Alternatived Products of [ 136866-39-2 ]
Product Details of [ 136866-39-2 ]
CAS No. : | 136866-39-2 |
MDL No. : | MFCD15526910 |
Formula : |
C6H4Cl2N2O
|
Boiling Point : |
- |
Linear Structure Formula : | - |
InChI Key : | IPYUCBQERMHHCU-UHFFFAOYSA-N |
M.W : |
191.01
|
Pubchem ID : | 15696851 |
Synonyms : |
|
Safety of [ 136866-39-2 ]
Application In Synthesis of [ 136866-39-2 ]
* 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 [ 136866-39-2 ]
- 1
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[ 136866-39-2 ]
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[ 380430-49-9 ]
-
[ 1426214-81-4 ]
Yield | Reaction Conditions | Operation in experiment |
61% |
With palladium bis[bis(diphenylphosphino)ferrocene] dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 1h; |
1-(3,5-Dichloro-pyrazin-2-yl)-ethanone (2.2 g), prepared as described in example 10, and (4-tert-butoxycarbonyl-aminophenyl)boronic acid (2.7 g), was added to a reaction vessel containing a magnetic stirring bar together with 1,1'-bis(diphenylphosphino)ferrocene-palladium(ll) dichloride (674 mg) and cesium carbonate (11 .2 g), followed by 100 ml dioxane and 10 ml water, and the mixture heated to 100 C under stirring. After 1 h the reaction mixture was cooled to RT and quenched with a saturated aqueous sodium bicarbonate solution (50 ml) and extracted with EtOAc (3 x 100 ml). The combined organic phases were dried over sodium sulfate, filtered and evaporated to afford the crude product as a dark brown oil. Purification by flash chromatography on silica gel using a mixture of EtOAc and heptane as the eluent afforded [4-(5-acetyl-6-chloro-pyrazin-2-yl)-phenyl]-carbamic acid tert-butyl ester as a colorless solid after evaporation of the solvents under reduced pressure. Yield: 2.44 g (61 %). |
61% |
With palladium bis[bis(diphenylphosphino)ferrocene] dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 1h; |
1-(3,5-Dichloro-pyrazin-2-yl)-ethanone (2.2 g), prepared as described in example 10, and (4-tert-butoxycarbonyl-aminophenyl)boronic acid (2.7 g), was added to a reaction vessel containing a magnetic stirring bar together with 1,1'- bis(diphenylphosphino)ferrocene-palladium(ll) dichloride (674 mg) and cesium carbonate (11 .2 g), followed by 100 ml dioxane and 10 ml water, and the mixture heated to 100C under stirring. After 1 h the reaction mixture was cooled to RT and quenched with a saturated aqueous sodium bicarbonate solution (50 ml) and extracted with EtOAc (3 x 100 ml). The combined organic phases were dried over sodium sulfate, filtered and evaporated to afford the crude product as a dark brown oil. Purification by flash chromatography on silica gel using a mixture of EtOAc and heptane as the eluent afforded [4-(5-acetyl-6-chloro-pyrazin-2-yl)-phenyl]-carbamic acid tert-butyl ester as a colorless solid after evaporation of the solvents under reduced pressure. Yield: 2.44g (61 %) mg |
61% |
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 1h; |
(i) [4-(5-Acetyl-6-chloro-pyrazin-2-yl)-phenyl]-carbamic acid tert-butyl ester 1-(3,5-Dichloro-pyrazin-2-yl)-ethanone (2.2 g), prepared as described in example 10, and (4-tert-butoxycarbonyl-aminophenyl)boronic acid (2.7 g), was added to a reaction vessel containing a magnetic stirring bar together with 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) dichloride (674 mg) and cesium carbonate (11.2 g), followed by 100 ml dioxane and 10 ml water, and the mixture heated to 100 C. under stirring. After 1 h the reaction mixture was cooled to RT and quenched with a saturated aqueous sodium bicarbonate solution (50 ml) and extracted with EtOAc (3*100 ml). The combined organic phases were dried over sodium sulfate, filtered and evaporated to afford the crude product as a dark brown oil. Purification by flash chromatography on silica gel using a mixture of EtOAc and heptane as the eluent afforded [4-(5-acetyl-6-chloro-pyrazin-2-yl)-phenyl]-carbamic acid tert-butyl ester as a colorless solid after evaporation of the solvents under reduced pressure. Yield: 2.44 g (61%) mg. |
61% |
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100℃; for 1h; |
According to an embodiment 10 of the preparation described in 1-(3,5-dichloro-pyrazine-2-yl)-ethanone (2.2g) and (4-tert-butoxy carbonyl-aminophenyl) boric acid (2.7g) adding to the containing magnetic stirring rod and 1, the 1,1'-bis(diphenylphosphino)ferrocene palladium dichloride (674 mg) and cesium carbonate (11.2g) in the reaction container, subsequently joined 100 ml dioxane and 10 ml of water, the mixture is heated under stirring to 100 C. 1h reaction mixture after cooling to the room temperature and with the saturated aqueous solution of sodium bicarbonate (50 ml) for quenching and EtOAc (3×100 ml) extraction. The combined organic phase is dried with sodium sulfate, filtered and evaporation to obtain dark brown oily crude product. Fast by silica gel chromatography using EtOAc and heptane mixture of purification as an eluent, obtained after evaporation of the solvent under reduced pressure to the colorless solid [4 - (5-acetyl-6-chloro-pyrazin-2-yl)-phenyl]-amino- formic acid uncle contact. Yield: 2.44g (61%). |
61% |
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; water; at 100℃; for 1h; |
(3,5-dichloro-pyrrazin-2-yl)-ethanone (2.2 g) prepared as described in Example 10 (2.2 g) and (4-tert-butoxycarbonyl-aminophenyl) boronic acid(2.7 g) was added to a solution of 1,1'-bis (diphenylphosphino) ferrocene-paradium (II) dicloride (674 mg) and sodium carbonate (11.2 g), followed by addition of 100 ml of dioxane and 10 ml of water, and the mixture was heated to 100 C. under stirring.After 1 h the reaction mixture was cooled to room temperature and quenched with saturated aqueous sodium bicarbonate solution (50 ml) and extracted with EtOAc (3 × 100 ml). The combined organic phases were dried over sodium sulfate, filtered and evaporated to give the crude product as a thick brown oil. After purification by flash chromatography on silica gel using a mixture of EtOAc and heptane as eluent and evaporation of the solvent under reduced pressure, [4- (5-acetyl-6-chloro-pyrazin-2 - yl) -phenyl] -carbamic acid tert-butyl ester. Yield: 2.44 g (61%) |
Reference:
[1]Patent: WO2013/41502,2013,A1 .Location in patent: Page/Page column 96; 97
[2]Patent: WO2013/41119,2013,A1 .Location in patent: Page/Page column 95; 96
[3]Patent: US2013/72493,2013,A1 .Location in patent: Paragraph 0339
[4]ACS Medicinal Chemistry Letters,2015,vol. 6,p. 73 - 78
[5]Patent: CN103012407,2016,B .Location in patent: Paragraph 0363; 0365; 0366
[6]Patent: JP5827849,2015,B2 .Location in patent: Paragraph 0141
- 2
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[ 312736-50-8 ]
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[ 136866-39-2 ]
- 3
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[ 313339-92-3 ]
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[ 75-16-1 ]
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[ 136866-39-2 ]
Yield | Reaction Conditions | Operation in experiment |
99% |
In diethyl ether; at -78 - 20℃; for 1h; |
107281 3,5-Dichloropyrazine-2-carbonitrile (Example 12, Step 2, 31.0 g, 178.18 mmol) was dissolved in anhydrous diethyl ether (890 mL, 0.2 M) and cooled to -78 C. Then MeMgBr indiethyl ether (3.0 M, 65.3 mL, 190 mmol) was added slowly to maintain low temperature. After the addition was complete, the mixture was slowly warmed room temperature and stirred at room temperature for 1 h. The mixture was poured into a beaker containing a mixture of HC1 in water (1.0 M, 1 L) and ice (1 kg). The mixture was stirred vigorously for 10 mm. The mixture was extracted with diethyl ether (3 X 1 L). The combined organic layers were dried over Na2504 andconcentrated under reduced pressure to afford the title compound as an orange oil (34 g, 99% yield). The mixture was used for the next reaction without further purification. ?H NMR (400 IVIHz, CDC13): ppm 8.56 (s, 1H), 2.71 (s, 3H). |
99% |
In diethyl ether; at -78 - 20℃; for 1h; |
3,5-Dichloropyrazine-2-carbonitrile (Example 12, Step 2, 31.0 g, 178.18 mmol) was dissolved in anhydrous diethyl ether (890 mL, 0.2M) and cooled to -78 C. Then MeMgBr in diethyl ether (3.0 M, 65.33 mL, 190.0 mmol) was added slowly to maintain low temperature. After the addition was complete, the mixture was slowly warmed room temperature and stirred 1 h. The mixture was poured into a beaker containing a mixture of HCl in water (1.0 M, 1 L) and ice (1 kg). The mixture was stirred vigorously for 10 min. The mixture was extracted with diethyl ether (3*1 L), the combined organic layers were dried over sodium sulfate and concentrated under reduced pressure to afford the title compound as an orange oil (34 g, 99% yield). The mixture was used for the next reaction without further purification. |
- 4
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[ 136866-39-2 ]
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[ 1314936-02-1 ]
Yield | Reaction Conditions | Operation in experiment |
91.4% |
With triethylsilane; boron trifluoride diethyl etherate In acetonitrile at 0 - 20℃; for 3h; |
1.4; 2.4; 3.4 Step 4:
Add 150g of 3,5-dichloro-2-acetylpyrazine obtained in step 3 and 1L of acetonitrile, start cooling to 0°C, add 14.9ml of boron trifluoride ether, and dropwise add 182.2g of triethyl Silane was stirred at room temperature for 3 hours and the solvent was removed to obtain 127 g of unpurified 3,5-dichloro-2-ethylpyrazine with a yield of 91.4%. |