* 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.
Reference：
[1] Journal of Medicinal Chemistry, 2014, vol. 57, # 7, p. 2989 - 3004
2
[ 2999-46-4 ]
[ 405174-97-2 ]
[ 17288-32-3 ]
Reference：
[1] Journal of the Brazilian Chemical Society, 2011, vol. 22, # 11, p. 2036 - 2039
3
[ 405174-97-2 ]
[ 52378-64-0 ]
Yield
Reaction Conditions
Operation in experiment
99%
With sodium tetrahydroborate In tetrahydrofuran; methanol at 0 - 20℃; for 4 h;
(3-Bromopyridin-2-yl)methanol (B5.2) (0363) To a mixture of B5.1 (1 g, 5.4 mmol) in MeOH (20 mL) and THF (10 mL) was cooled to 0° C., NaBH4 (0.82 g, 21.6 mmol) was added in portions. The mixture was stirred for 4 h at rt. The mixture was concentrated, diluted with water (40 mL), extracted with DCM (40 mL×3), the organic layer was washed with brine, dried over Na2SO4, filtered and concentrated to give the title compound (1 g, 99percent) as a white solid. LC-MS: [M+H]+=190.0.
99%
With methanol; sodium tetrahydroborate In tetrahydrofuran at 0 - 20℃; for 4 h;
To a mixture of B5.1 (1 g, 5.4 mmol) in MeQH (20 mL) and THF (10 mL) was cooled to 0°C, NaBH4 (0.82 g, 21.6 mmol) wasadded in portions. The mixture was stirred for 4 h at it The mixture was concentrated, diluted with water (40 mL), extracted with DCM (40 mL x 3), the organic layer was washed with brine, dried over Na2SQ4, filtered and concentrated to give the title compound (1 g, 99percent) as a white solid. LC-MS: [M+H] = 190.0.
82%
With methanol; sodium tetrahydroborate In tetrahydrofuran at 0℃; for 4 h;
A mixture of B6.1 (480 mg, 2.58 mmol ) in MeOH(10 mL) and THF(5 mL) was cooled to 0 oC , NaBH4 (390 mg, 10.32 mmol) was added in portions .The mixture was stirred for 4 h, then concentrated, and diluted with water(30 mL), extracted with DCM (30 mL × 3). The organic layer was washed with brine (30 mL), dried over Na2SO4, concentrated to give the title compound (400 mg, 82percent) as a white solid. LC-MS: [MH]+ = 188.0.
With selenium(IV) oxide In 1,4-dioxane for 48 h; Reflux
Dissolve 3-bromo-2-methylpyridine (258 mg, 1.5 mmol) in dioxane (5 mL) and add selenium dioxide while stirring (666 mg, 6.0 mmol), the mixture was refluxed for 48 h, allowed to cool, and the filtrate was concentrated. The residue was purified by column chromatography to give a pale yellow solid. (175 mg, 63percent yield).
55%
With selenium(IV) oxide In 1,4-dioxane at 120℃; for 18 h;
3-Bromopicolinaldehyde (B5.1) (0362) A mixture of 3-bromo-2-methylpyridine (5 g, 29 mmol), SeO2 (17.5 mg, 116 mmol) in dioxane (70 mL) was heated to 120° C. and stirred for 18 h. The mixture was concentrated and purified by silica gel (PE:EA=4:1) to give the title compound (3 g, 55percent) as a white solid. LC-MS: [M+H]+=188.1.
55%
With selenium(IV) oxide In 1,4-dioxane at 120℃; for 18 h;
A mixture of 3-bromo-2-methylpyridine (5 g,2gmmol), SeQ2 (17.5 mg, ll6mmol) in dioxane (70 mL) was heated to 120°C andstirred for 18 h. The mixture was concentrated and purified by silica gel (PE:EA = 4:1)to give the title compound (3 g, 55percent) as a white solid. LC-MS: [M+H] = 188.1.
With selenium(IV) oxide; In 1,4-dioxane; for 48h;Reflux;
Dissolve 3-bromo-2-methylpyridine (258 mg, 1.5 mmol) in dioxane (5 mL) and add selenium dioxide while stirring (666 mg, 6.0 mmol), the mixture was refluxed for 48 h, allowed to cool, and the filtrate was concentrated. The residue was purified by column chromatography to give a pale yellow solid. (175 mg, 63% yield).
55%
With selenium(IV) oxide; In 1,4-dioxane; at 120℃; for 18h;
3-Bromopicolinaldehyde (B5.1) (0362) A mixture of 3-bromo-2-methylpyridine (5 g, 29 mmol), SeO2 (17.5 mg, 116 mmol) in dioxane (70 mL) was heated to 120 C. and stirred for 18 h. The mixture was concentrated and purified by silica gel (PE:EA=4:1) to give the title compound (3 g, 55%) as a white solid. LC-MS: [M+H]+=188.1.
55%
With selenium(IV) oxide; In 1,4-dioxane; at 120℃; for 18h;
A mixture of 3-bromo-2-methylpyridine (5 g,2gmmol), SeQ2 (17.5 mg, ll6mmol) in dioxane (70 mL) was heated to 120C andstirred for 18 h. The mixture was concentrated and purified by silica gel (PE:EA = 4:1)to give the title compound (3 g, 55%) as a white solid. LC-MS: [M+H] = 188.1.
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; 1,2-dimethoxyethane; at 90℃;
EXAMPLE 28 COMPOUND 28: N1-(3-methyl-pyridin-2-ylmethyl)-N1-(3-p-tolyl-pyridin-2-ylmethyl)-butane-1,4-diamine (HBr salt) To a stirred degassed solution of <strong>[405174-97-2]3-bromo-2-pyridinecarboxaldehyde</strong> (198 mg, 1.06 mmol) and 4-methylbenzene boronic acid (152 mg, 1.12 mmol) in DME/THF (3.5 mL, 2.5:1) were added a 2 M Na2CO3 solution (0.9 mL) and Pd(PPh3)4 (63 mg, 0.055 mmol). The reaction mixture was flushed with Ar and maintained under Ar while being heated at 90 C. overnight. The mixture was then cooled and diluted with EtOAc (40 mL) and brine (30 mL). The organic layer was washed with brine (1*30 mL), dried (Na2SO4), filtered and concentrated. Purification of the resultant oil by column chromatography with silica gel (Hexanes/EtOAc, 2:1) afforded 3-p-tolyl-pyridine-2-carbaldehyde (161 mg, 77%) as a yellow oil. 1H NMR (CDCl3) delta 2.43 (s, 3H), 7.25-7.28 (m, 4H), 7.53 (dd, 1H, J=9, 6 Hz), 7.79 (dd, 1H, J=9, 1 Hz), 8.80 (dd, J=3, 1 Hz), 10.09 (s, 1H).
EXAMPLE 10 COMPOUND 10: N1-(3-methyl-pyridin-2-ylmethyl)-N1-(3-thiophen-2-yl-pyridin-2-ylmethyl)-butane-1,4-diamine (HBr salt) A stirred solution of <strong>[405174-97-2]3-bromo-pyridine-2-carbaldehyde</strong> (126 mg, 0.675 mmol) and 2-thiopheneboronic acid (91.6 mg, 0.716 mmol) in a mixture of THF (0.75 mL), DME (2.0 mL) and 2M Na2CO3 (0.75 mL) was degassed with Ar for 15 minutes, after which Pd(PPh3)4 (39 mg, 0.034 mmol) was added and the heterogeneous mixture heated to 90 C. for 4 h. The reaction was quenched with brine (15 mL) and diluted with EtOAc (40 mL). The organic layer was separated, washed with brine (2*15 mL), dried (Na2SO4), filtered and concentrated in vacuo. Purification by flash chromatography on silica gel (Hexanes/EtOAc, 80:20) gave 3-thiophen-2-yl-pyridine-2-carbaldehyde (81 mg, 63%) as a yellow oil. 1H NMR (CDCl3) delta 7.13-7.22 (m, 2H), 7.48-7.57 (m, 2H), 7.92 (dd, 1H, J=7.9, 1.9 Hz), 8.82 (dd, 1H, J=6.0, 1.5 Hz), 10.23 (s, 1H).
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; 1,2-dimethoxyethane; at 90℃; for 16h;
EXAMPLE 67 COMPOUND 67: N1-[3-(3,5-Difluoro-phenyl)-pyridin-2-ylmethyl]-N1-(3,5-dimethyl-pyridin-2-ylmethyl)-butane-1,4-diamine HCl salt To a solution of <strong>[405174-97-2]3-bromo-pyridine-2-carbaldehyde</strong> (1.2 g, 6.45 mmol) dissolved in ethylene glycol dimethyl ether (25 mL), THF(10 mL) and saturated solution of Na2CO3 (9 mL) was added 3,5 difluorophenyl boronic acid (1.12 g, 7.10 mmol). Purge the mixture with Ar gas (10 min). To this mixture was added Pd(PPh3)4 (373 mg, 0.33 mmol) and stir under a positive pressure of Ar at 90 C. for 16 hours. The reaction mixture was quenched with a solution of saturated NaHCO3 (50 mL). Extract with CH2Cl2 (2*50 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated in vacuo to afford a light yellow oil. Purification via column chromatography on silica gel (CH2Cl2:MeOH: 80:20, v/v/v) afforded 3-(3,5-difluoro-phenyl)-pyridine-2-carbaldehyde as a white solid (0.86 g, 61%). 1H NMR (CDCl3) delta 6.59 (m, 1H), 6.92 (m, 2H), 7.60 (m, 1H), 7.76 (d, 1H, J=7.5 Hz), 8.88 (d, 1H, J=3.5 Hz), 10.11 (s, 1H).
With caesium carbonate;tris-(dibenzylideneacetone)dipalladium(0); In toluene; for 2h;Heating / reflux;
To a solution of 3-bromo-N-methoxy-N-methylpyridine-2-carboxamide (3-2; 219 mg, 0.89 mmole) in dry THF (4 mL) was added diisobutylaluminum hydride (0.94 mL, 0.94 mmole, 1M solution in CH2C12) slowly at -78 C. After 3 hr the mixture was quenched with IN HCI and stirred vigorously. After 4 hr the mixture was neutralized with 1M NaOH and extracted with CH2C12 (3x). The combined organic layers were dried (MgS04), filtered, and concentrated to give 3-bromopyridine-2- carboxaldehyde and its aminal with N,O-dimethylhydroxylamine as a mixture which was used in the next step without purification. (b) The mixture from (a) (134 mg, 0.72 mmole), phenyl acetamide (117 mg, 0.86 mmole), Cs2C03 (329 mg, 1.01 mmole), Pd2 (dba)3 (7 mg, 0.007 mmole), and xantphos (13 mg, 0.022 mmole) were combined in dry toluene (4 mL). The mixture was degassed (3 X pump/N2) then heated to reflux. After 2 hr the mixture was cooled, diluted with H20, and extracted with EtOAc (3x). The combined organic layers were dried (MgS04), filtered, and concentrated. Flash column (30% EtOAc/CHCl3) gave the title compound (3-4) as a pale yellow solid: IH-NMR (500 MHz, CDC13) 8 11.31 (bs, 1 H), 8.60 (m, 1 H), 8.19 (s, 1 H), 7.83 (m, 2 H), 7.65 (d, J = 8.06 Hz, 1 H), 7.53-7.27 (m, 4 H).
To a solution of 3-bromo-N-methoxy-N-methylpyridine-2-carboxamide (3-2; 219 mg, 0.89 mmole) in dry THF (4 mL) was added diisobutylaluminum hydride (0.94 mL, 0.94 mmole, 1M solution in CH2C12) slowly at -78 C. After 3 hr the mixture was quenched with IN HCI and stirred vigorously. After 4 hr the mixture was neutralized with 1M NaOH and extracted with CH2C12 (3x). The combined organic layers were dried (MgS04), filtered, and concentrated to give 3-bromopyridine-2- carboxaldehyde and its aminal with N,O-dimethylhydroxylamine as a mixture which was used in the next step without purification. (b) The mixture from (a) (134 mg, 0.72 mmole), phenyl acetamide (117 mg, 0.86 mmole), Cs2C03 (329 mg, 1.01 mmole), Pd2 (dba)3 (7 mg, 0.007 mmole), and xantphos (13 mg, 0.022 mmole) were combined in dry toluene (4 mL). The mixture was degassed (3 X pump/N2) then heated to reflux. After 2 hr the mixture was cooled, diluted with H20, and extracted with EtOAc (3x). The combined organic layers were dried (MgS04), filtered, and concentrated. Flash column (30% EtOAc/CHCl3) gave the title compound (3-4) as a pale yellow solid: IH-NMR (500 MHz, CDC13) 8 11.31 (bs, 1 H), 8.60 (m, 1 H), 8.19 (s, 1 H), 7.83 (m, 2 H), 7.65 (d, J = 8.06 Hz, 1 H), 7.53-7.27 (m, 4 H).
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; In N,N-dimethyl-formamide; at 20℃; for 1.5h;
A 50 mL reaction flask was charged with <strong>[405174-97-2]3-bromo-2-pyridinecarboxaldehyde</strong> (558 mg, 3 mmol). Bistriphenylphosphine dichloropalladium (105 mg, 0.15 mmol), cuprous iodide (29 mg, 0.15 mmol, 0.05 eq), Triethylamine (418 muL, 3 mmol) and trimethylsilylacetylene (768 muL, 5.4 mmol) were further added together with DMF (3 mL). The mixture was stirred at room temperature for 1.5 h and then diluted with ethyl acetate. The organic layer was washed with water and brine in that order and dried over anhydrous sodium sulfate. Concentration by filtration and column chromatography of the residue gave the title compound as a red oil (560 mg, 93% yield).
85%
With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; In N,N-dimethyl-formamide; at 20℃; for 1.5h;
A 50-mL, round-bottomed flask was charged with <strong>[405174-97-2]3-bromopicolinaldehyde</strong> (2.0 g, 10.6 mmol), dichlorobis(triphenylphosphine)palladium(II) (372 mg, 0.53 mmol), copper(I) iodide (101 mg, 0.53 mmol), and DMF (10 mL). The resulting suspension was treated with triethylamine (1.5 mL, 10.6 mmol), followed by (trimethylsilyl)acetylene (2.6 mL, 19.1 mmol). The reaction mixture was stirred at room temperature for 1.5 h and diluted with EtOAc. The organic layer was washed with water, brine, dried over Na2SO4; and concentrated in vacuo. The resulting residue was purified by silica gel chromatography (10-20% EtOAc in hexanes) to give 3-(2-(trimethylsilyl)ethynyl)picolinaldehyde (1.8 g, 85%) as a colorless oil. MS (ESI pos. ion) m/z: 204 (M+1).
Example 1; Synthesis of N-{ [3-(4-fluoro-2-methylphenvn-2-pyridinyl"|methyl) -5- isoquinolinamine; 1) N-[(3-Bromo-2-pyridinvOmethyl]-5-isoquinolinamine; To a solution of 3-bromo-2-pyridinecarboaldehyde (130 mg) in methanol (3.5 ml) was added 5-aminoisoquinoline (121 mg) and acetic acid (0.12 ml), and the reaction solution was stirred for 1 hour at room temperature. The reaction solution was cooled to 0C, and then sodium cyanoborohydride (67 mg) was added and stirring was conducted further for 1 hour at room temperature. The reaction solution was diluted with water, and extracted with ethyl acetate. The organic phases were combined, washed with water and a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resultant residue was purified by a silica gel chromatography (hexane:ethyl acetate=9: l to 8:2) to obtain the title compound (163 mg) as a yellow oil.
With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate; piperdinium acetate; In toluene; at 105℃; for 3h;Inert atmosphere;
The general procedure for the synthesis of the 3-aminoindolizine derivatives 1a-e, 6a-g, and uncyclized product 8a-c is described below: To a reaction mixture of cyano substrate 3 (2.0 mmol), 2-carbonyl pyridine derivative (2.0 mmol), and piperidinium acetate (15 mg, 0.10 mmol) in toluene (6 ml), was added diethyl 1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate (9) (Hantzsch ester, 557 mg, 2.2 mmol) in one portion at room temperature. The resulting mixture was degassed with a stream of nitrogen and then stirred at 105 C for 3 h. After cooling to room temperature, a minimum amount (ca 0.3-0.5 mL) of DMSO was added to the reaction mixture and the resulting solution was directly loaded to a silica gel column and purified by column chromatography using Teledyne Isco Combiflash system.
With hydroxylamine hydrochloride; triethylamine; In N,N-dimethyl-formamide; at 20℃; for 1h;
General procedure: To the mixture of 4-chlorobenzaldehyde (100 mg, 0.711 mmol) and hydroxylamine hydrochloride (49.4 mg, 0.711 mmol) in an 8-mL vial was added 1.5 mL of DMF, followed by the addition of triethylamine (0.099 mL, 0.711 mmol). The vial was capped and stirred at ambient temperature for 1 h. NCS (0.095 g, 0.711 mmol) was added and the reaction vial was capped and stirred at ambient temperature overnight. Additional 15 mg of NCS was added and the reaction continued for 6 h. A solution of (E)-ethyl 3-(pyrrolidin-1-yl)but-2-enoate (130 mg, 0.711 mmol) and triethylamine (0.059 mL, 0.427 mmol) in ethanol (0.9 mL) was added and the resulting reaction mixture was stirred at room temperature for 16 h. The product was purified by preparative HPLC (0.1% TFA, MeOH/H2O) to give 148.1 mg.
To a chilled (-78C) solution of D-1 (10 g, 54 mmol) in THF (150 mL) is added a solution of 3M MeMgBr in diethyl ether (35.8 mL, 108 mmol). The solution is stirred for 30 minutes at -78C and is allowed to warm to room temperature over 30 minutes. The reaction mixture is quenched with saturated NH4C1 and is extracted with EtOAc (3 x 100 mL). The combined organic layers are washed with brine (100 mL), dried over Na2SO4, filtered and concentrated to provide D-2.
(4-fluoro-phenyl)-hydrazine hydrochloride[ No CAS ]
[ 405174-97-2 ]
[ 1383734-81-3 ]
Yield
Reaction Conditions
Operation in experiment
With sodium acetate; In ethanol; water; at 50℃; for 18h;
To a solution of A-1 (2.50 g, 13.4 mmol) in EtOH (20 mL) and water (5 mL) is added A- 2 HC1 salt (2.38 g, 14.7 mmol) and sodium acetate (3.71 g, 27.3 mmol) in water (5 mL). The mixture is warmed to 50C. After 18 hours, the mixture is diluted with water (50 mL) and the solid is collected by filtration, washing with water and dried to provide A-3.
With sodium acetate; In ethanol; water; at 50℃; for 18h;
To a solution of A-1 (1.0 g, 5.4 mmol) in EtOH (10 mL) and water (2.5 mL) is added a solution of G-1 HC1 salt (0.89 g, 5.9 mmol) and sodium acetate (1.46 g, 5.91 mmol) in 5 mL of water and the mixture is warmed at 50C. After 18 hours, the mixture is diluted with water (50 mL) and extracted with EtOAc (2 x 100 mL). The combined organic layers are washed with brine (2 x 100 mL), dried over Na2SO4, filtered and concentrated to provide G-2.
With copper(II) sulfate; In dichloromethane; at 20℃;
Step 3. (S,E)-N-((3-Bromopyridin-2-yl)methylene)-2-methylpropane-2- sulflnamideA mixture of 3-bromo piconaldehyde (10 g, 53.8 mmol), copper sulfate (3.98 mL, 81 mmol) and (5)-2-methylpropane-2-sulfinamide (6.84 g, 56.4 mmol) in DCM (100 mL) was stirred at rt overnight. The solid was filtered off and the filtrate concentrated under vacuum. The residue thus obtained was purified by column chromatography using silica (100-200 mesh) with 20% EtOAc in n- hexane as eluent to give (S,E)-N-((3-bromopyridin-2-yl)methylene)-2- methylpropane-2-sulfinamide as yellow oil. 1H-NMR (400 MHz, CDC13): delta ppm 9.0 (s, 1H), 8.75 (d, 1H), 7.97 (d, 1H), 7.32 (t, 1H), 5.2 (d, 1H), 1.3 (s, 9H).
copper(II) sulfate; In dichloromethane; at 20℃;
Step 3. (S,E)-N-((3-Bromopyridin-2-yl)methylene)-2-methylpropane-2- sulflnamideA mixture of 3-bromo piconaldehyde (10 g, 53.8 mmol), copper sulfate (3.98 mL, 81 mmol) and (5)-2-methylpropane-2-sulfinamide (6.84 g, 56.4 mmol) in DCM (100 mL) was stirred at rt overnight. The solid was filtered off and the filtrate concentrated under vacuum. The residue was purified by column chromatography using silica (100-200 mesh) with 20% EtOAc in n-hexane as eluent to give (S,E)-N-((3-bromopyridin-2-yl)methylene)-2-methylpropane-2- sulfinamide as yellow oil. 1H-NMR (400 MHz, CDC13): 9.0(s, 1H), 8.74-8.76(d, 1H), 7.9-8.04(d, 1H), 7.26-7.38(t 1H), 5.2(d, 1H), 1.3(s, 9H).
With palladium diacetate; caesium carbonate; catacxium A; In 1,4-dioxane; at 140℃; for 1h;Microwave irradiation; Inert atmosphere;
General procedure: To a solution of 2-bromobenzaldehyde (1) (1.00 mmol) and phenylhydrazine (2) (1.00 mmol)in anhydrous 1,4-dioxane (2 mL) was added cesium carbonate (3.00 mmol) in a 2-5 mLcapacity microwave vial. The mixture was stirred and degassed with argon gas for 5 min. Tothis mixture were added Pd(OAc)2 (0.10 mmol) and di-1-adamantyl-n-butylphosphine (0.20mmol) under argon atmosphere, and purged with argon gas for 2 min and then molybdenumhexacarbonyl (2.50 mmol) was added and the vial was sealed and irradiated in microwave at140 C for 1 h. The vial was cooled to room temperature over a period of 10 min and filteredthrough Celite pad, washed with ethyl acetate (10 mL). The combined filtrate was concentrated in vacuo and the obtained residue was purified by flash column chromatography over 4 g SNAP cartridge by eluting with gradient of 20-40% ethyl acetate in hexane to afford2-phenylphthalazin-1(2H)-one (3) (60%).
With palladium diacetate; caesium carbonate; catacxium A; In 1,4-dioxane; at 140℃; for 1h;Microwave irradiation; Inert atmosphere;
General procedure: To a solution of 2-bromobenzaldehyde (1) (1.00 mmol) and phenylhydrazine (2) (1.00 mmol)in anhydrous 1,4-dioxane (2 mL) was added cesium carbonate (3.00 mmol) in a 2-5 mLcapacity microwave vial. The mixture was stirred and degassed with argon gas for 5 min. Tothis mixture were added Pd(OAc)2 (0.10 mmol) and di-1-adamantyl-n-butylphosphine (0.20mmol) under argon atmosphere, and purged with argon gas for 2 min and then molybdenumhexacarbonyl (2.50 mmol) was added and the vial was sealed and irradiated in microwave at140 C for 1 h. The vial was cooled to room temperature over a period of 10 min and filteredthrough Celite pad, washed with ethyl acetate (10 mL). The combined filtrate was concentrated in vacuo and the obtained residue was purified by flash column chromatography over 4 g SNAP cartridge by eluting with gradient of 20-40% ethyl acetate in hexane to afford2-phenylphthalazin-1(2H)-one (3) (60%).
With palladium diacetate; caesium carbonate; catacxium A; In 1,4-dioxane; at 140℃; for 1h;Microwave irradiation; Inert atmosphere;
General procedure: To a solution of 2-bromobenzaldehyde (1) (1.00 mmol) and phenylhydrazine (2) (1.00 mmol)in anhydrous 1,4-dioxane (2 mL) was added cesium carbonate (3.00 mmol) in a 2-5 mLcapacity microwave vial. The mixture was stirred and degassed with argon gas for 5 min. Tothis mixture were added Pd(OAc)2 (0.10 mmol) and di-1-adamantyl-n-butylphosphine (0.20mmol) under argon atmosphere, and purged with argon gas for 2 min and then molybdenumhexacarbonyl (2.50 mmol) was added and the vial was sealed and irradiated in microwave at140 C for 1 h. The vial was cooled to room temperature over a period of 10 min and filteredthrough Celite pad, washed with ethyl acetate (10 mL). The combined filtrate was concentrated in vacuo and the obtained residue was purified by flash column chromatography over 4 g SNAP cartridge by eluting with gradient of 20-40% ethyl acetate in hexane to afford2-phenylphthalazin-1(2H)-one (3) (60%).
With palladium diacetate; caesium carbonate; catacxium A; In 1,4-dioxane; at 140℃; for 1h;Microwave irradiation; Inert atmosphere;
General procedure: To a solution of 2-bromobenzaldehyde (1) (1.00 mmol) and phenylhydrazine (2) (1.00 mmol)in anhydrous 1,4-dioxane (2 mL) was added cesium carbonate (3.00 mmol) in a 2-5 mLcapacity microwave vial. The mixture was stirred and degassed with argon gas for 5 min. Tothis mixture were added Pd(OAc)2 (0.10 mmol) and di-1-adamantyl-n-butylphosphine (0.20mmol) under argon atmosphere, and purged with argon gas for 2 min and then molybdenumhexacarbonyl (2.50 mmol) was added and the vial was sealed and irradiated in microwave at140 C for 1 h. The vial was cooled to room temperature over a period of 10 min and filteredthrough Celite pad, washed with ethyl acetate (10 mL). The combined filtrate was concentrated in vacuo and the obtained residue was purified by flash column chromatography over 4 g SNAP cartridge by eluting with gradient of 20-40% ethyl acetate in hexane to afford2-phenylphthalazin-1(2H)-one (3) (60%).
3-(4-methoxyphenyl)-2-pyridinecarboxaldehyde[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
2 g
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,2-dimethoxyethane; water; for 2h;Reflux; Inert atmosphere;
A suspension of <strong>[405174-97-2]3-bromopicolinaldehyde</strong> (13 A, 1.86 g, 10 mmol), potassium carbonate (50ml, 2M in water), 4-methoxyphenylboronic acid (1.6g, 10.5 mmol) and tetrakis(triphenylphosphine) palladium (580 mg, 0.5 mmol) in DME (70 ml) was degassed for 30 minutes. The mixture was heated at reflux for 2 hours. The reaction was cooled and filtered through celite. The filtrate was extracted with EtOAc (2x50 ml). The organic layer was dried over Na2S04, filtered and concentrated. The crude product was purified by flash column (Rf: 0.4 50 % EtOAc/Hexanes). The yield was 2g. MS (m/z) 214 [M+H]+
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