Home Cart 0 Sign in  

[ CAS No. 127-19-5 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
HazMat Fee +

There will be a HazMat fee per item when shipping a dangerous goods. The HazMat fee will be charged to your UPS/DHL/FedEx collect account or added to the invoice unless the package is shipped via Ground service. Ship by air in Excepted Quantity (each bottle), which is up to 1g/1mL for class 6.1 packing group I or II, and up to 25g/25ml for all other HazMat items.

Type HazMat fee for 500 gram (Estimated)
Excepted Quantity USD 0.00
Limited Quantity USD 15-60
Inaccessible (Haz class 6.1), Domestic USD 80+
Inaccessible (Haz class 6.1), International USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic USD 100+
Accessible (Haz class 3, 4, 5 or 8), International USD 200+
Chemical Structure| 127-19-5
Chemical Structure| 127-19-5
Structure of 127-19-5 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 127-19-5 ]

Related Doc. of [ 127-19-5 ]

Alternatived Products of [ 127-19-5 ]

Product Details of [ 127-19-5 ]

CAS No. :127-19-5 MDL No. :MFCD00008686
Formula : C4H9NO Boiling Point : -
Linear Structure Formula :- InChI Key :FXHOOIRPVKKKFG-UHFFFAOYSA-N
M.W :87.12 Pubchem ID :31374
Synonyms :
N,N-Dimethylacetamide

Calculated chemistry of [ 127-19-5 ]

Physicochemical Properties

Num. heavy atoms : 6
Num. arom. heavy atoms : 0
Fraction Csp3 : 0.75
Num. rotatable bonds : 1
Num. H-bond acceptors : 1.0
Num. H-bond donors : 0.0
Molar Refractivity : 24.44
TPSA : 20.31 Ų

Pharmacokinetics

GI absorption : Low
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -7.38 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.46
Log Po/w (XLOGP3) : -0.77
Log Po/w (WLOGP) : 0.09
Log Po/w (MLOGP) : 0.08
Log Po/w (SILICOS-IT) : -0.48
Consensus Log Po/w : 0.08

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 2.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : 0.17
Solubility : 129.0 mg/ml ; 1.48 mol/l
Class : Highly soluble
Log S (Ali) : 0.82
Solubility : 577.0 mg/ml ; 6.63 mol/l
Class : Highly soluble
Log S (SILICOS-IT) : -0.22
Solubility : 52.1 mg/ml ; 0.598 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.0

Safety of [ 127-19-5 ]

Signal Word:Danger Class:9
Precautionary Statements:P201-P202-P210-P264-P273-P280-P302+P352-P305+P351+P338-P312-P332+P313-P337+P313-P391-P405-P501 UN#:3082
Hazard Statements:H227-H302-H315-H319-H360-H410 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 127-19-5 ]

* 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.

  • Upstream synthesis route of [ 127-19-5 ]
  • Downstream synthetic route of [ 127-19-5 ]

[ 127-19-5 ] Synthesis Path-Upstream   1~57

  • 1
  • [ 5315-25-3 ]
  • [ 127-19-5 ]
  • [ 6940-57-4 ]
Reference: [1] Journal of the Chemical Society - Dalton Transactions, 1999, # 3, p. 349 - 355
[2] Journal of the American Chemical Society, 1997, vol. 119, # 24, p. 5606 - 5617
[3] Journal of Organic Chemistry, 1998, vol. 63, # 8, p. 2481 - 2487
  • 2
  • [ 4926-28-7 ]
  • [ 127-19-5 ]
  • [ 59576-26-0 ]
YieldReaction ConditionsOperation in experiment
59%
Stage #1: With n-butyllithium In diethyl ether; hexane at -78℃; for 0.166667 - 0.5 h;
Stage #2: at 20℃; for 2 - 14.5 h;
[Referential Example 16] 1-(6-Methoxy-3-pyridazinyl)-5-(4-methyl-2-pyridyl)-1H-pyrazole-3-carboxylic acid; [Show Image] 1) 1-(4-methyl-2-pyridyl)ethanone; A 1.58M solution of n-butyllithium in hexane (17 ml) was added dropwise over 10 minutes to a solution of 2-bromo-4-picoline (3.0 g) in diethylether (45 ml) at -78°C, and the solution was stirred for 20 minutes. N,N-dimethyl acetamide (2.5 ml) was added dropwise to the reaction liquid, and the temperature of the reaction liquid was gradually elevated to room temperature, and the mixture was stirred for 2 hours. Water and ethyl acetate were added to the reaction liquid and the phases were separated, and the organic layer was dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography on silica gel (hexane-ethyl acetate) to give 1-(4-methyl-2-pyridyl)ethanone (1.64 g, 70percent) as an oily product. 1H-NMR (400 MHz, CDCl3)δ: 2.38 (3H, s), 2.66 (3H, s), 7.23 (1H, dd, J = 4.88, 0.86 Hz), 7.81 (1H, d, J = 0.86 Hz), 8.48 (1H, d, J = 4.88 Hz).; [Referential Example 29] 5-(4-Hydroxymethyl-2-pyridyl)-1-(6-methoxy -3-pyridyl)-1H-pyrazole-3-carboxylic acid; [Show Image] 1) 2-acetyl-4-methylpyridine; A 1.58M solution of n-butyllithium in hexane (22 ml) was added dropwise to a solution of 2-bromo-4-picoline (4 g) in diethylether (60 ml) over 5 minutes at -78°C, and the mixture was stirred for 5 minutes. N,N-dimethyl acetamide (3.3 ml) was added dropwise to the reaction liquid, and the mixture was stirred at room temperature for 14.5 hours. Water and ethyl acetate were added to the reaction liquid and the phases were separated, and the organic layer was dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography on silica gel (hexane-ethyl acetate) to give 2-acetyl-4-methylpyridine (1.86 g, 59percent) as an oily product. 1H-NMR (400 MHz, CDCl3)δ: 2.42 (3H, s), 2.72 (3H, s), 7.29 (1H, dd, J = 4.94, 0.67 Hz), 7.86 (1H, d, J = 0.67 Hz), 8.54 (1H, d, J = 4.94 Hz).
59%
Stage #1: With n-butyllithium In diethyl ether; hexane at -78℃; for 0.166667 h;
Stage #2: at 20℃; for 14.5 h;
1) 1-(4-Methyl-2-pyridyl)-1-ethanone Under cooling to -78°C, n-butyllithium (a 1.58 M solution in hexane, 22 mL) was added dropwise to a solution of 2-bromo-4-picoline (4.0 g) in diethyl ether (60 mL) over 5 minutes, and then the resultant mixture was stirred for 5 minutes. N, N-Dimethyl acetamide (3.3 mL) was added dropwise to the reaction solution, and the mixture was gradually warmed to room temperature, and stirred for 14.5 hours. Water was added to the reaction solution, which was then extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate. After separation by filtration, a residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (ethyl acetate-hexane), to obtain 1-(4-methyl-2-pyridyl)-1-ethanone (1.86 g, 59percent) as an oily product. 1H-NMR(400MHz, CDCl3)δ: 2.42(3H, s), 2.72(3H, s), 7.29(1H, dd, J=4.94, 0.67Hz), 7.86(1H, d, J=0.67Hz), 8.54(1H, d, J=4.94Hz).
Reference: [1] Patent: EP1698626, 2006, A1, . Location in patent: Page/Page column 34; 44
[2] Patent: EP1785418, 2007, A1, . Location in patent: Page/Page column 58
[3] Journal of the American Chemical Society, 1997, vol. 119, # 24, p. 5606 - 5617
  • 3
  • [ 109-06-8 ]
  • [ 127-19-5 ]
  • [ 6302-02-9 ]
Reference: [1] Journal of the Chemical Society - Perkin Transactions 1, 1998, # 22, p. 3807 - 3812
  • 4
  • [ 109-06-8 ]
  • [ 127-19-5 ]
  • [ 107-13-1 ]
  • [ 6302-02-9 ]
  • [ 100060-06-8 ]
  • [ 100714-41-8 ]
Reference: [1] Journal of the Chemical Society - Perkin Transactions 1, 1998, # 22, p. 3807 - 3812
[2] Journal of the Chemical Society - Perkin Transactions 1, 1998, # 22, p. 3807 - 3812
  • 5
  • [ 96-54-8 ]
  • [ 127-19-5 ]
  • [ 932-16-1 ]
Reference: [1] Journal of the Indian Chemical Society, 2005, vol. 82, # 11, p. 1019 - 1021
  • 6
  • [ 127-19-5 ]
  • [ 31183-89-8 ]
  • [ 2942-10-1 ]
Reference: [1] Chemical Communications, 2011, vol. 47, # 48, p. 12867 - 12869
  • 7
  • [ 10075-50-0 ]
  • [ 127-19-5 ]
  • [ 53330-94-2 ]
Reference: [1] Heterocycles, 1992, vol. 34, # 6, p. 1169 - 1175
  • 8
  • [ 127-19-5 ]
  • [ 6134-79-8 ]
  • [ 5078-07-9 ]
Reference: [1] Organic Process Research and Development, 2010, vol. 14, # 1, p. 72 - 84
  • 9
  • [ 127-19-5 ]
  • [ 7732-36-7 ]
  • [ 2942-13-4 ]
Reference: [1] Chemical Communications, 2011, vol. 47, # 48, p. 12867 - 12869
  • 10
  • [ 5348-42-5 ]
  • [ 127-19-5 ]
  • [ 6478-79-1 ]
YieldReaction ConditionsOperation in experiment
69% With Imidazole hydrochloride In 5,5-dimethyl-1,3-cyclohexadieneHeating General procedure: A mixture of 1a (0.54 g, 5 mmol), imidazolium chloride (0.09 g, 0.5 mmol) and N, N-dimethylbenzamide (0.55 g, 7.5 mmol) in 5mL xylene was heated to 140 °C and stirred at this temperature for 8 h. When the reaction was completed, 50mL water was added and the resulting mixture was extracted with 50 mL ethyl acetate twice. The combined organic layer was successively washed with H2O (50 mL) and then brine (50 mL), then dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel using petroleum ether and ethyl acetate as the eluent or recrystallized from petroleum ether/EA to give the desired products.
Reference: [1] Tetrahedron, 2018, vol. 74, # 52, p. 7450 - 7456
  • 11
  • [ 127-19-5 ]
  • [ 575433-20-4 ]
  • [ 442-51-3 ]
Reference: [1] Tetrahedron, 2004, vol. 60, # 25, p. 5315 - 5318
  • 12
  • [ 127-19-5 ]
  • [ 108-95-2 ]
  • [ 2524-64-3 ]
Reference: [1] Patent: US6613848, 2003, B1,
  • 13
  • [ 62208-67-7 ]
  • [ 127-19-5 ]
  • [ 39786-40-8 ]
Reference: [1] Journal of Heterocyclic Chemistry, 1991, vol. 28, # 2, p. 263 - 267
  • 14
  • [ 127-19-5 ]
  • [ 98-86-2 ]
  • [ 1201-93-0 ]
Reference: [1] Patent: WO2018/17874, 2018, A1, . Location in patent: Page/Page column 57
  • 15
  • [ 67-56-1 ]
  • [ 127-19-5 ]
  • [ 18871-66-4 ]
Reference: [1] Tetrahedron Letters, 2002, vol. 43, # 43, p. 7757 - 7759
[2] Journal of Chemical Research, 2011, vol. 35, # 2, p. 119 - 120
  • 16
  • [ 127-19-5 ]
  • [ 124-41-4 ]
  • [ 77-78-1 ]
  • [ 18871-66-4 ]
Reference: [1] Chinese Chemical Letters, 2010, vol. 21, # 2, p. 163 - 166
  • 17
  • [ 127-19-5 ]
  • [ 3315-60-4 ]
  • [ 77-78-1 ]
  • [ 18871-66-4 ]
Reference: [1] Collection of Czechoslovak Chemical Communications, 1986, vol. 51, # 9, p. 1964 - 1971
  • 18
  • [ 626-05-1 ]
  • [ 127-19-5 ]
  • [ 49669-13-8 ]
YieldReaction ConditionsOperation in experiment
81%
Stage #1: With n-butyllithium In diethyl ether; hexane at -78℃; for 0.5 h; Inert atmosphere
Stage #2: at -78℃; for 3 h;
2,6-dibromopyridine (10.0 g, 42.2 mmol) was placed in a reaction flask. To ensure a nitrogen atmosphere in the reaction flask, the gas in the reaction flask was drawn out and the reaction flask was refilled with nitrogen gas in a rapid manner three times. To the reaction flask, 150 ml of anhydrous diethylether was added, and then 17.7 ml of an n-butyllithium solution (44.3 mmol, 2.5 M in n-hexane) was slowly added at −78° C. to obtain a mixture. In the meanwhile, the color of the mixture changed from transparent to yellowish-brown. The mixture in the reaction flask was kept at −78° C. and continuously stirred for 30 minutes. Then, N,N-dimethylacetamide (4.7 ml, 50.7 mmol) was slowly added to the mixture, and the mixture was kept at −78° C. for 3 hours for reaction. Thereafter, the temperature of the mixture was slowly raised to 20° C. At this moment, the color of the mixture in the reaction flask changed to cloudy gray. Deionized water was slowly added to the mixture to terminate the reaction in the reaction flask. The solvents in the mixture were drawn out of the reaction flask, and the residue in the reaction flask was washed several times with ethyl acetate and with a saturated sodium chloride solution to collect an organic layer, followed by dehydration of the organic layer using sodium sulfate (Na2SO4) to thereby obtain a crude product. The crude product was subjected to column chromatography (SiO2, ethyl acetate:n-hexane=1:20), followed by recrystallization in a mixed solvent having dichloromethane and n-hexane (dichloromethane:n-hexane=1:20) at 20° C., thereby obtaining white crystals (6.80 g, 81percent yield). (0046) The spectrum analysis for the white crystals is: 1H NMR (400 MHz, CDCl3): δ 7.97 (dd, J=7.0, 1.6 Hz, 1H), 7.68 (t, J=7.8 Hz, 1H), 7.64 (dd, J=8.0, 1.2 Hz, 1H), 2.69 (s, 3H). The white crystals were confirmed to be Compound L1-1 having a chemical structure represented by
Reference: [1] Organometallics, 2016, vol. 35, # 2, p. 198 - 206
[2] Journal of Heterocyclic Chemistry, 2009, vol. 46, # 1, p. 116 - 118
[3] Patent: US9219237, 2015, B1, . Location in patent: Page/Page column 7
[4] Journal of Organic Chemistry, 2006, vol. 71, # 1, p. 167 - 175
[5] Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 24, p. 6763 - 6770
[6] Journal of Organic Chemistry, 1997, vol. 62, # 23, p. 8237 - 8239
[7] Tetrahedron Asymmetry, 2000, vol. 11, # 21, p. 4341 - 4357
[8] Nucleosides and Nucleotides, 1999, vol. 18, # 6-7, p. 1657 - 1658
[9] Inorganic Chemistry, 2014, vol. 53, # 11, p. 5788 - 5796
[10] Chemische Berichte, 1992, vol. 125, # 5, p. 1169 - 1190
[11] Tetrahedron Letters, 1994, vol. 35, # 43, p. 7973 - 7976
[12] Journal of Organic Chemistry, 1998, vol. 63, # 8, p. 2481 - 2487
[13] Tetrahedron Letters, 2001, vol. 42, # 4, p. 659 - 662
[14] Tetrahedron Letters, 2003, vol. 44, # 33, p. 6305 - 6307
[15] Journal of Organometallic Chemistry, 2004, vol. 689, # 8, p. 1356 - 1361
[16] Organic and Biomolecular Chemistry, 2003, vol. 1, # 11, p. 1894 - 1899
[17] Patent: WO2009/77990, 2009, A1, . Location in patent: Page/Page column 76
[18] Dalton Transactions, 2012, vol. 41, # 6, p. 1792 - 1800
[19] Synlett, 2013, vol. 24, # 19, p. 2555 - 2558
  • 19
  • [ 40473-07-2 ]
  • [ 127-19-5 ]
  • [ 21190-93-2 ]
Reference: [1] ChemPlusChem, 2016, vol. 81, # 10, p. 1123 - 1128
  • 20
  • [ 3510-66-5 ]
  • [ 127-19-5 ]
  • [ 5308-63-4 ]
YieldReaction ConditionsOperation in experiment
87%
Stage #1: With n-butyllithium In diethyl ether; hexane at -78℃; for 0.166667 h;
Stage #2: at -78℃; for 2 h;
[Referential Example 35] 5-(5-Methyl-2-pyridyl)-1-(2-pyridyl)-1H-pyrazole-3-carboxylic acid; [Show Image] 1) 1-(5-Methyl-2-pyridyl)ethanone; n-Butyllithium (1.58M solution in hexane, 24 ml) was added to a solution of 2-bromo-5-picoline (5.0 g) in diethylether (100 ml) in 5 minutes at -78°C, and the mixture was stirred for 5 minutes. N,N-Dimethyl acetamide (3.5 ml) was added to the reaction liquid at the same temperature, and the mixture was stirred for 2 hours. Water and ethyl acetate were added to the reaction liquid and the phases were separated, and the organic layer was dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography on silica gel (hexane-ethyl acetate) to give 1-(5-methyl-2-pyridyl)ethanone (3.43 g, 87percent) as an oily product. 1H-NMR (400 MHz, CDCl3)δ: 2.42 (3H, s), 2.71 (3H, s), 7.62 (1H, dd, J = 1.59, 7.93 Hz), 7.94 (1H, d, J = 7.93 Hz), 8.50 (1H, s).
87%
Stage #1: With n-butyllithium In diethyl ether; hexane at -78℃; for 0.166667 h;
Stage #2: for 2 h;
1)
1-(5-Methyl-2-pyridyl)ethanone
At -78°C, n-butyllithium (1.58M hexane solution, 24 mL) was added dropwise to 2-bromo-5-picoline (5.0 g) in diethyl ether (100 mL) over 5 minutes, followed by stirring for 5 minutes.
Subsequently, N,N-dimethylacetamide (3.5 mL) was added dropwise to the reaction mixture, followed by stirring for 2 hours.
The reaction mixture was partitioned between water and ethyl acetate.
The organic layer was dried over magnesium sulfate anhydrate.
After a filtration step, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane - ethyl acetate), to thereby give 1-(5-methyl-2-pyridyl)ethanone as an oily product (3.43 g, 87percent).
1H-NMR(400MHz,CDCl3)δ:2.42(3H,s), 2.71(3H,s), 7.62(1H,dd,J=1.59,7.93Hz), 7.94(1H,d,J=7.93Hz), 8.54(1H,s).
87%
Stage #1: With n-butyllithium In diethyl ether; hexane at -78℃; for 0.166667 h;
Stage #2: for 2 h;
2) 1-(5-Methyl-2-pyridyl)-1-ethanone n-Butyllithium (a 1.58 M solution in hexane, 24 mL) was added dropwise to a solution of 2-bromo-5-picoline (5.0 g) in diethyl ether (100 mL) over 5 minutes under cooling to -78°C, and then the resultant mixture was stirred for 5 minutes. N, N-dimethylacetamide (3.5 mL) was added dropwise to the reaction solution, and then the mixture was stirred for 2 hours. Water and ethyl acetate were added to the reaction solution, and the mixture was partitioned. The organic layer was dried over anhydrous magnesium sulfate. After separation by filtration, a residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (hexane-ethyl acetate), to obtain 1-(5-methyl-2-pyridyl)-1-ethanone (3.43 g, 87percent) as an oily product. 1H-NMR(400MHz, CDCl3)δ: 2.42(3H, s), 2.71(3H, s), 7.62(1H, dd, J=1.59, 7.93Hz), 7.94(1H, d, J=7.93Hz), 8.54(1H, s).
72%
Stage #1: With n-butyllithium In hexanes; diethyl ether at -78 - -40℃; for 0.25 h;
Stage #2: at -78℃; for 2 h;
Stage #3: With ammonium chloride In hexanes; diethyl ether; water
To a solution of 2-bromo-5-methyl pyridine 23 (1.73 g, 10 mmol) in dry ether (20 ml), cooled to -78 0C, was added n-butyllithium (6.25 ml of 1.6M solution in hexanes, 10 mmol, 1 equiv) dropwise. The reaction mixture was allowed to warm to -40 0C for 15 min, then cooled back to -78 0C again. N,N-dimethylacetamide (1.023 ml, 1 1 mmol, 1.1 equiv) was added dropwise and the mixture was stirred at -78 0C for 2h. Saturated aqueous ammonium chloride (10 ml) was added and the organic layer was separated. The aqueous <n="24"/>layer was extracted with ether (3 x 10 ml) and the combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to give an oily residue that was subjected to flash column chromatography using (5percent methanol in methylene chloride) to give compound 25 (0.977 g, 72percent) as a yellow oil: TLC R/= 0.48 (silica gel, 25percent EtOAc/hexanes); 1H NMR (400 MHz, CDCl3) δ 8.5-8.48 (broad s, IH), 7.94 (d, J= 8.0 Hz, IH), 7.63-7.60 (m, IH), 2.70 (s, 3H), 2.41 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 200.2, 151.7, 149.7, 137.8, 137.4, 121.7, 26.0, 18.9; HRMS calcd for C8H9NO + Na+ 158.0582; found 158.0580 [M + Na+].

Reference: [1] Inorganic Chemistry, 2018,
[2] Patent: EP1698626, 2006, A1, . Location in patent: Page/Page column 48
[3] Patent: EP1762568, 2007, A1, . Location in patent: Page/Page column 30
[4] Patent: EP1785418, 2007, A1, . Location in patent: Page/Page column 38
[5] Chemistry - A European Journal, 2008, vol. 14, # 2, p. 570 - 581
[6] Angewandte Chemie - International Edition, 2016, vol. 55, # 16, p. 4962 - 4966[7] Angew. Chem., 2016, vol. 128, p. 5046 - 5050,5
[8] Patent: WO2008/118327, 2008, A1, . Location in patent: Page/Page column 22-23; Sheet3/13
[9] Angewandte Chemie - International Edition, 2017, vol. 56, # 40, p. 12102 - 12106[10] Angew. Chem., 2017, vol. 129, # 40, p. 12270 - 12274,5
[11] New Journal of Chemistry, 2008, vol. 32, # 6, p. 1048 - 1054
  • 21
  • [ 127-19-5 ]
  • [ 5308-63-4 ]
YieldReaction ConditionsOperation in experiment
72%
Stage #1: With n-butyllithium In hexanes; diethyl ether at -78 - -40℃; for 0.25 h;
Stage #2: at -78℃; for 2 h;
Stage #3: With ammonium chloride In hexanes; diethyl ether; water
[00219] l-(5-methylpyridin-2-yl)-ethanone (51)[00220] To a solution of 2-bromo-5 -methyl pyridine 49 (1.73 g, 10 mmol) in dry ether (20 ml), cooled to -78 0C, was added n-butyllithium (6.25 ml of 1.6M solution in hexanes, 10 mmol, 1 equiv) dropwise. The reaction mixture was allowed to warm to -40 0C for 15 min, then cooled back to -78 0C again. N,N-dimethylacetamide (1.023 ml, 11 mmol, 1.1 equiv) was added dropwise and the mixture was stirred at -78 0C for 2h. Saturated aqueous ammonium chloride (10 ml) was added and the organic layer was separated. The aqueous layer was extracted with ether (3 x 10 ml) and the combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to give an oily residue that was subjected to flash column chromatography using (5percent methanol in methylene chloride) to give compound 51 (0.977 g, 72percent) as a yellow oil: TLC R/= 0.48 (silica gel, 25percent EtOAc / EPO <DP n="40"/>hexanes); 1HNMR (400 MHz5 CDCl3) δ 8.5-8.48 (m, IH), 7.96-7.93 (d, 3J= 8 Hz, IH)5 7.63- 7.60 (m, IH), 2.70 (s, 3H)5 2.414 (s, 3H); 13C NMR (75 MHz5 CDCl3) δ 200.239, 151.741, 149.704, 137.786, 137.442, 121.663, 26.017, 18.969; HRMS calcd for C8H9NO + Na+ 158.0582; found 158.0580 [M + Na+].
Reference: [1] Patent: WO2007/15929, 2007, A2, . Location in patent: Page/Page column 37-38; 7/22
  • 22
  • [ 1603-41-4 ]
  • [ 127-19-5 ]
  • [ 5308-63-4 ]
Reference: [1] Tetrahedron Letters, 1995, vol. 36, # 15, p. 2551 - 2554
  • 23
  • [ 127-19-5 ]
  • [ 1197-55-3 ]
  • [ 18699-02-0 ]
YieldReaction ConditionsOperation in experiment
95.2% at 168℃; for 2 h; Heating mixing p-aminophenylacetic acid, N, N-dimethylacetamide and ammonium chloride, heating to 168 ° C, refluxing for 2 h, and then cooling to room temperature, Add ice water to 4 , insulation crystallization 50min, filtration, washing with ice water filter cake, adjust the temperature to 65 , vacuum drying 4.5h to be acetamidophenylacetic acid, of which p-aminophenylacetic acid, N, N-bis The weight ratio (g / ml) ratio of methylacetamide is 3:15, the weight ratio of p-aminophenylacetic acid and ammonium chloride is 3: 1.5, and the weight ratio of p-aminophenylacetic acid to ice water during crystallization is For 3: 8.
Reference: [1] Patent: CN106278925, 2017, A, . Location in patent: Paragraph 0029-0030
  • 24
  • [ 6727-87-3 ]
  • [ 127-19-5 ]
  • [ 758-96-3 ]
  • [ 1188-14-3 ]
Reference: [1] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1982, vol. 31, # 4, p. 841 - 843[2] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1982, # 4, p. 949 - 951
  • 25
  • [ 127-19-5 ]
  • [ 59983-62-9 ]
  • [ 74-88-4 ]
  • [ 758-96-3 ]
  • [ 1661-08-1 ]
Reference: [1] Journal of Organometallic Chemistry, 1988, vol. 352, p. C51 - C53
  • 26
  • [ 127-19-5 ]
  • [ 74-88-4 ]
  • [ 758-96-3 ]
Reference: [1] Organometallics in Chemical Synthesis, 1971, vol. 1, p. 237 - 247
[2] J. Gen. Chem. USSR (Engl. Transl.), 1983, vol. 53, # 8, p. 1654 - 1658[3] Zhurnal Obshchei Khimii, 1983, vol. 53, # 8, p. 1838 - 1843
[4] Journal of Organometallic Chemistry, 1983, vol. 248, # 1, p. 51 - 60
  • 27
  • [ 127-19-5 ]
  • [ 926-64-7 ]
  • [ 758-96-3 ]
  • [ 67-64-1 ]
Reference: [1] Tetrahedron Letters, 1987, vol. 28, # 36, p. 4177 - 4178
  • 28
  • [ 127-19-5 ]
  • [ 4963-47-7 ]
Reference: [1] Patent: US5097072, 1992, A,
  • 29
  • [ 127-19-5 ]
  • [ 111-27-3 ]
  • [ 1118-92-9 ]
Reference: [1] Journal of the American Chemical Society, 2016, vol. 138, # 34, p. 10786 - 10789
[2] RSC Advances, 2013, vol. 3, # 33, p. 13702 - 13704
[3] Organic and Biomolecular Chemistry, 2016, vol. 14, # 39, p. 9215 - 9220
  • 30
  • [ 111-25-1 ]
  • [ 127-19-5 ]
  • [ 1118-92-9 ]
Reference: [1] Comptes Rendus des Seances de l'Academie des Sciences, Serie C: Sciences Chimiques, 1974, vol. 278, p. 1105 - 1108
[2] Canadian Journal of Chemistry, 1976, vol. 54, p. 1098 - 1104
[3] Heterocycles, 1990, vol. 31, # 7, p. 1205 - 1211
  • 31
  • [ 127-19-5 ]
  • [ 2044-64-6 ]
Reference: [1] Tetrahedron, 1982, vol. 38, # 4, p. 557 - 561
[2] Chemische Berichte, 1959, vol. 92, p. 1456,1458
[3] Chemische Berichte, 1961, vol. 94, p. 3119 - 3128
[4] Chemistry Letters, 1991, p. 1965 - 1968
  • 32
  • [ 127-19-5 ]
  • [ 92444-87-6 ]
  • [ 2044-64-6 ]
Reference: [1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1984, # 6, p. 1173 - 1182
  • 33
  • [ 127-19-5 ]
  • [ 64670-05-9 ]
  • [ 29736-80-9 ]
Reference: [1] Tetrahedron, 1988, vol. 44, # 15, p. 4767 - 4776
[2] Chemistry Letters, 1985, p. 1145 - 1148
[3] Chemistry Letters, 1985, p. 1145 - 1148
  • 34
  • [ 127-19-5 ]
  • [ 217813-03-1 ]
  • [ 15799-79-8 ]
  • [ 703-23-1 ]
  • [ 1220955-97-4 ]
YieldReaction ConditionsOperation in experiment
34%
Stage #1: at 20℃; for 3 h; Inert atmosphere
Stage #2: at 20℃;
To a solution of TBAF (157 mg, 0.60 mmol) in DMA (1.2 mL) was added a solution of 3-methoxy-2-(trimethylsilyl)phenyl triflate 1 (53 μL, 0.20 mmol) in DMA (0.8 mL) under argon atmosphere at room temperature. After being stirred at the same temperature for 3 h, H2O (0.1 mL) was added to the reaction mixture. The reaction mixture was concentrated under reduced pressure. Purification of the residue by flash silica gel column chromatography (AcOEt/hexane=1/20 to 1/8 with 2percent CH2Cl2) afforded the products 10 (11.3 mg, 34percent), 11 (3.8 mg, 10percent), and 12 (1.3 mg, 5percent).3.6.1. 2-Hydroxy-6-methoxyacetophenone (10)refPreviewPlaceHolder28CommentCommentColorless crystals. Mp 57-57.5 °C (AcOEt/hexane). IR (KBr) 3110, 3009, 2947, 1623, 1594, 1459 cm-1. 1H NMR (CDCl3) δ 13.23 (1H, s), 7.33 (1H, t, J=8.0 Hz), 6.56 (1H, dd, J=8.0, 1.0 Hz), 6.39 (1H, dd, J=8.0, 1.0 Hz), 3.90 (3H, s), 2.67 (3H, s). 13C NMR (CDCl3) δ 205.1, 164.6, 161.5, 136.0, 111.3, 110.7, 101.1, 55.6, 33.7. MS (EI+) m/z 83 (100), 166 (M+, 3). HRMS (EI+) calcd for C9H10O3 (M+) 166.0624, found 166.0646.3.6.2. 2-(N,N-Dimethyl)amino-6-methoxyacetophenone (11)CommentCommentColorless oil. IR (CHCl3) 2942, 1702, 1577, 1468 cm-1. 1H NMR (CDCl3) δ 7.23 (1H, br t, J=8.0 Hz), 6.67 (1H, br d, J=8.0 Hz), 6.56 (1H, br d, J=8.0 Hz), 3.78 (3H, s), 2.72 (6H, s), 2.50 (3H, s). 13C NMR (CDCl3) δ 205.2, 156.2, 151.8, 130.2, 125.3, 111.0, 104.7, 55.8, 44.8, 31.8. MS (EI+) m/z 83 (100), 193 (M+, 0.4). HRMS (EI+) calcd for C11H15NO2 (M+) 193.1097, found 193.1121.3.6.3. 3-Methoxy-N,N-dimethylaniline (12)refPreviewPlaceHolder29CommentCommentColorless oil. IR (KBr) 2955, 1610, 1493, 1465 cm-1. 1H NMR (CDCl3) δ 7.15 (1H, t, J=8.0 Hz), 6.36 (1H, dd, J=8.0, 2.5 Hz), 6.31-6.27 (2H, m), 3.80 (3H, s), 2.94 (6H, s). 13C NMR (CDCl3) δ 160.6, 151.9, 129.7, 105.7, 101.3, 99.1, 55.1, 40.6. MS (EI+) m/z 83 (100), 151 (M+, 0.4). HRMS (EI+) calcd for C9H14NO (M+H+) 152.1070, found 152.1055.
Reference: [1] Tetrahedron, 2012, vol. 68, # 1, p. 179 - 189
[2] Tetrahedron, 2012, vol. 68, # 1, p. 179 - 189
  • 35
  • [ 127-19-5 ]
  • [ 217813-03-1 ]
  • [ 703-23-1 ]
  • [ 1220955-97-4 ]
Reference: [1] Organic Letters, 2010, vol. 12, # 9, p. 1956 - 1959
  • 36
  • [ 127-19-5 ]
  • [ 14401-73-1 ]
YieldReaction ConditionsOperation in experiment
41%
Stage #1: With n-butyllithium In diethyl ether at -78℃; for 3 h;
Stage #2: at -78 - 20℃; for 20 h;
Synthetic Example 10
Synthesis of 1-(3,5-dibromophenyl)-1-phenyl-2-methylenecyclopropane
A round-bottomed flask was charged with 1,3,5-tribromobenzene (6.3 g, 20 mmol) and dry ether (150 mL) under a nitrogen atmosphere.
A solution of n-butyllithium (12.5 mL, 20 mmol) was added thereto while cooling at -78° C., and stirring at -78° C. was carried out for 2 hours.
A solution of N,N-dimethylacetamide (1.92 g, 22 mmol) in dry ether (15 mL) was further added dropwise thereto.
The temperature was gradually returned from -78° C. to room temperature, stirring was carried out for 20 hours, extraction with ether was then carried out, and the solvent was removed by distillation.
Purification was carried out by column chromatography and recrystallization to give 3,5-dibromoacetophenone.
Yield 41percent.
Reference: [1] Patent: US2007/138945, 2007, A1, . Location in patent: Page/Page column 11
  • 37
  • [ 127-19-5 ]
  • [ 626-39-1 ]
  • [ 14401-73-1 ]
Reference: [1] Journal of Organic Chemistry, 2001, vol. 66, # 6, p. 2104 - 2117
[2] Journal of Organic Chemistry, 1998, vol. 63, # 21, p. 7399 - 7407
[3] Molecular Crystals and Liquid Crystals, 2007, vol. 462, # 1, p. 159 - 167
[4] Journal of the American Chemical Society, 1992, vol. 114, # 3, p. 1018 - 1025
[5] Angewandte Chemie - International Edition, 2004, vol. 43, # 44, p. 5936 - 5940
  • 38
  • [ 127-19-5 ]
  • [ 591-20-8 ]
  • [ 121-71-1 ]
Reference: [1] Tetrahedron Letters, 1993, vol. 34, # 13, p. 2043 - 2046
  • 39
  • [ 127-19-5 ]
  • [ 765-70-8 ]
Reference: [1] Patent: US4007216, 1977, A,
  • 40
  • [ 109-69-3 ]
  • [ 127-19-5 ]
  • [ 123-30-8 ]
  • [ 4344-55-2 ]
Reference: [1] Patent: US4124640, 1978, A,
  • 41
  • [ 127-19-5 ]
  • [ 133622-65-8 ]
  • [ 367-34-0 ]
Reference: [1] Patent: EP415585, 1991, A1,
  • 42
  • [ 127-19-5 ]
  • [ 18959-31-4 ]
  • [ 455-86-7 ]
Reference: [1] Patent: US4937377, 1990, A,
[2] Patent: US4937377, 1990, A,
  • 43
  • [ 127-19-5 ]
  • [ 615-36-1 ]
  • [ 614-76-6 ]
YieldReaction ConditionsOperation in experiment
80% at 150℃; for 6 h; Sealed tube General procedure: To a mixture of aromatic or aliphatic or heterocyclic amine (3.0 mmol, 1.0 equiv.), Imidazolium chloride (1.0 mmol, 0.3 equiv.), N,N-Dimethyl acetamide (2.0 mL) was added. The mixture was refluxed at 150 °C and the progress of the reaction was monitored by TLC visualized with UV short wavelength followed by iodine stain. After completion, the mixture was diluted with cold water(10 mL) then extracted with EtOAc (10 mL). The EtOAc layer was washed with 1 M hydrochloric acid (3.0 15 mL). Adsorption of pigment with activated carbon, filtration of filtrate. The filtrate was dried over anhydrous Na2SO4 and concentrated under vacuum to obtain crude N-acetamide amine, the N-acetamide amine product was isolated by column chromatography eluting with petroleum ether:ethyl acetate (10:1) mixtures.
Reference: [1] Molecules, 2018, vol. 23, # 9,
  • 44
  • [ 591-50-4 ]
  • [ 127-19-5 ]
  • [ 95-68-1 ]
  • [ 25078-04-0 ]
  • [ 2050-43-3 ]
Reference: [1] ChemCatChem, 2018, vol. 10, # 17, p. 3907 - 3913
  • 45
  • [ 616-47-7 ]
  • [ 127-19-5 ]
  • [ 85692-37-1 ]
Reference: [1] Organic Process Research and Development, 2014, vol. 18, # 10, p. 1211 - 1220
  • 46
  • [ 19798-81-3 ]
  • [ 127-19-5 ]
  • [ 25218-99-9 ]
YieldReaction ConditionsOperation in experiment
89% at 150℃; for 3 h; Sealed tube General procedure: To a mixture of aromatic or aliphatic or heterocyclic amine (3.0 mmol, 1.0 equiv.), Imidazolium chloride (1.0 mmol, 0.3 equiv.), N,N-Dimethyl acetamide (2.0 mL) was added. The mixture was refluxed at 150 °C and the progress of the reaction was monitored by TLC visualized with UV short wavelength followed by iodine stain. After completion, the mixture was diluted with cold water(10 mL) then extracted with EtOAc (10 mL). The EtOAc layer was washed with 1 M hydrochloric acid (3.0 15 mL). Adsorption of pigment with activated carbon, filtration of filtrate. The filtrate was dried over anhydrous Na2SO4 and concentrated under vacuum to obtain crude N-acetamide amine, the N-acetamide amine product was isolated by column chromatography eluting with petroleum ether:ethyl acetate (10:1) mixtures.
Reference: [1] Molecules, 2018, vol. 23, # 9,
  • 47
  • [ 624-28-2 ]
  • [ 127-19-5 ]
  • [ 139042-59-4 ]
YieldReaction ConditionsOperation in experiment
47%
Stage #1: With n-butyllithium In diethyl ether; hexane at -78℃; for 1 h; Inert atmosphere
Stage #2: at -78℃; for 4 h; Inert atmosphere
Step 1:
Synthesis of 1-(6-bromopyridin-3-yl)ethanone
To a stirred solution of 2,5-dibromopyridine (1.0 g, 4.219 mmol) in diethyl ether (10 mL) at -78° C. was added n-Butyl lithium (2.0 mL, 5.0 mmol, 2.5M in hexane) under nitrogen and stirred for 1 h at the same temperature.
Dimethyl acetamide (0.58 g, 6.3 mmol) was then added drop wise to the reaction mixture, stirred for 4 h at -78° C.
Progress of reaction was monitored by TLC.
After completion reaction mass was quenched with ice cold water and partitioned between saturated NH4Cl solution and EtOAc.
The organic layer was washed with brine, dried over sodium sulphate and concentrated under reduced pressure to give 1-(6-bromopyridin-3-yl) ethanone (0.4 g, 47percent) as yellow solid
MS: 200.1 [M++1]
Reference: [1] Molecules, 2008, vol. 13, # 4, p. 818 - 830
[2] Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 24, p. 6763 - 6770
[3] Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 11, p. 3860 - 3874
[4] Patent: US2017/291894, 2017, A1, . Location in patent: Paragraph 0428
[5] Chemische Berichte, 1992, vol. 125, # 5, p. 1169 - 1190
  • 48
  • [ 42142-52-9 ]
  • [ 127-19-5 ]
  • [ 98-56-6 ]
  • [ 202122-33-6 ]
  • [ 56296-78-7 ]
Reference: [1] Organic Process Research and Development, 2014, vol. 18, # 7, p. 875 - 885
  • 49
  • [ 3189-13-7 ]
  • [ 127-19-5 ]
  • [ 99532-52-2 ]
Reference: [1] Archiv der Pharmazie, 2014, vol. 347, # 8, p. 533 - 539
[2] European Journal of Medicinal Chemistry, 2017, vol. 125, p. 591 - 598
  • 50
  • [ 127-19-5 ]
  • [ 17422-32-1 ]
  • [ 51843-24-4 ]
Reference: [1] Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 7, p. 2269 - 2279
  • 51
  • [ 624-28-2 ]
  • [ 127-19-5 ]
  • [ 214701-49-2 ]
YieldReaction ConditionsOperation in experiment
100% With n-butyllithium In hexane; toluene at -40 - 20℃; for 2 h; Inert atmosphere 2,5-dibromo-pyridine (I-1-1) 8g the (33.7mmol) and toluene 337mL was stirred at -40 under a nitrogen atmosphere. After stirring for 40 minutes was added n- butyl lithium 1.6M in hexane 21.4mL a (1.02eq) in which, in addition N, N-dimethylacetamide (DMAc) 9.38mL (3.0eq), stirred It was slowly heated to 20 while. Thereafter, saturated aqueous ammonium chloride solution was added to quench the reaction, and extraction and liquid separation. The extract was purified by silica gel column chromatography,2-acetyl-5-bromopyridine to give (compound the I-1-2) of a white solid 6.74 g (100percent yield).
65%
Stage #1: With n-butyllithium In hexane; toluene at -50℃; for 0.75 h;
Stage #2: at -50 - 20℃; for 1 h;
To a solution of 2,5-dibromopyridine (5 g, 22.026 mmol) in anhydrous toluene (200 mL) at -50 °C was added n-butyllithium (13.75 mL, 22.026 mmol) (1.6M in hexane) dropwise. The resulted mixture was stirred at -50 °C temperature for 45 mi N,Ndimethylacetamide (3.61 mL, 37.44 mmol) was added dropwise at the same temperatureand then allowed to reach room temperature slowly. The reaction mixture was stirred at room temperature for 1 h and quenched with saturated ammonium chloride solution, then extracted with EtOAc. The organic layer was dried over sodium sulfate, concentrated and purified by column chromatography (60-120 silica gel, 1percent EtOAc/hexane) to provide the product of Step 1 (2.9 g, 65percent yield) as a white solid. LCMS retention time: 1.46 mm(Method 7).
Reference: [1] Patent: JP2016/56276, 2016, A, . Location in patent: Paragraph 0111; 0112
[2] Tetrahedron, 2008, vol. 64, # 17, p. 3794 - 3801
[3] Dalton Transactions, 2011, vol. 40, # 29, p. 7534 - 7540
[4] Journal of the American Chemical Society, 2016, vol. 138, # 38, p. 12643 - 12647
[5] Patent: WO2015/27021, 2015, A1, . Location in patent: Page/Page column 78
[6] Patent: WO2012/21467, 2012, A1, . Location in patent: Page/Page column 32
  • 52
  • [ 127-19-5 ]
  • [ 79099-07-3 ]
  • [ 157327-41-8 ]
YieldReaction ConditionsOperation in experiment
94.4% at 95℃; for 1.5 h; S1.A 250 ml flask was charged with N-tert-butoxycarbonyl-4-piperidone (1) (12 g, 60 mmol) and 150 ml of DMF-DMA,The reaction at 95 1.5h,TLC showed the reaction was complete,Concentration gave 3 - ((N, N-dimethylamino) -methylene) -N-tert- butoxycarbonyl-4piperidone (2) (white solid, 14.4 g)Yield 94.4percent.
Reference: [1] Patent: CN106397433, 2017, A, . Location in patent: Paragraph 0025; 0030
  • 53
  • [ 40473-01-6 ]
  • [ 127-19-5 ]
  • [ 94952-46-2 ]
YieldReaction ConditionsOperation in experiment
85%
Stage #1: With sec.-butyllithium In diethyl ether; hexane at -60℃; for 2 h;
Stage #2: for 3 h;
Stage #3: With hydrogenchloride; water In diethyl ether; hexane
2-Bromo-5-chloropyridine (5.8g, 30mmol) was added to dry diethyl ether (100ml). The mixture was cooled to-60°C and a solution of sec-BuLi (1.4M solution in hexanes, 22mL) was added dropwise and the mixture was stirred for 2hrs. A solution of N, N- dimethylacetamide (3. 1ml, 33mmol) in diethyl ether (20ml) was added slowly dropwise and the solution left to stir for 3hrs. The reaction was brought to room temperature, hydrolysed with 2N HC1 and extracted with DCM. The organic phase was washed with water, dried over MgS04 and evaporated to give 1- (5-Chloro-pyridin-2-yl)-ethanone (4. 0g, 85percent).
59%
Stage #1: With n-butyllithium In diethyl ether; hexane at -78℃;
Stage #2: for 0.5 h;
2) 1-(5-chloro-2-pyridyl)ethanone; A 1.56M solution of n-butyllithium in hexane (27 ml) was added dropwise to a solution of the 2-bromo-5-chloropyridine (6.8 g) in diethylether (45 ml) at-78°C, and thereafter, N,N-dimethyl acetamide (5 ml) was added dropwise to the solution. The mixture was stirred for 30 minutes. To the reaction liquid was added saturated aqueous ammonium chloride and ethyl acetate, and the phases were separated. The organic layer was dried over anhydrous sodium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography on silica gel (hexane-ethyl acetate) to give 1-(5-chloro-2-pyridyl)ethanone (3.26 g, 59percent) as a solid. 1H-NMR (400 MHz, CDCl3)δ: 2.70 (3H, s), 7.80 (1H, dd, J = 8.42, 2.32 Hz), 8.00 (1H, d, J = 8.42 Hz), 8.62 (1H, d, J = 2.32 Hz).
59% With n-butyllithium In diethyl ether; hexane at -78℃; for 0.5 h; 2)
1-(5-Chloro-2-pyridyl)ethanone
At -78°C, n-butyllithium (1.56M hexane solution, 27 mL) was added dropwise to 2-bromo-5-chloropyridine (6.8 g) in diethyl ether (45 mL), and then N,N-dimethylacetamide (5 mL) was added dropwise to the resultant mixture, followed by stirring for 30 minutes.
Subsequently, a saturated aqueous solution of ammonium chloride was added to the reaction mixture.
Ethyl acetate was added for partitioning the resultant mixture.
The organic layer was dried over sodium sulfate anhydrate.
After a filtration step, the solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (hexane - ethyl acetate), to thereby give 1-(5-chloro-2-pyridyl)ethanone as a solid product (3.26 g, 59percent).
1H-NMR(400MHz,CDCl3)δ:2.70(3H,s), 7.80(1H,dd,J=8.42,2.32Hz), 8.00(1H,d,J=8.42Hz), 8.62(1H,d,J=2.32Hz).
Reference: [1] Patent: WO2005/92304, 2005, A2, . Location in patent: Page/Page column 43
[2] Patent: EP1698626, 2006, A1, . Location in patent: Page/Page column 41
[3] Patent: EP1762568, 2007, A1, . Location in patent: Page/Page column 25
[4] Patent: US2009/253708, 2009, A1, . Location in patent: Page/Page column 12
  • 54
  • [ 127-19-5 ]
  • [ 436799-32-5 ]
  • [ 358780-14-0 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 17, p. 4999 - 5003
  • 55
  • [ 127-19-5 ]
  • [ 586-89-0 ]
  • [ 1008119-09-2 ]
Reference: [1] Journal of Chemical Research, 2013, vol. 37, # 3, p. 155 - 159
  • 56
  • [ 127-19-5 ]
  • [ 1016228-01-5 ]
YieldReaction ConditionsOperation in experiment
34%
Stage #1: With n-butyllithium In diethyl ether; hexane at -66 - -65℃; for 1.5 h;
Stage #2: at -65℃; for 2.16667 h;
Stage #3: With hydrogenchloride In diethyl ether; hexane; water at -65 - 20℃;
a) l-(6-Bromo-3-fluoro-pyridin-2-yl)ethanone2-Bromo-5-fluoro-pyridine (11 g, 62.5 mmol) was dissolved in diethyl ether at room temperature under a nitrogen atmosphere.The reaction mixture was cooled until the <n="34"/>internal temperature was -66 0C . Butyl lithium (2.5 M in hexanes, 26 mL, 65 mmol) was added dropwise over 0.5 h. The resulting reaction mixture was left at -65 0C for 1 h. NJf- Dimethylacetamide (6.5 mL, 70 mmol) was added over 10 min. and the reaction mixture was stirred at -65 0C for 2 h. IM hydrochloric acid aq. (50 mL) was added and the mixture was warmed to room temperature. The pH was adjusted to 7 with additional hydrochloric acid. The aqueous phase was extracted with diethyl ether three times. The combined organic phases were washed with Brine, dried over sodium sulphate, and concentrated in vacuo. Purification by flash column chromatography (eluent heptane:diethyl ether gradient) yielded 4.6 g (34percent yield) of the title compound. 1H NMR (300 MHz, DMSO-J6): 8.0-7.8 (m, 2H); 2.57 (s, 3H); MS (ESI) m/z 218 and 220 [MH]+.
34%
Stage #1: With n-butyllithium In diethyl ether; hexane at -66 - -65℃; for 1.5 h;
Stage #2: at -65℃; for 2.16667 h;
Stage #3: With hydrogenchloride In diethyl ether; hexane; water at -65 - 20℃;
a) l-(6-Bromo-3-fluoro-pyridin-2-yl)ethanone <n="41"/>2-Bromo-5-fluoro-pyridine (11 g, 62.5 mmol) was dissolved in diethyl ether at room temperature under a nitrogen atmosphere.The reaction mixture was cooled until the internal temperature was -66 0C . Butyl lithium (2.5 M in hexanes, 26 mL, 65 mmol) was added dropwise over 0.5 h. The resulting reaction mixture was left at -65 °C for 1 h. NJV- Dimethylacetamide (6.5 mL, 70 mmol) was added over 10 min. and the reaction mixture was stirred at -65 0C for 2 h. IM hydrochloric acid aq. (50 mL) was added and the mixture was warmed to room temperature. The pH was adjusted to 7 with additional hydrochloric acid. The aqueous phase was extracted with diethyl ether three times. The combined organic phases were washed with Brine, dried over sodium sulphate, and concentrated in vacuo. Purification by flash column chromatography (eluent heptane: diethyl ether gradient) yielded 4.6 g (34percent yield) of the title compound.H NMR (300 MHz, DMSO-J6): 8.0-7.8 (m, 2H); 2.57 (s, 3H); MS (ESI) m/z 218 and 220+[M+l] " .
Reference: [1] Patent: WO2008/39139, 2008, A1, . Location in patent: Page/Page column 32; 33
[2] Patent: WO2008/39138, 2008, A1, . Location in patent: Page/Page column 39; 40
  • 57
  • [ 84249-14-9 ]
  • [ 127-19-5 ]
  • [ 1026796-81-5 ]
Reference: [1] RSC Advances, 2015, vol. 5, # 14, p. 10567 - 10574
Same Skeleton Products
Historical Records

Related Functional Groups of
[ 127-19-5 ]

Aliphatic Chain Hydrocarbons

Chemical Structure| 38806-26-7

[ 38806-26-7 ]

N-ethyl-N-methylacetamide

Similarity: 0.89

Chemical Structure| 685-91-6

[ 685-91-6 ]

N,N-Diethylacetamide

Similarity: 0.89

Chemical Structure| 758-96-3

[ 758-96-3 ]

N,N-Dimethylpropionamide

Similarity: 0.77

Chemical Structure| 14658-93-6

[ 14658-93-6 ]

2-Hydroxy-N,N-dimethylacetamide

Similarity: 0.74

Chemical Structure| 5468-77-9

[ 5468-77-9 ]

2-Bromo-N,N-dimethylacetamide

Similarity: 0.71

Amides

Chemical Structure| 38806-26-7

[ 38806-26-7 ]

N-ethyl-N-methylacetamide

Similarity: 0.89

Chemical Structure| 685-91-6

[ 685-91-6 ]

N,N-Diethylacetamide

Similarity: 0.89

Chemical Structure| 18940-57-3

[ 18940-57-3 ]

1,1'-(Piperazine-1,4-diyl)diethanone

Similarity: 0.77

Chemical Structure| 13889-98-0

[ 13889-98-0 ]

1-Acetylpiperazine

Similarity: 0.77

Chemical Structure| 758-96-3

[ 758-96-3 ]

N,N-Dimethylpropionamide

Similarity: 0.77

Amines

Chemical Structure| 38806-26-7

[ 38806-26-7 ]

N-ethyl-N-methylacetamide

Similarity: 0.89

Chemical Structure| 685-91-6

[ 685-91-6 ]

N,N-Diethylacetamide

Similarity: 0.89

Chemical Structure| 758-96-3

[ 758-96-3 ]

N,N-Dimethylpropionamide

Similarity: 0.77

Chemical Structure| 14658-93-6

[ 14658-93-6 ]

2-Hydroxy-N,N-dimethylacetamide

Similarity: 0.74

Chemical Structure| 5468-77-9

[ 5468-77-9 ]

2-Bromo-N,N-dimethylacetamide

Similarity: 0.71