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Chemical Structure| 20970-75-6
Chemical Structure| 20970-75-6
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Product Details of [ 20970-75-6 ]

CAS No. :20970-75-6 MDL No. :MFCD00190585
Formula : C7H6N2 Boiling Point : -
Linear Structure Formula :- InChI Key :WBXZCDIZXWDPBL-UHFFFAOYSA-N
M.W : 118.14 Pubchem ID :819928
Synonyms :

Calculated chemistry of [ 20970-75-6 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 9
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.14
Num. rotatable bonds : 0
Num. H-bond acceptors : 2.0
Num. H-bond donors : 0.0
Molar Refractivity : 33.92
TPSA : 36.68 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.12 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.49
Log Po/w (XLOGP3) : 1.27
Log Po/w (WLOGP) : 1.26
Log Po/w (MLOGP) : 0.13
Log Po/w (SILICOS-IT) : 1.78
Consensus Log Po/w : 1.19

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -1.87
Solubility : 1.61 mg/ml ; 0.0136 mol/l
Class : Very soluble
Log S (Ali) : -1.64
Solubility : 2.71 mg/ml ; 0.0229 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -2.45
Solubility : 0.423 mg/ml ; 0.00358 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.59

Safety of [ 20970-75-6 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 20970-75-6 ]

* 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 [ 20970-75-6 ]
  • Downstream synthetic route of [ 20970-75-6 ]

[ 20970-75-6 ] Synthesis Path-Upstream   1~46

  • 1
  • [ 1003-73-2 ]
  • [ 20970-75-6 ]
YieldReaction ConditionsOperation in experiment
88.6%
Stage #1: With N,N-Dimethylcarbamoyl chloride In 1,4-dioxane at 45℃; for 2 h;
Stage #2: at -10 - 6℃; for 2.5 h;
To the drying reactor was added 3-methylpyridine-N-oxide (2.94 g, 27 mmol) Dioxane 50ml, Stirred at room temperature for 5 minutes, Then, dimethylcarbamoyl chloride (7.82 g, 72 mmol) was slowly added thereto, Continue stirring for 5 minutes. Then heated to 45 ° C, Insulation reaction for 2 hours. The reaction solution was cooled to room temperature, Into the low temperature tank, -10 to 6 ° C under the conditions of adding 26.5percent (w / w) Of potassium cyanide (16.55 g, 67 mmol) in water, Insulation reaction for 2.5 hours. Add 6.2percent (w / w) Of aqueous NaOH solution 22ml, Stir for 10 min. Dichloromethane extraction, The solvent was distilled off under reduced pressure, Acetonitrile-water (1:30) to give 2.82 g of white crystals, Yield 88.6percent
Reference: [1] Patent: CN104725304, 2017, B, . Location in patent: Paragraph 0094; 0097; 0100; 0103; 0106; 0107-0109
  • 2
  • [ 1003-73-2 ]
  • [ 20970-75-6 ]
YieldReaction ConditionsOperation in experiment
18.6% With dimethyl sulfate In water II-1-1:
Synthesis of 2-cyano-3-methylpyridine
After a mixture of 10.9 g (0.1 mol) of 3-methylpyridine N-oxide and 12.6 g (0.1 mol) of dimethyl sulfate was stirred under heating at 70° to 75° C. for 2 hours, to the resultant solution was dropwise added a solution of 13.0 g (0.2 mol) of potassium cyanide dissolved in 40 ml of water at 10° C. or lower, while stirring.
After the mixture was stirred at the same temperature for one hour, and further, at room temperature for one hour, 150 ml of water was added and the mixture was extracted with dichloromethane.
After drying over anhydrous sodium sulfate, the extract was concentrated and separated by silica gel column chromatography (with ethyl:hexane=2:8 to 3:7 for the first time, 2:8 for the second time), and recrystallized from hexane to obtain 2.20 g of a colorless solid (yield 18.6percent).
m.p.: 82.5°-83.5° C.
IR (KBr): 2210, 1560 cm-1.
Reference: [1] Patent: US5219847, 1993, A,
[2] Chemical and Pharmaceutical Bulletin, 1959, vol. 7, p. 925,928
  • 3
  • [ 4390-78-7 ]
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Reference: [1] Patent: EP1559711, 2005, A1, . Location in patent: Page/Page column 23
  • 4
  • [ 773837-37-9 ]
  • [ 1104027-41-9 ]
  • [ 7584-05-6 ]
  • [ 20970-75-6 ]
Reference: [1] Patent: WO2009/11904, 2009, A1, . Location in patent: Page/Page column 56-57
  • 5
  • [ 1003-73-2 ]
  • [ 7677-24-9 ]
  • [ 1620-77-5 ]
  • [ 20970-75-6 ]
Reference: [1] Journal of Organic Chemistry, 1983, vol. 48, # 8, p. 1375 - 1377
[2] Chemical and Pharmaceutical Bulletin, 1985, vol. 33, # 2, p. 565 - 571
[3] Journal of Heterocyclic Chemistry, 1994, vol. 31, # 5, p. 1289 - 1292
  • 6
  • [ 1003-73-2 ]
  • [ 143-33-9 ]
  • [ 1620-77-5 ]
  • [ 20970-75-6 ]
Reference: [1] Synthesis, 1983, # 4, p. 316 - 319
  • 7
  • [ 108-99-6 ]
  • [ 151-50-8 ]
  • [ 20970-75-6 ]
Reference: [1] Synthesis, 2005, # 6, p. 993 - 997
  • 8
  • [ 108-99-6 ]
  • [ 7677-24-9 ]
  • [ 7584-05-6 ]
  • [ 20970-75-6 ]
Reference: [1] Chemistry - A European Journal, 2017, vol. 23, # 59, p. 14733 - 14737
  • 9
  • [ 1603-40-3 ]
  • [ 20970-75-6 ]
Reference: [1] Journal of the American Chemical Society, 1934, vol. 56, p. 231
[2] Journal of the American Chemical Society, 1952, vol. 74, p. 5967,5969
[3] Journal of Organometallic Chemistry, 1997, vol. 529, # 1-2, p. 135 - 142
[4] Organic Magnetic Resonance, 1982, vol. 20, # 4, p. 242 - 248
  • 10
  • [ 68357-21-1 ]
  • [ 20970-75-6 ]
Reference: [1] Heterocycles, 1980, vol. 14, # 10, p. 1581 - 1602
  • 11
  • [ 4931-46-8 ]
  • [ 20970-75-6 ]
Reference: [1] Journal of Organometallic Chemistry, 1997, vol. 529, # 1-2, p. 135 - 142
  • 12
  • [ 1003-73-2 ]
  • [ 143-33-9 ]
  • [ 20970-75-6 ]
Reference: [1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1984, # 7, p. 1501 - 1505
  • 13
  • [ 583-61-9 ]
  • [ 20970-75-6 ]
Reference: [1] Organic Preparations and Procedures International, 1999, vol. 31, # 1, p. 120 - 123
[2] Organic Preparations and Procedures International, 1999, vol. 31, # 1, p. 120 - 123
[3] Chemical and Pharmaceutical Bulletin, 1985, vol. 33, # 2, p. 565 - 571
  • 14
  • [ 773837-37-9 ]
  • [ 20970-75-6 ]
Reference: [1] Journal of the American Chemical Society, 2017, vol. 139, # 28, p. 9499 - 9502
  • 15
  • [ 1003-73-2 ]
  • [ 7677-24-9 ]
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Reference: [1] Journal of Organic Chemistry, 1990, vol. 55, # 2, p. 738 - 741
  • 16
  • [ 101870-40-0 ]
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Reference: [1] Chemical and Pharmaceutical Bulletin, 1985, vol. 33, # 2, p. 565 - 571
  • 17
  • [ 55589-47-4 ]
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Reference: [1] Organic Preparations and Procedures International, 1999, vol. 31, # 1, p. 120 - 123
  • 18
  • [ 18368-76-8 ]
  • [ 20970-75-6 ]
Reference: [1] Pharmaceutical Bulletin, 1957, vol. 5, p. 13
  • 19
  • [ 151-50-8 ]
  • [ 58202-10-1 ]
  • [ 1620-77-5 ]
  • [ 20970-75-6 ]
Reference: [1] Heterocycles, 1984, vol. 22, # 5, p. 1121 - 1124
[2] Heterocycles, 1984, vol. 22, # 5, p. 1121 - 1124
  • 20
  • [ 7677-24-9 ]
  • [ 58202-10-1 ]
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Reference: [1] Heterocycles, 1984, vol. 22, # 5, p. 1121 - 1124
  • 21
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  • [ 87117-12-2 ]
  • [ 1620-77-5 ]
  • [ 7584-05-6 ]
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Reference: [1] Heterocycles, 1984, vol. 22, # 5, p. 1121 - 1124
  • 22
  • [ 101870-40-0 ]
  • [ 20970-75-6 ]
Reference: [1] Organic Preparations and Procedures International, 1999, vol. 31, # 1, p. 120 - 123
  • 23
  • [ 504-60-9 ]
  • [ 20970-75-6 ]
Reference: [1] Heterocycles, 1980, vol. 14, # 10, p. 1581 - 1602
  • 24
  • [ 151-50-8 ]
  • [ 86488-30-4 ]
  • [ 7584-05-6 ]
  • [ 20970-75-6 ]
Reference: [1] Chemical and Pharmaceutical Bulletin, 1959, vol. 7, p. 925,928
  • 25
  • [ 1003-73-2 ]
  • [ 77-78-1 ]
  • [ 1620-77-5 ]
  • [ 7584-05-6 ]
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Reference: [1] Journal of the American Chemical Society, 1959, vol. 81, p. 4004,4005
  • 26
  • [ 1003-73-2 ]
  • [ 74-88-4 ]
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Reference: [1] Chemical and Pharmaceutical Bulletin, 1959, vol. 7, p. 925,928
  • 27
  • [ 20970-75-6 ]
  • [ 4021-07-2 ]
YieldReaction ConditionsOperation in experiment
54% With sodium carbonate; sodium sulfite In sulfuric acid; water II-1-2:
Synthesis of 3-methylpicolinic acid
A solution of 2.00 g (19 mmol) of 2-cyano-3-methylpyridine dissolved in 90percent sulfuric acid was stirred under heating at 120° C. for 2 hours and then cooled to 20° C.
At a temperature of 20° to 25° C., a solution of 4.00 g of sodium sulfite in 8 ml of water was dropwise added, and the mixture was heated at the same temperature for 1.5 hours and further, at 75° to 85° C. for 1.5 hours, cooled, then adjusted to a pH of about 3 with an addition of sodium carbonate and extracted with chloroform.
After drying over anhydrous sodium sulfate, the extract was concentrated under a reduced pressure to obtain 1.38 g of a solid.
The solid was recrystallized from an ethyl acetate-hexane mixture (yield 54.0percent).
m.p.: 115.5°-116.5° C.
IR (KBr): 3350, 1650, 1590 cm-1.
13.8 g for 8 h; Reflux A mixture of 2-cyano-3-methylpyridine (20.0 g, 169 mmol) and conc. HCl (50 mL) in water (50 mL) was heated under reflux for 8 h. The reaction was evaporated under reduced pressure, the residue azeotroped with water, then triturated with acetone. The resulting pink solid was recrystallised from acetonitrile/water (50:50 by volume) to give an off-white solid (13.8 g).
Reference: [1] Tetrahedron, 2013, vol. 69, # 33, p. 6799 - 6803
[2] Patent: US5219847, 1993, A,
[3] Journal of the American Chemical Society, 1952, vol. 74, p. 5967,5969
[4] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1984, # 7, p. 1501 - 1505
[5] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 1, p. 498 - 509
  • 28
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  • [ 59718-84-2 ]
Reference: [1] Tetrahedron, 2013, vol. 69, # 33, p. 6799 - 6803
  • 29
  • [ 20970-75-6 ]
  • [ 65169-63-3 ]
YieldReaction ConditionsOperation in experiment
40% With tetrabutylammonium nitrate; trifluoroacetic anhydride In tert-butyl methyl ether at 4 - 20℃; for 60 h; A mixture of 3-methylpyridine-2-carbonitrile (128 g, 1.08 mol) and tetrabutylammonium nitrate (363 g, 1 .19 mol) in fe/f-butyl methyl ether (1 .3 L) was cooled to 4 °C. Trifluoroacetic anhydride (171 ml_, 1 .21 mol) was added, and the reaction mixture was allowed to stir at room temperature for 60 hours. It was then adjusted to a pH of approximately 7 by addition of 20percent aqueous sodium hydroxide solution, and extracted with dichloromethane (3 x 1 L). The combined organic layers were dried, filtered, and concentrated in vacuo; purification via silica gel chromatography (Gradient: 0percent to 10percent ethyl acetate in petroleum ether) afforded the product as a yellow solid. Yield: 70 g, 0.43 mmol, 40percent.1H NMR (400 MHz, CDCI3) δ 9.31 -9.36 (m, 1 H), 8.47-8.52 (m, 1 H), 2.74 (s, 3H)
40% With tetrabutylammonium nitrate; trifluoroacetic anhydride In tert-butyl methyl ether at 20℃; for 60 h; A mixture of 3-methylpyridine-2-carbonitrile (128 g, 1 .08 mol) and tetrabutylammonium nitrate (363 g, 1 .19 mol) in ferf-butyl methyl ether (1 .3 L) was cooled to 4 °C. Trifluoroacetic anhydride (171 mL, 1.21 mol) was added, and the reaction mixture was allowed to stir at room temperature for 60 hours. It was then adjusted to a pH of approximately 7 by addition of 20percent aqueous sodium hydroxide solution, and extracted with dichloromethane (3 x 1 L). The combined organic layers were dried, filtered, and concentrated in vacuo; purification via silica gel chromatography (Gradient: 0percent to 10percent ethyl acetate in petroleum ether) afforded the product as a yellow solid. Yield: 70 g, 0.43 mmol, 40percent.1H NMR (400 MHz, CDCI3) δ 9.36-9.31 (m, 1 H), 8.52-8.47 (m, 1 H), 2.74 (s, 3H).
40% With tetrabutylammonium nitrate; trifluoroacetic anhydride In tert-butyl methyl ether at 4 - 20℃; for 60 h; A mixture of 3-methylpicolinonitrile (046) (128 g, 1.08 mol) and tetrabutylammonium nitrate (363 g, 1.19 mol) in tert-butyl methyl ether (1.3 L) was cooled to 4 00. Trifluoroacetic anhydride (171 mL, 1.21 mol) was added, and the reaction mixture was allowed to stir at room temperature for 60 hours. It was thenadjusted to a pH of approximately 7 by addition of 20percent aqueous sodium hydroxide solution, and extracted with dichloromethane (3 x 1 L). The combined organic layers were dried, filtered, and concentrated in vacuo; purification via silica gel chromatography (Gradient: 0percent to 10percent ethyl acetate in petroleum ether) afforded 3-methyl-5-nitropicolinonitrile as a yellow solid. Yield: 70 g, 0.43 mmol, 40percent. 1H NMR (400 MHz, CDCI3) o 9.31-9.36 (m, 1H), 8.47-8.52 (m, 1H), 2.74 (s, 3H).
40% With tetrabutylammonium nitrate; trifluoroacetic anhydride In tert-butyl methyl ether at 4 - 20℃; for 60 h; A mixture of 3-methylpyridine-2-carbonitrile (128 g, 1.08 mol) and tetrabutylammonium nitrate (363 g, 1.19 mol) in tert-butyl methyl ether (1.3 L) wascooled to 4 °C. Trifluoroacetic anhydride (171 mL, 1.21 mol) was added, and the reaction mixture was allowed to stir at room temperature for 60 hours. It was then adjusted to a pH of approximately 7 by addition of 20percent aqueous sodium hydroxide solution, and extracted with dichloromethane (3 x 1 L). The combined organic layers were dried, filtered, and concentrated in vacuo; purification via silica gelchromatography (Gradient: 0percent to 10percent ethyl acetate in petroleum ether) afforded the product as a yellow solid. Yield: 70 g, 0.43 mmol, 40percent. 1H NMR (400 MHz, CDCI3) ö 9.31 -9.36 (m, 1H), 8.47-8.52 (m, 1H), 2.74 (5, 3H).

Reference: [1] Bioorganic and Medicinal Chemistry, 1999, vol. 7, # 9, p. 1845 - 1855
[2] Patent: WO2015/155626, 2015, A1, . Location in patent: Page/Page column 89; 90
[3] Patent: WO2017/51294, 2017, A1, . Location in patent: Page/Page column 57; 58
[4] Patent: WO2017/51303, 2017, A1, . Location in patent: Page/Page column 72; 73
[5] Patent: WO2017/51276, 2017, A1, . Location in patent: Page/Page column 99
[6] Patent: WO2011/103202, 2011, A2, . Location in patent: Page/Page column 159
  • 30
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YieldReaction ConditionsOperation in experiment
19% With trifluoroacetic anhydride In tert-butyl methyl ether (a)
3-Methyl-5-nitro-pyridine-2-carbonitrile.
To a white suspension of 2-cyano-3-methylpyridine (6.08 g, 51.5 mmol), tetrabutylammonium nitrate (21.0 g, 69.0 mmol) in tert-butyl methyl ether (150 mL) at 0° C. was slowly added trifluoroacetic anhydride (9.6 mmol, 69.0 mmol).
The white suspension was stirred at 0° C. for 2 h and then equilibrated to room temperature and stirred overnight.
The resulting yellow solution was poured into 3M NaOH (300 mL), extracted with CH2Cl2 (300 mL), dried over Na2SO4, and then the solvent was removed by evaporation.
The residue was purified by flash column chromatography (silica gel, elution with EtOAc:hexanes, 1:3.5), to give 1.65 g (19percent) of the title compound as a white solid. 1H NMR (CDCl3): 9.33 (d, 1H, J=2.4 Hz), 8.50 (d, 1H, J=2.4 Hz), 2.74 (s, 3H).
Reference: [1] Journal of Medicinal Chemistry, 2018, vol. 61, # 10, p. 4476 - 4504
[2] Patent: US2004/77605, 2004, A1,
[3] Patent: US2004/127521, 2004, A1,
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  • [ 5912-34-5 ]
Reference: [1] Journal of Medicinal Chemistry, 2011, vol. 54, # 13, p. 4735 - 4751
[2] Patent: WO2009/155121, 2009, A2,
  • 32
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  • [ 38092-89-6 ]
Reference: [1] Journal of Organic Chemistry, 1989, vol. 54, # 9, p. 2242 - 2244
[2] Journal of Organic Chemistry, 1989, vol. 54, # 9, p. 2242 - 2244
[3] Journal of Organic Chemistry, 1989, vol. 54, # 9, p. 2242 - 2244
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  • [ 5912-35-6 ]
Reference: [1] Journal of Medicinal Chemistry, 2011, vol. 54, # 13, p. 4735 - 4751
[2] Patent: WO2009/155121, 2009, A2,
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  • [ 125903-77-7 ]
Reference: [1] Journal of Medicinal Chemistry, 1990, vol. 33, # 4, p. 1230 - 1241
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  • [ 79794-75-5 ]
Reference: [1] Journal of Organic Chemistry, 1989, vol. 54, # 9, p. 2242 - 2244
[2] Journal of Organic Chemistry, 1989, vol. 54, # 9, p. 2242 - 2244
[3] Journal of Organic Chemistry, 1989, vol. 54, # 9, p. 2242 - 2244
  • 36
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  • [ 116986-13-1 ]
YieldReaction ConditionsOperation in experiment
65% With N-Bromosuccinimide In tetrachloromethane for 16 h; Reflux EXAMPLE 75; N-Cl-chloro-S-Cl^-naphthyridin-δ-y^pyridin-S-yl)^- fluorobenzenesulfonamide; (1) 3-(bromomethyl)picolinonitrile.; (Some starting materials may be obtained from TCI America, Wellesley, MA) To a 100 mL round-bottomed flask was added 3- methylpicolinonitrile (2.36 g, 20.0 mmol), NBS (7.82 g, 43.9 mmol), and CCl4 (50 mL). The reaction mixture was stirred at reflux for 16 h. The mixture was cooled to room temperature. The solid was filtered and washed with 50percent EtOAc/hexanes. The solvent was removed in vacuo and the residue was purified by silica gel chromatography, eluting with 30percent EtOAc/hexane to give 3- (bromomethyl)picolinonitrile (2.56 g, 65.0percent yield). MS (ESI pos. ion) m/z calc'd for CvH5BrN2: 196.0, 198.0; found 197.0, 199.0. 1H NMR (300 MHz, CHLOROFORM-;/) δ ppm 4.64 (s, 2 H) 7.54 (dd, J=8.04, 4.68 Hz, 1 H) 7.92 (dd, J=8.04, 1.61 Hz, 1 H) 8.66 (dd, J=4.75, 1.53 Hz, 1 H)
63% With N-Bromosuccinimide; dibenzoyl peroxide In tetrachloromethaneReflux A mixture of 3-methylpicolinonitrile (2 g, 16.9 mmol, 1.0 eq), NBS (3 g, 16.9 mmol, 1.0 eq) and BPO (41 1 mg, 1.7 mmol, 0.1 eq) in CCU (30 mL) was refluxed and stirred overnight. Then the mixture was cooled to rt and concentrated. The residue was diluted with water (50 mL), extracted with DCM (50 mLx3). The combined organic layers were washed with brine (20 mL), dried over anhydrous Na2S04 and concentrated. The residue was purified on silica gel column (PE/EtOAc = 5/1) to afford 3-(bromomethyl)picolinonitrile as a brown solid (2.1 g, 63percent).
46% With N-Bromosuccinimide; dibenzoyl peroxide In tetrachloromethane at 80℃; for 2 h; EXAMPLE 1; 3-Cycloheptyl-8-((2,6-dichlorophenoxy)methyl)H-imidazo[1,5-a]pyridine; Compound 1A: 3-(Bromomethyl)picolinonitrile
To a solution of 3-methylpicolinonitrile (660 mg, 5.6 mmol) in 20 mL of carbon tetrachloride was added NBS (1 g, 5.6 mmol) and dibenzoyl peroxide (200 mg, 0.83 mmol) at RT.
The reaction mixture was heated at 80° C. for 2 hr, and then cooled to RT.
The resulting solid was filtered off, and the filtrate was concentrated under reduced pressure to provide a residue.
The residue was diluted with ethyl acetate, washed with water, dried over Na2SO4 and concentrated under reduced pressure to provide crude material.
The crude material was purified via silica gel chromatography (10percent ethyl acetate in hexanes) to provide compound 1A (510 mg, 46percent) as a pale yellow oil. HPLC Rt (Method A): 1.72 min. LC/MS (m/z)=197 (M+H)+.
37% at 87℃; for 5 h; To a 500 mL single-neck round bottom flash fitted with a reflux condenser and a nitrogen outlet was added 10.1 g (86 mmol) 3-methylpicolinonitrile, 200 mL dimethyl carbonate, 18.2 g (103 mmol) N-bromosuccinimide and 2.1 g (8.5 mmol) benzoyl peroxide. The resulting reaction mixture was heated to 87 °C and stirred for 5 h. Following this duration, the reaction mixture was cooled to ambient temperature and filtered, and the solid was rinsed with Et20. DCM was subsequently added to the filtrate and the resulting mixture was filtered. The combined organics were concentrated and the resulting semi-solid was purified by silica gel chromatography (2 x 330 g column, 5-35percent EtOAc/Hexane) followed by reverse-phase HPLC (Waters Xbridge Prep C18 10 μητι OBD, 50 x 250 mm column) to afford the title compound as a yellow solid (6.3 g, 32.0 mmol, 37percent yield). LC-MS m/z 196.8 (M+H)+, 0.60 min (ret. time).

Reference: [1] Journal of Medicinal Chemistry, 2011, vol. 54, # 13, p. 4735 - 4751
[2] Patent: WO2009/155121, 2009, A2, . Location in patent: Page/Page column 126-127
[3] Patent: WO2015/103317, 2015, A1, . Location in patent: Page/Page column 184; 185
[4] Patent: US2006/281750, 2006, A1, . Location in patent: Page/Page column 26
[5] ACS Medicinal Chemistry Letters, 2011, vol. 2, # 8, p. 559 - 564
[6] Patent: WO2018/109649, 2018, A1, . Location in patent: Page/Page column 185
[7] Organic Letters, 2017, vol. 19, # 14, p. 3895 - 3898
[8] Chemical and Pharmaceutical Bulletin, 1981, vol. 29, # 12, p. 3515 - 3521
[9] Journal of Heterocyclic Chemistry, 1993, vol. 30, # 2, p. 473 - 476
[10] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 1, p. 262 - 266
[11] Journal of Medicinal Chemistry, 2011, vol. 54, # 17, p. 6106 - 6116
[12] Patent: US2014/18360, 2014, A1, . Location in patent: Paragraph 0111
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Reference: [1] Patent: US5422351, 1995, A,
[2] Patent: US5430032, 1995, A,
[3] Patent: US5514687, 1996, A,
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Reference: [1] Patent: WO2009/155156, 2009, A1,
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Reference: [1] Patent: WO2015/155626, 2015, A1,
[2] Patent: WO2017/51294, 2017, A1,
[3] Patent: WO2017/51303, 2017, A1,
[4] Patent: WO2017/51276, 2017, A1,
[5] Journal of Medicinal Chemistry, 2018, vol. 61, # 10, p. 4476 - 4504
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  • [ 20970-75-6 ]
  • [ 1201924-31-3 ]
Reference: [1] Patent: WO2009/155156, 2009, A1,
[2] Patent: WO2015/94912, 2015, A1,
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  • [ 20970-75-6 ]
  • [ 1201924-32-4 ]
Reference: [1] Patent: WO2009/155156, 2009, A1,
  • 45
  • [ 20970-75-6 ]
  • [ 937648-82-3 ]
YieldReaction ConditionsOperation in experiment
97% at 20 - 80℃; for 0.416667 h; Example 8rac-N-(((2S,3R)-3 -Methyl-i -(2-methyl-S -phenylthiazole-4-carbonyl)piperidin-2- ylmethyliuinoline-8-carboxamide3 -MethylpicolinamideLN_I,NH20A mixture of 3-methylpicolinonitrile (2.36 g, 20 mmol) and conc. sulfuric acid (12.5mL) was stirred at 80°C for 25 mm. The solution was cooled to r.t., poured into water (80mL), followed by addition of sat. Na2CO3 (aq.) until pH 7. The resulting mixture was extracted with DCM (3x) and the combined organic layer was dried over Mg504 and concentrated in vacuo to provide 3-methylpicolinamide as a white solid (2.65 g, 97percent). ‘H74NMR (CDC13, 400 MHz) ö 8.43 (dd, 1H), 7.93 (brs, 1H), 7.62 (dd, 1H), 7.35 (dd, 1H), 5.44 (brs, 1H), 2.76 (s, 3H).
77% With Acetaldehyde oxime; sodium molybdate dihydrate In water for 16 h; Reflux General procedure: To a 25 mL round-bottom flask equipped with magnetic stirrer were added nitrile (2 mmol), acetaldoxime (6 mmol), sodium molybdate (VI) dihydrate (0.2 mmol) and H2O (10 mL). The mixture was heated to reflux for 5-16 h. After cooling to room temperature, the solution was directly evaporated to dryness and the residue was purified by column chromatography on silica gel (ethylacetate/n-hexane) to give the corresponding amide.
Reference: [1] Patent: WO2013/119639, 2013, A1, . Location in patent: Page/Page column 74; 75
[2] Applied Organometallic Chemistry, 2012, vol. 26, # 7, p. 377 - 382
[3] Synthetic Communications, 2014, vol. 44, # 4, p. 474 - 480
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Reference: [1] Tetrahedron, 2013, vol. 69, # 33, p. 6799 - 6803
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