Alternatived Products of [ 39891-12-8 ] Product Details of [ 39891-12-8 ]
| CAS No. : | 39891-12-8 | MDL No. : | MFCD00829308 |
| Formula : |
C7H6BrNO2 | Boiling Point : | - |
| Linear Structure Formula : | - | InChI Key : | UETIDNDXXGCJCE-UHFFFAOYSA-N |
| M.W : |
216.03
| Pubchem ID : | 2802539 |
| Synonyms : | |
Application In Synthesis of [ 39891-12-8 ]
* 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 [ 39891-12-8 ]
- 1
[ 39891-12-8 ]
[ 18107-18-1 ]
[ 118650-08-1 ]
| Yield | Reaction Conditions | Operation in experiment |
|---|
| 72% | In methanol; diethyl ether; toluene; at 20℃; for 0.166667h; | A 2.0 M solution of trimethylsilyldiazomethane in ether (10.3 mL, 20.5 mmol) was added dropwise to a solution of (5-bromo-pyridin-3-yl)-acetic acid (4.04 g, 18.7 mmol) in toluene (17.3 mL) and methanol (11.5 mL), and the mixture was stirred at room temperature for 10 minutes. The reaction solution was concentrated under reduced pressure. The residue was purified by silica gel chromatography (hexane:ethyl acetate = 1:3) to give the title compound (3.12 g, 72%). 1H-NMR (chloroform-d): 3.63 (2H, s), 3.73 (3H, s), 7.81 (1H, s), 8.44 (1H, s), 8.60 (1H, s). |
| | To a cooled (0 C) solution of (5-bromo-3-pyridinyl)acetic acid (1.00 g, 4.63 mmol) in diethyl ether (17 mL) and methanol (11 mL) was added a solution of(trimethylsilyl)diazomethane in diethyl ether (2.0 M, 4.6 ml, 9.3 mmol). The reaction was warmed to room temperature and then quenched by the dropwise addition of acetic acid. Once gas evolution ceased, the solution was concentrated under reduced pressure. The resulting material was diluted with ethyl acetate and washed with water and saturated aqueous sodium chloride solution. The organic layers were combined, dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification by flash chromatography on silica gel (20 - 80% ethyl acetate in hexanes) provided the title compound: LCMS m/z 231.66 [M + 2 + H]+; 1H NMR (500 MHz, CD3OD) delta 7.01 (s, 1 H), 6.88 (s, 1 H), 6.45 (s, 1 H), 2.21 (s, 2 H), 2.17 (s, 3 H). |
- 2
- [ 67-56-1 ]
- [ 39891-12-8 ]
- [ 118650-08-1 ]
| Yield | Reaction Conditions | Operation in experiment |
|---|
| 88% | With thionyl chloride;Reflux; | Compound 2-(5-bromopyridin-3-yl)acetic acid (1 ,15 g, 69.8 mmol) in MeOH (180 mL) was added SOCI2 (15 mL). The resulting mixture was refluxed overnight. After the reaction is completed, the volatile was removed in vaccuo. The residue was partitioned between ethyl acetate (100 mL) and water (20 mL). The organic layer was washed with saturated NaHCO3 (30 mL x 3), brine (20 mL x 2) and dried over Na2SO4. After filtration and evaporation of the solvent, 14g of A034-2 was obtained as a yellow solid in 88% yield. |
| 77% | With hydrogenchloride; In 1,4-dioxane; at 50℃; | Step 1 : 2-(5-bromopyridin-3-yl)acetic acid (500 mg, 2.31 mmol) was dissolved in MeOH (30 mL). HCI (4M in dioxane) (10 mL) was added and the mixture was heated overnight at 50 C. The mixture was concentrated to dryness. The oil was Ex.12a partitioned between EtOAc and sat. NaHCO3 solution. The organic layer was dried over MgSO4, filtered and the solution was concentrated to dryness. The resulting oil was purified by column chromatography on silica gel eluting with a gradient of Heptane/EtOAc from [100:0] to [50:50]. The product fractions were combined and concentrated to dryness to afford methyl 2-(5-bromopyridin-3- yl)acetate Ex.12a (412 mg, 77%) as colorless oil. |
| With thionyl chloride; at 0℃; for 2h; | To a suspension of 2-(5-bromopyridin-3~yl)acetic acid (5 g, 23.14 mmol) in MeOH (100 ml) was added thionyl chloride (1.858 mL, 25.5 mmol) at O 0C, and the mixture was stirred at O 0C for 2h. The mixture was concentrated in vacuo, re-dissolved in DCM (100 mL) and MeOH (10 mL), and saturated NaHCO3 in water (5 mL) was added, followed with NaHCO3 (10 g). To the mixture was added silica gel (10 g) and the mixture was concentrated. The residue was purified by silica chromatography eiuting with 0-50% EtOAc-heptane to give methyl 2-(5-bromopyridin-3-yl)acetate. 1H NMR (400 MHz, DMSO-dbeta) delta ppm 3.64 (s, 3 H), 3.80 (s, 2 H), 8.01 (dd, J=2.0 Hz. 1 H), 8.48 (d, J=1.8 Hz, 1 H), 8.61 (d, J-2.3 Hz, 1 H). |
| With thionyl chloride; at 0℃; for 2h;Inert atmosphere; Reflux; | To a solution of (5-bromo-pyridin-3-yl)-acetic acid (4.2 g, 20 mmol) in methanol (50 mL) was added thionyl chloride (4.4 mL, 60 mmol) slowly at 0C. After the addition, the reaction mixture was warmed up and heated to reflux temperature for 2 hours. After cooling back to room temperature, the reaction mixture was concentrated in vacuo and the residue was re-dissolved in EtOAc (250 mL) and washed with aq. NaHC03 solution and brine. The organic layer was dried over Na2S04, filtered and concentrated in vacuo to give a crude product (4.6 g, quant.) as light yellow solid. MS: 230.1 & 232.0 (M+H+). |
| With thionyl chloride; at 0℃; for 2h;Reflux; | [A] (5-Bromo-pyridin-3-yl)-acetic acid methyl ester To a solution of (5-bromo-pyridin-3-yl)-acetic acid (4.2 g, 20 mmol) in methanol (50 mL) was added thionyl chloride (4.4 mL, 60 mmol) slowly at 0 C. After the addition, the reaction mixture was warmed up and heated to reflux temperature for 2 hours. After cooling back to room temperature, the reaction mixture was concentrated in vacuo and the residue was re-dissolved in EtOAc (250 mL) and washed with aq. NaHCO3 solution and brine. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo to give a crude product (4.6 g, quant.) as light yellow solid. MS: 230.1 & 232.0 (M+H+). |
Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 1850 - 1864 [2]Patent: WO2014/154726,2014,A1 .Location in patent: Page/Page column 76 [3]Patent: WO2018/138356,2018,A1 .Location in patent: Page/Page column 35; 45 [4]Patent: WO2010/130796,2010,A1 .Location in patent: Page/Page column 113 [5]Patent: WO2013/79452,2013,A1 .Location in patent: Page/Page column 290 [6]Patent: US2013/143863,2013,A1 .Location in patent: Paragraph 1161; 1162 - 3
- ammoniacal methanol [ No CAS ]
[ 4045-25-4 ]- [ 39891-12-8 ]
- 1-[(5-Bromo-3-pyridinyl)acetyl]-4-methoxypiperidine [ No CAS ]
| Yield | Reaction Conditions | Operation in experiment |
|---|
| With diphenylphosphoranyl azide; triethylamine; In dichloromethane; N,N-dimethyl-formamide; | a) 1-[(5-Bromo-3-pyridinyl)acetyl]-4-methoxypiperidine A mixture of the 5-bromo-3-pyridine acetic acid (428 mg), <strong>[4045-25-4]4-methoxypiperidine hydrochloride</strong> (300 mg), triethylamine (826 mul), diphenylphosphoryl azide (640 mul), and DMF (10 ml) was stirred at +23 for 5 h. The mixture was evaporated, and the residual yellow oil was purified by column chromatography over silica gel eluding with a mixture of 5% ammoniacal methanol and dichloromethane (5:95) to give the product as a colourless gum. |
- 4
- [ 186581-53-3 ]
- [ 39891-12-8 ]
- [ 118650-08-1 ]
| Yield | Reaction Conditions | Operation in experiment |
|---|
| In methanol; at 20℃; for 0.0833333h; | To a solution of (5-bromopyridin-3-yl)acetic acid in methanol (0.1 M) was added a slight excess of a solution of diazomethane in ether at room temperature. After stirring for 5 min, solvents and residual diazomethane were removed under reduced pressure to afford the title compound |
- 5
[ 54648-79-2 ]- [ 39891-12-8 ]
- [ 118650-08-1 ]
| Yield | Reaction Conditions | Operation in experiment |
|---|
| | A solution of 3.0 g (13.8 mmol) of 5-bromo-3-pyridylacetic acid in 150 ml of THF was admixed with 3.3 g (30.8 mmol) of O-methyl-N,N'-diisopropylisourea. The reaction mixture was stirred at reflux temperature for 2 hours. For workup, tetrahydrofuran was removed under reduced pressure and the reaction mixture was admixed with ethyl acetate and washed with water and saturated aqueous sodium hydrogencarbonate solution. The organic phase was dried over magnesium sulphate and concentrated under reduced pressure. This gave 4.2 g of crude product in 74% yield (LC-MS), which was converted without further purifying operations. LC-MS (Method 1B): Rt=0.83 min; MS (ESIpos): m/z=231 [M+H]+. |
- 6
- [ 39891-12-8 ]
- [ 74-89-5 ]
- [ 118650-08-1 ]
Chemistry
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Material Science
