,2012,vol. 55,p. 1999 - 2014

31
[ 147284-02-4 ]
[ 73870-24-3 ]
[ 1357620-85-9 ]

Yield	Reaction Conditions	Operation in experiment
50%		General procedure: NaH (60% in oil, 3 mol equiv.) was added in one portion to the alcohol 7 dissolved in dry THF (?5 mL/mmol) and the reaction mixture was stirred for 10 min under an Ar atmosphere. The substituted benzyl bromide (1-1.2 mol equiv.) was then added and the reaction mixture was stirred at rt for a period of 48-72 h. H2O (10-20 mL) was then added and the THF removed under reduced pressure. The remaining aqueous liquid was extracted with EtOAc or CH2Cl2 (3 × 20 mL), which was combined, washed with brine, dried over MgSO4 and removed in vacuo. The alkylated product was then obtained after column chromatography with flash silica.

Reference： [1]European Journal of Medicinal Chemistry,2012,vol. 48,p. 1 - 15

32
[ 1380646-35-4 ]
[ 73870-24-3 ]
[ 1380646-65-0 ]

Yield	Reaction Conditions	Operation in experiment
37%		Example 55 N-Benzooxazol-2-yl-2-(4-methanesulfonyl-phenyl)-3-pyridin-4-yl-propionamide To a slurry of sodium hydride (29 mg of 60% in oil dispersion, 0.73 mmol) in DMF (1 mL) under nitrogen at 0 C. was added a solution of N-benzooxazol-2-yl-2-(4-methanesulfonylphenyl)acetamide (prepared as in example 5, 100 mg, 0.3 mmol) in DMF (2 mL). The reaction mixture was stirred at room temperature for 2 h. A suspension of 4-bromomethylpyridine hydrobromide (77 mg, 0.3 mmol) was suspended in DMF (1.5 mL) and to that was added sodium hydride (12 mg of 60% in oil dispersion, 0.3 mmol). The resulting 4-bromomethylpyridine solution was added to the above solution. The combined reaction mixture was stirred at room temperature for 2 h. The reaction mixture was quenched with saturated aqueous NH4Cl, diluted with H2O and extracted 1 time with ether and 2 times with CH2Cl2. The combined organic extracts were washed with saturated aqueous NaCl, dried over Na2SO4 and concentrated in vacuo. Purification by chromatography (silica, 1-3% methanol in CH2Cl2 gradient) afforded N-benzooxazol-2-yl-2-(4-methanesulfonyl-phenyl)-3-pyridin-4-yl-propionamide: 1H NMR (300 MHz, CHLOROFORM-d) delta ppm 2.94-3.19 (s, m, 5H) 3.61 (dd, J=13.94, 8.67 Hz, 1H) 7.13 (d, J=5.65 Hz, 2H) 7.19-7.33 (m, 3H) 7.34-7.51 (m, 2H) 7.57 (d, J=8.29 Hz, 2H) 7.84 (d, J=8.29 Hz, 2H) 8.40 (d, J=4.90 Hz, 2H).

Reference： [1]Patent: US2012/149718,2012,A1 .Location in patent: Page/Page column 47

33
[ 885521-22-2 ]
[ 73870-24-3 ]
[ 1383475-17-9 ]

Yield	Reaction Conditions	Operation in experiment
71%	With N,N,N?,N?-tetramethyl-N?-tert-butylguanidine; In acetonitrile;	Step A: Preparation of 3 -iodo-4-nitro- 1 -(pyridin-3 -ylmethyl)- 1 H-indazole : To a flask was added 3 -iodo-4-nitro-l H-indazole (0.300 g, 1.04 mmol) and 4- (bromomethyl)pyridine hydrobromide (0.315 g, 1.25 mmol) which were slurried in CH3CN (5.0 mL). 2-tert-Butyl-l,l,3,3-tetramethylguanidine (0.460 mL, 2.28 mmol) was added and the mixture was stirred overnight. The mixture was diluted with water (20 mL) and stirred for 15 minutes and filtered. The collected solids were washed with water followed by Et20 and hexanes, and dried under vacuum to provide the title compound as a brown powder (0.304 g, 71%), which was used directly in the subsequent step.

Reference： [1]Patent: WO2012/82689,2012,A1 .Location in patent: Page/Page column 151

34
[ 1076-74-0 ]
[ 73870-24-3 ]
[ 1383924-50-2 ]

Yield	Reaction Conditions	Operation in experiment
41%	With sodium hydride; In N,N-dimethyl-formamide; mineral oil; at 80℃; for 48h;	The following compounds or the precursors to them were prepared according to general route 3: 2-(5-methoxy-2-methyl-l-^yridin-4-ylmethyl)-lH-indol-3-yl)-N-(2-methoxypyridin- 4-yl)-2-oxoacetamide (16); [00292] To a solution of 5-methoxy-2-methyl- 1 H-indole (500 mg, 3.10 mmol) in N,N- dimethylformamide (200 mL) was carefully added a 60% dispersion in mineral oil of sodium hydride (248 mg, 6.20 mmol), followed by <strong>[73870-24-3]4-(bromomethyl)pyridine hydrobromide</strong> (785 mg, 3.10 mmol). The reaction mixture was stirred at 80 C for 48 hours after which it was quenched by the addition of saturated sodium bicarbonate solution (50 mL) extracted with dichloromethane (3 x 20 mL), dried (magnesium sulfate), filtered, and concentrated to a residue. Purification was achieved by silica gel chromatography using 5 to 20% of a 7:1 acetonitrile:methanol solution in dichloromethane over 60 minutes to afford 5-methoxy-2- methyl-l-(pyridin-4-ylmethyl)-l H-indole (0.324 g, 1.28 mmol, 41% yield) as a yellow solid. 1H NMR (400 MHz, CDC13) delta (ppm): 8.49 (dd, 2H), 7.05 (d, IH), 6.99 (d, IH), 6.83 (m, 2H), 6.76 (dd, IH), 6.29 (s, IH), 5.26 (s, 2H), 3.84 (s, 3H). LCMS: [ES]+ found 253.13.[00293] 2-(5-methoxy-2-methyl- 1 -(pyridin-4-ylmethyl)- 1 H-indol-3-yl)-N-(2- methoxypyridin-4-yl)-2-oxoacetamide was synthesized as a yellow solid in 7% yield starting from 5-methoxy-2-methyl-l-(pyridin-4-ylmethyl)-l H-indole using general procedure G. NMR MHz, CDC13) delta (ppm): 9.03 (br. s, IH), 8.55 (dd, 2H), 8.14 (d, IH), 7.80 (d, IH), 7.26 (d, IH), 7.15 (dd, IH), 7.07 (d, IH), 6.92 (d, 2H), 6.88 (dd, IH), 5.37 (s, 2H), 3.96 (s, 3H), 3.89 (s, 3H), 2.68 (s, 3H); LCMS: [ES]+ found 431.20.

Reference： [1]Patent: WO2012/88469,2012,A1 .Location in patent: Page/Page column 120

35
[ 1393578-91-0 ]
[ 73870-24-3 ]
[ 1393577-91-7 ]

Yield	Reaction Conditions	Operation in experiment
25%	With hydrogenchloride; In methanol; at 20℃; for 0.0833333h;	Preparation of 6,7-dimethoxy-1-methyl-4-(pyridin-4-ylmethyl)isoquinolin-3-ol hydrochloride 11 To a solution of 6,7-dimethoxy-1-methylisoquinolin-3-ol CCH 18060 (197 mg, 899 mumol) in toluene (10 mL) in a 20 mL microwave vial equipped with a magnetic stirrer was added a 2 N aq. KOH solution (1.20 mL, 2.40 mmol) at RT followed by <strong>[73870-24-3]4-(bromomethyl)pyridine hydrobromide</strong> (250 mg, 988 mumol) and the mixture was stirred at 110 C. for 15 min under microwave irradiation. After cooling to RT, the mixture was diluted with H2O (5 mL) before extraction with CH2Cl2 (50 mL). The organic layer was washed with brine (10 mL), dried over Na2SO4, filtered and concentrated at 40 C. under vacuum. Purification by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 90:10) gave 70 mg of 6,7-dimethoxy-1-methyl-4-(pyridin-4-ylmethyl)isoquinolin-3-ol as a yellow solid. This free base was dissolved in MeOH (5 mL) in a 25 mL round-bottomed flask equipped with a magnetic stirrer before addition of a 0.15 M HCl solution in MeOH (7 mL). The reaction mixture was stirred for 5 min at RT and concentrated at 40 C. under vacuum to afford 6,7-dimethoxy-1-methyl-4-(pyridin-4-ylmethyl)isoquinolin-3-ol hydrochloride 11 as a yellow solid (78 mg, 25% yield). MW: 346.81; Yield: 25%; Yellow solid; Mp ( C.): 158.2 (dec.). Rf (free base): 0.2 (cyclohexane:EtOAc=75:25). 1H-NMR (DMSO d6, delta): 2.88 (s, 3H, CH3), 3.89 (s, 3H, OCH3), 3.91 (s, 3H, OCH3), 4.75 (s, 2H, CH2), 7.03 (s, 1H, ArH), 7.32 (s, 1H, ArH), 7.90 (d, 2H, J=6.4 Hz, 2ArH), 8.77 (d, 2H, J=6.4 Hz, 2ArH). 13C-NMR (DMSO d6, delta): 17.8, 30.5, 55.8, 56.2, 100.9, 105.0, 109.0, 116.2, 126.6 (2C), 137.5, 140.9 (2C), 148.0, 149.7, 154.1, 155.8, 161.2. MS-ESI m/z (rel.int.): 311 ([MH]+, 100).

Reference： [1]Patent: US2012/214837,2012,A1 .Location in patent: Page/Page column 30

36
[ 1415671-88-3 ]
[ 73870-24-3 ]
[ 1415672-25-1 ]

Yield	Reaction Conditions	Operation in experiment
60%		General procedure: A suspension of 2-(pyridin-3-ylamino)-4H-benz[e]-1,3-oxazin-4-one 10a-c (1 mmol) in 10 mL of dry acetonitrile in a 50 mL two necked round-bottomed flask was mixed with cesium carbonate (8.5 mmol) and refluxed for 2 h. 2-(bromomethyl)pyridine hydrobromide, 3-(chloromethyl)pyridine hydrochloride or <strong>[73870-24-3]4-(bromomethyl)-pyridine hydrobromide</strong> (2 mmol) in acetonitrile (10 mL) was added portion-wise. Upon completion of the addition, the reaction mixture was refluxed for a further 30 min then evaporated off under reduced pressure. The residue was washed with 4 × 15 mL of CHCl3 and then filtered. The CHCl3 filtrate was evaporated off under reduced pressure and the resulting residue was triturated with minimal amount of diethyl ether to give the crude solid which was recrystallized from an appropriate solvent. 2-(Pyridin-3-ylamino)-4H-benz[e]-1,3-oxazin-4-one 10a was allowed to react with <strong>[73870-24-3]4-(bromomethyl)pyridine hydrobromide</strong> according to general procedure C. The crude solid was collected and recrystallized from toluene to give 11g (60% yield), mp 234 C. numax (KBr) 3067, 2927 (C-H), 1680 (C=O), 1630 (C=C), 1554 (C=N) cm-1; 1H NMR (DMSO-d6) delta 8.56 (bd, Jmeta = 2.2 Hz, 1H, H-2'), 8.52 (d, J = 5 Hz, 2H, H-9', H-11'), 8.49 (bdd, JH4',H5' = 4.5 Hz, JH4',H2' = 1.5 Hz, 1H, H-4'), 8.17 (d, J = 7.5 Hz, 1H, H-5), 7.58 (d, J = 5 Hz, 2H, H-8', H-12'), 7.44 (t, J = 7.5 Hz, 1H, H-7), 7.40 (m, 1H, H-5'), 7.32 (d, J = 5 Hz, 1H, H-6'), 7.20 (t, J = 7.5 Hz, 1H, H-6), 6.70 (d, J = 7.5 Hz, 1H, H-8), 5.30 (s, 2H, CH2-N); 13C NMR (DMSO-d6) delta 165.0 (C-4), 155.2 (C-2), 151.5 (C-8a), 148.6 (C-9', 11'), 148.2 (C-2'), 148.0 (C-4'), 147.7 (C-4'), 144.7 (C-7'), 137.2 (C-1'), 135.3 (C-7), 126.1 (C-5', 6'), 124.5 (C-5/C-8), 123.5 (C-8, C-12'), 116.8 (C-4a), 53.7 (CH2-N); (Found C, 69.45; H, 4.76; N, 17.05; C19H14N4O2, requires C, 69.08; H, 4.27; N, 16.96).