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Chemical Structure| 86847-59-8
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Product Details of [ 86847-59-8 ]

CAS No. :86847-59-8 MDL No. :MFCD00460277
Formula : C10H14N2O Boiling Point : -
Linear Structure Formula :C5H4N(NHCOC4H9) InChI Key :CGSPVYCZBDFPHJ-UHFFFAOYSA-N
M.W : 178.23 Pubchem ID :1051519
Synonyms :

Calculated chemistry of [ 86847-59-8 ]

Physicochemical Properties

Num. heavy atoms : 13
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.4
Num. rotatable bonds : 3
Num. H-bond acceptors : 2.0
Num. H-bond donors : 1.0
Molar Refractivity : 52.71
TPSA : 41.99 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.96 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.04
Log Po/w (XLOGP3) : 2.01
Log Po/w (WLOGP) : 1.88
Log Po/w (MLOGP) : 0.88
Log Po/w (SILICOS-IT) : 1.57
Consensus Log Po/w : 1.67

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.35
Solubility : 0.787 mg/ml ; 0.00442 mol/l
Class : Soluble
Log S (Ali) : -2.52
Solubility : 0.54 mg/ml ; 0.00303 mol/l
Class : Soluble
Log S (SILICOS-IT) : -3.23
Solubility : 0.104 mg/ml ; 0.000585 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.62

Safety of [ 86847-59-8 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H317-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 86847-59-8 ]

* 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.

  • Upstream synthesis route of [ 86847-59-8 ]
  • Downstream synthetic route of [ 86847-59-8 ]

[ 86847-59-8 ] Synthesis Path-Upstream   1~19

  • 1
  • [ 927-63-9 ]
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  • [ 254-60-4 ]
Reference: [1] Synlett, 2006, # 3, p. 379 - 382
  • 2
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  • [ 7521-41-7 ]
Reference: [1] Journal of Organic Chemistry, 1983, vol. 48, # 20, p. 3401 - 3408
[2] Chemistry Letters, 2018, vol. 47, # 4, p. 400 - 403
  • 3
  • [ 86847-59-8 ]
  • [ 68-12-2 ]
  • [ 7521-41-7 ]
Reference: [1] Synthetic Communications, 2001, vol. 31, # 10, p. 1573 - 1579
  • 4
  • [ 86847-59-8 ]
  • [ 13534-99-1 ]
Reference: [1] Journal of the Chemical Society - Perkin Transactions 1, 1999, # 11, p. 1505 - 1510
  • 5
  • [ 86847-59-8 ]
  • [ 23612-48-8 ]
Reference: [1] Journal of Organic Chemistry, 1988, vol. 53, # 12, p. 2740 - 2744
  • 6
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  • [ 1569-17-1 ]
  • [ 1569-16-0 ]
Reference: [1] Synlett, 2006, # 3, p. 379 - 382
  • 7
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  • [ 1569-16-0 ]
Reference: [1] Chemistry Letters, 2018, vol. 47, # 4, p. 400 - 403
  • 8
  • [ 504-29-0 ]
  • [ 3282-30-2 ]
  • [ 86847-59-8 ]
YieldReaction ConditionsOperation in experiment
100% With triethylamine In dichloromethane at 0℃; for 2 h; Preparation Example J-1.
2,2-Dimethyl-N-pyridin-2-yl-propionamide
2-Aminopyridine (3.1g, 33mmol) and triethylamine(6.9mL, 49mmol) was dissolved in dichloromethane (40mL), 2,2-dimethylpropionyl chloride (4.5mL, 36mmol) was added on an ice bath, and the solution was stirred for 2 hours at the same temperature.
Water was added thereto for extraction, the organic layer was sequentially washed with an aqueous solution of saturated sodium bicarbonate and brine, then, dried over anhydrous magnesium sulfate.
The solvent was evaporated in vacuo, and the title compound (6.0g, 34mmol, 102percent) was obtained as a white solid.
1H-NMR Spectrum (CDCl3) δ (ppm):1.27 (9H, s), 7.03 (1 H, ddd, J=1.1, 4.9, 7.3Hz), 7.68-7.72 (1 H, m), 8.02 (1 H, s), 8.23-8.27 (2H, m).
100% With triethylamine In dichloromethane at 0 - 20℃; for 18 h; To a solution of 2-aminopyridine (94.12 g, 1 mote) and Et3N (167.3 mL, 1.2 mole) in CH2Cl2 (1 L) was added pivaloyl chloride (135.5 mL, 1.1 mole) dropwise at 0 °C. The mixture was allowed to warm to RT as the bath warmed. After 18 hr the mixture was filtered. The filtrate was washed sequentially with H2O (1.5 L) and saturated NaHCO3 (2 .x. 1.5 L), then was dried (MgSO4)and concentrated under reduced pressure to give the title compound (183 g, 103percent) as an off-white solid: 1H NMR (300 MHz, CDCl3) δ 8.28 (m, 2 H), 8.00 (br s, 1 H), 7.70 (m, 1 H), 7.03 (m, 1 H), 1.31 (s, 9 H); MS (ES) m/e 179 (M + H)+. Note: 1H NMR showed the presence of a small amount of tert-butyl containing impurities, but the material is pure enough for use in the next step.
100% With triethylamine In dichloromethane at 0℃; for 2 h; 2-Aminopyridine (3.1g, 33mmol) and triethylamine(6.9mL, 49mmol) was dissolved in dichloromethane (40mL), 2,2-dimethylpropionyl chloride (4.5mL, 36mmol) was added on an ice bath, and the solution was stirred for 2 hours at the same temperature. Water was added thereto for extraction, the organic layer was sequentially washed with an aqueous solution of saturated sodium bicarbonate and brine, then, dried over anhydrous magnesium sulfate. The solvent was evaporated in vacuo, and the title compound (6.0g, 34mmol, 102percent) was obtained as a white solid. 1H-NMR Spectrum (CDCl3) δ(ppm) :1.27 (9H, s), 7.03 (1H, ddd, J=1.1, 4.9, 7.3Hz), 7.68-7.72 (1 H, m), 8.02 (1 H, s), 8.23-8.27 (2H, m).
98% With triethylamine In dichloromethane at 0 - 20℃; for 4.5 h; To a solution of 2-aminopyridine (50.0 g, 531 mmol) in methylene chloride (500 mL) were added triethylamine (81.4 mL, 584 mmol) and pivaloyl chloride (71.9 mL, 584 mmol) at 0° C., which was stirred for 4 hours and 30 minutes at room temperature. The reaction solution was partitioned into water and methylene chloride. The organic layer was washed with water and saturated aqueous sodium chloride, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under a reduced pressure. To a solution of the resulting residue in methanol (300 mL) was added potassium carbonate (73.4 g, 531 mmol) at 0° C., which was stirred for 90 minutes at room temperature. The reaction solution was partitioned into water and ethyl acetate at room temperature. The organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate, and the solvent was evaporated under a reduced pressure. Heptane (300 mL) was added to the residue, and the precipitated solids were filtered to obtain the title compound (80.2 g, 85percent). The filtrate was then concentrated under a reduced pressure, and the residue was purified by silica gel column chromatography (heptane:ethyl acetate=2:1) to obtain the title compound (12.2 g, 13percent). 1H-NMR Spectrum (DMSO-d6) δ (ppm): 1.22 (9H, s), 7.06-7.09 (1H, m), 7.72-7.77 (1H, m), 8.01-8.03 (1H, m), 8.29-8.31 (1H, m), 9.71 (1H, s).
91% With triethylamine In dichloromethane at -5 - 20℃; for 2.25 h; N-(pyridin-2-yl)pivalamide
2-Aminopyridine (25.00 g, 265.6 mmole) was taken up under nitrogen in DCM (425 ml) and NEt3 (46.00 ml, 332 mmole) was added.
The solution was cooled to -5° C., a solution of trimethyl acetyl chloride (35.95 ml, 292.20 mmole) in DCM (50 ml) was added dropwise and the mixture was stirred for a further 15 minutes at -5° C.
The mixture was then stirred for 2 hours at RT.
The suspension was washed with H2O (200 ml), then with dilute NaHCO3 solution, and the organic phase was dried over MgSO4.
After filtering off the drying agent and removing the solvent on a rotary evaporator, the residue (48.30 g) was recrystallized from hexane (100 ml) at boiling heat. N-(pyridin-2-yl)pivalamide (42.80 g, 91percent) was obtained in the form of colourless crystals.
91% Inert atmosphere; Cooling Step 1 : Synthesis of N-o-pyridylpivalamide In a 100 mL flask, 2-aminopyridine (3.0 g, 0.032 mol, 1 eq) was dissolved in 35 mL of dichloromethane. After addition of triethylamine (3.6 g, 0.035 mol, 1 .1 eq), the solution was cooled in a water bath and trimethylacetylchloride (4.31 mL, 0.035 mol, 1 .1 eq) was added dropwise. This mixture was stirred overnight under inert atmosphere. The reaction mixture was then 2 times washed with saturated sodium carbonate solution (30 mL) and brine (30 mL). After drying on magnesium sulfate the desired product was obtained as a powder by removing the organic solvent under reduced pressure (5.2 g, 0.029 mol, 91 percent). Bruto formula: Ci0H14N2O. MW.: 178.27 g/mol. 1H-NMR (300 MHz, CDCI3): δ (ppm) = 1 .23 (s, 9H, C(CH3)3), 6.93 (m, 1 H, ArH), 7.60 (m, 1 H, ArH), 8.01 (s, 1 H, NH), 8.17 (m, 2H, ArH).
84% With triethylamine In dichloromethane at 0 - 20℃; for 13 h; To a solution of A (11 g, 116 mmol) in dry DCM (100 ml) was added Et3N (14.7 g, 145 mmol) and a solution of pivaloyl chloride (15.3 g, 128 mmol) in dry DCM (20 ml) at 0°C. Reaction mixture was stirred at 0°C for lh, then warmed to room temperature and stirred for 12 h under nitrogen, monitored by TLC. Cold water (50 ml) was added, and the mixture extracted with DCM, washed with Sat. aq. NaHC03, water and brine, then dried and concentrated. The crude material was purified by column chromatography (silica gel, EtOAc:PE=l :2) to give B (12 g, 84percent) as a white solid.
67% With triethylamine In dichloromethane at 0 - 20℃; for 3 h; To a solution of 1.88 g (20.0 mmol, 1 eq.) of 2-aminopyridine and 3.6 mL (26.0 mmol, 1.3 eq.) of triethylamine in 30 mL of DCM, cooled to 0°C, were added 2.7 mL (22.0 mmol, 1.1 eq.) of trimethylacetyl chloride in 4 mL of DCM. After 2 hours, the mixture was stirred one hour at room temperature. Then, 40 mL of water were added. The aqueous layer was extracted with 20 mL of dichloromethane. The organic phase was washed with 20 mL of aqueous NaHC03, dried, filtered and concentrated. Purification over silica gel provided 2.40 g (13.5 mmol, 67percent) of the title compound as a white solid. Rf=0.49 (PE/EtOAc 2:1 ). 1H NMR (300 MHz): δ = 8.24 (m, 2 H), 8.00 (broad, 1 H), 7.67 (t, J = 7.9 Hz, 1 H), 7.01 (m, 1 H), 1 .31 (s, 9 H) ppm. 13C NMR (75 MHz): δ = 177.2, 151.7, 147.8, 138.4, 1 19.8, 1 14.0, 39.9, 27.6 ppm
67% With triethylamine In dichloromethane at 0 - 20℃; for 3 h; To a solution of 1.88 g (20.0 mmol, 1 eq.) of 2-aminopyridine and 3.6 mL (26.0 mmol, 1.3 eq.) of triethylamine in 30 mL of DCM, cooled to 0°C, were added 2.7 mL (22.0 mmol, 1.1 eq.) of trimethylacetyl chloride in 4 mL of DCM. After 2 hours, the mixture was stirred one hour at room temperature. Then, 40 mL of water were added. The aqueous layer was extracted with 20 mL of dichloromethane. The organic phase was washed with 20 mL of aqueous NaHC03, dried, filtered and concentrated. Purification over silica gel provided 2.40 g (13.5 mmol, 67percent) of the title compound as a white solid. Rf=0.49 (PE/EtOAc 2:1 ). 1H NMR (300 MHz): δ = 8.24 (m, 2 H), 8.00 (broad, 1 H), 7.67 (t, J = 7.9 Hz, 1 H), 7.01 (m, 1 H), 1.31 (s, 9 H) ppm. 13C NMR (75 MHz): δ = 177.2, 151.7, 147.8, 138.4, 119.8, 114.0, 39.9, 27.6 ppm
13%
Stage #1: With triethylamine In dichloromethane at 0 - 20℃; for 4.5 h;
Stage #2: With potassium carbonate In methanol at 0 - 20℃; for 1.5 h;
Manufacturing Example 39-1-1 2,2-Dimethyl-N-pyridin-2-yl-propionamide; To a solution of 2-aminopyridine (50.0 g, 531 mmol) in methylene chloride (500 mL) were added triethylamine (81.4 mL, 584 mmol) and pivaloyl chloride (71.9 mL, 584 mmol) at 0° C., which was stirred for 4 hours and 30 minutes at room temperature. The reaction solution was partitioned into water and methylene chloride. The organic layer was washed with water and saturated aqueous sodium chloride, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under a reduced pressure. To a solution of the resulting residue in methanol (300 mL) was added potassium carbonate (73.4 g, 531 mmol) at 0° C., which was stirred for 90 minutes at room temperature. The reaction solution was partitioned into water and ethyl acetate at room temperature. The organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate, and the solvent was evaporated under a reduced pressure. Heptane (300 mL) was added to the residue, and the precipitated solids were filtered to obtain the title compound (80.2 g, 85percent). The filtrate was then concentrated under a reduced pressure, and the residue was purified by silica gel column chromatography (heptane:ethyl acetate=2:1) to obtain the title compound (12.2 g, 13percent).1H-NMR Spectrum (DMSO-d6) δ (ppm): 1.22 (9H, s), 7.06-7.09 (1H, m), 7.72-7.77 (1H, m), 8.01-8.03 (1H, m), 8.29-8.31 (1H, m), 9.71 (1H, s).
13% With triethylamine In dichloromethane at 0 - 20℃; for 4.5 h; Manufacturing Example 1-2-1
2,2-Dimethyl-N-pyridin-2-yl-propionamide
To a methylene chloride solution (500 mL) of 2-aminopyridine (50.0 g, 531 mmol) were added triethylamine (81.4 mL, 584 mmol) and pivaloyl chloride (71.9 mL, 584 mmol) at 0° C., which was stirred for 4 hours and 30 minutes at room temperature.
The reaction solution was partitioned into water and methylene chloride.
The organic layer was washed with water and saturated brine and dried over anhydrous magnesium sulfate, and the solvent was evaporated under a reduced pressure.
Potassium carbonate (73.4 g, 531 mmol) was added to 300 mL of thus obtained residue methanol solution at 0° C., which was stirred at room temperature for 90 minutes.
This reaction solution was partitioned into water and ethyl acetate.
The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, the solvent was evaporated under a reduced pressure.
Heptane (300 mL) was added to the residue, the precipitated solids were collected by filtering, which gave the titled compound (80.2 g, 85percent).
The filtrate was then concentrated under a reduced pressure, and the residue was purified by silica gel column chromatography (heptane:ethyl acetate=2:1), which gave the titled compound (12.2 g, 13percent).
1H-NMR spectrum (DMSO-d6) δ (ppm): 1.22 (9H, s), 7.06-7.09 (1H, m), 7.72-7.77 (1H, m), 8.01-8.03 (1H, m), 8.29-8.31 (1H, m), 9.71 (1H, s).

Reference: [1] Patent: EP1782811, 2007, A1, . Location in patent: Page/Page column 59
[2] Patent: EP1218005, 2004, B1, . Location in patent: Page 21
[3] Patent: EP1669348, 2006, A1, . Location in patent: Page/Page column 67
[4] Organic Letters, 2013, vol. 15, # 13, p. 3460 - 3463
[5] Chemistry - A European Journal, 2010, vol. 16, # 27, p. 7992 - 7995
[6] Patent: US2007/105904, 2007, A1, . Location in patent: Page/Page column 84
[7] Journal of Medicinal Chemistry, 2018, vol. 61, # 12, p. 5162 - 5186
[8] Synthetic Communications, 2001, vol. 31, # 10, p. 1573 - 1579
[9] Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 1, p. 114 - 125
[10] Patent: US2009/156593, 2009, A1, . Location in patent: Page/Page column 17
[11] Patent: WO2015/18928, 2015, A1, . Location in patent: Page/Page column 183-184
[12] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1999, vol. 38, # 3, p. 257 - 259
[13] European Journal of Medicinal Chemistry, 2005, vol. 40, # 1, p. 15 - 23
[14] Tetrahedron Letters, 1998, vol. 39, # 23, p. 4103 - 4106
[15] Journal of Physical Chemistry A, 2010, vol. 114, # 38, p. 10421 - 10426
[16] Patent: US6344/449, 2002, B1, . Location in patent: Example A3a)
[17] Patent: US6344449, 2002, B1, . Location in patent: Example A3a)
[18] Patent: WO2014/190199, 2014, A1, . Location in patent: Paragraph 00277
[19] Journal of Organic Chemistry, 1983, vol. 48, # 20, p. 3401 - 3408
[20] Patent: WO2014/198844, 2014, A1, . Location in patent: Page/Page column 13; 14
[21] Patent: WO2014/198848, 2014, A2, . Location in patent: Page/Page column 12; 13
[22] Patent: US2009/82403, 2009, A1, . Location in patent: Page/Page column 86
[23] Patent: US2010/331282, 2010, A1, . Location in patent: Page/Page column 10
[24] Tetrahedron, 2007, vol. 63, # 41, p. 10354 - 10362
[25] Tetrahedron Letters, 2007, vol. 48, # 27, p. 4707 - 4710
[26] Patent: US6127369, 2000, A,
[27] Patent: US4866074, 1989, A,
[28] Patent: EP2065377, 2009, A1, . Location in patent: Page/Page column 59-60
[29] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 7, p. 2006 - 2008
[30] Patent: US2008/275244, 2008, A1, . Location in patent: Page/Page column 4
[31] Tetrahedron Letters, 2017, vol. 58, # 1, p. 1 - 4
[32] Journal of Organic Chemistry, 2017, vol. 82, # 18, p. 9410 - 9417
[33] Chemistry Letters, 2018, vol. 47, # 4, p. 400 - 403
  • 9
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YieldReaction ConditionsOperation in experiment
88% With potassium carbonate In 1,4-dioxane at 80℃; Heating / reflux EXAMPLE 10Coupling of 2-chloropyridine with 2,2-dimethylpropionamide (catalyst: Pd(OAc)2/2,2-dimethyl-1,3-bis(diphenylphosphino)propane)3.1 g of potassium carbonate (22.7 mmol), 2.0 g of 2,2-dimethylpropionamide (20.0 mmol) and 1.7 g of 2-chloropyridine (14.2 mmol) are dissolved or suspended in 40 ml of dioxane and admixed at 80° C. with a suspension of 0.027 g of palladium(II) acetate (0.9 mol percent) and 0.156 g of 2,2-dimethyl-1,3-bis(diphenylphosphino)propane (2.5 mol percent). The mixture is subsequently refluxed and the conversion is monitored by HPLC. After boiling overnight, the conversion is >98percent. The work-up is carried out by addition of water to dissolve the precipitated salts, addition of toluene and phase separation. The upper, product-containing phase is evaporated on a rotary evaporator and the product is purified by chromatography. This gave 2.6 g (88percent) of coupling product (2,2-dimethyl-N-pyridin-2-yl-propionamide)
85% With potassium carbonate In 1,4-dioxane at 80℃; Heating / reflux EXAMPLE 12Coupling of 2-chloropyridine with 2,2-dimethylpropionamide (catalyst: Pd(OAc)2/1,2-bis(diphenylphosphino)ethane)As example 10, but 0.151 g of 1,4-bis(diphenylphosphino)ethane (2.5 mol percent) is used instead of 0.141 g of 2,2-dimethyl-1,3-bis(diphenylphosphino)propane (2.5 mol percent). Yield: 2.5 g (85percent).
81% With potassium carbonate In 1,4-dioxane at 80℃; Heating / reflux EXAMPLE 11Coupling of 2-chloropyridine with 2,2-dimethylpropionamide (catalyst: Pd(OAc)2/1,4-bis(diphenylphosphino)butane)As example 10, but 0.151 g of 1,4-bis(diphenylphosphino)butane (2.5 mol percent) was used instead of 0.156 g of 2,2-dimethyl-1,3-bis(diphenylphosphino)propane (2.5 mol percent). Yield: 2.4 g (81percent).
Reference: [1] Patent: US2008/39633, 2008, A1, . Location in patent: Page/Page column 5
[2] Patent: US2008/39633, 2008, A1, . Location in patent: Page/Page column 5
[3] Patent: US2008/39633, 2008, A1, . Location in patent: Page/Page column 5
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YieldReaction ConditionsOperation in experiment
84% for 0.166667 h; General procedure: The appropriate aminopyridine-N-oxide (13, 1.00 equiv) and carboxylic acid/acid chloride (14, 1.20 equiv) were combined in DMF (0.50 M) and treated with i-Pr2EtN (2.5equiv) and HATU (1.2 equiv). The reaction was stirred at r.t.until the initial coupling was deemed complete by LC–MS(usually 1–2 h). The reaction was then treated with tetrahydroxydiboron (5, 2.00 equiv) in a single portion (Note: exotherm evident). After stirring for 10 min, the reaction was quenched with H2O (10 mL), which resulted in the precipitation of most products. The solids were filtered,washed with H2O, and air-dried to afford the desired products in sufficient purity. For those reactions where precipitation of solid was not evident, the desired products were extracted with EtOAc (3 × 10 mL), washed with brine,dried (Na2SO4), and evacuated. These crude materials were purified by silica gel column chromatography.
Reference: [1] Synlett, 2013, vol. 24, # 20, p. 2695 - 2700
[2] Organic Letters, 2017, vol. 19, # 18, p. 4830 - 4833
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Reference: [1] RSC Advances, 2015, vol. 5, # 14, p. 10567 - 10574
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  • [ 754-10-9 ]
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Reference: [1] Chemistry - A European Journal, 2010, vol. 16, # 18, p. 5437 - 5442
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Reference: [1] Organic Letters, 2013, vol. 15, # 13, p. 3460 - 3463
  • 14
  • [ 111098-28-3 ]
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  • [ 121953-52-4 ]
Reference: [1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1989, p. 639 - 642
  • 15
  • [ 590-28-3 ]
  • [ 630-18-2 ]
  • [ 107264-09-5 ]
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Reference: [1] Tetrahedron Letters, 1994, vol. 35, # 2, p. 207 - 210
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Reference: [1] Synlett, 2013, vol. 24, # 20, p. 2695 - 2700
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Reference: [1] Tetrahedron, 1995, vol. 51, # 2, p. 635 - 648
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  • [ 86847-59-8 ]
  • [ 113975-31-8 ]
YieldReaction ConditionsOperation in experiment
94%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78 - -55℃; for 1 h;
Stage #2: With iodine In tetrahydrofuran; hexane at -65 - 0℃; for 2 h;
A cold solution (-78° C.) of 2-pivaloylamino-pyridine (6a, 500 g, 2.8 mol) in tetrahydrofuran (6 L) was treated with n-butyllithium (2.5 M in hexanes, 2.25 L, 5.63 mol) at a rate such that the temperature did not exceed -55° C. The mixture was stirred for 1 hour until metallation was determined to be complete. A solution of iodine (782 g, 3.01 mol) in tetrahydrofuran (1 L) was added at a rate that the temperature did not exceed -65° C. Upon complete addition, the reaction was stirred for 2 hours and the reaction mixture was slowly poured into ice water (6 L). The mixture was diluted with ethyl acetate (6 L) and the layers separated. The aqueous was washed with ethyl acetate (4 L) and then the combined organics washed with a solution of sodium thiosulfate in water (200 g per liter, 3.x.4 L) followed by washing with aqueous saturated sodium chloride solution (2.x.4 L). The organics were dried over sodium sulfate and solvent removed under reduced pressure to yield 7a as a tan to brown solid of sufficient purity to take into the next step. Yield: 800 g, 94percent.
61%
Stage #1: With n-butyllithium; N,N,N,N,-tetramethylethylenediamine In tetrahydrofuran; hexane at -75 - -10℃; for 2.25 h;
Stage #2: With iodine In tetrahydrofuran; hexane at -75℃; for 2 h;
N-(3-iodopyridin-2-yl)pivalamide
N-(pyridin-2-yl)pivalamide (14.25 g, 80 mmole) and TMEDA (29.80 ml, 200 mmole) were dissolved in THF (400 ml) under nitrogen and n-BuLi (125 ml, 200 mmole; 1.6 M solution in n-hexane) was added dropwise at -75° C.
The mixture was stirred for 15 minutes at -75° C. and then for 2 hours at -10° C.
After renewed cooling to -75° C. a solution of iodine (50.76 g, 200 mmole) in THF (200 ml) was added dropwise and the reaction mixture was stirred for 2 hours.
The mixture was heated to 0° C. and quenched with saturated aqueous sodium thiosulfate solution.
The aqueous phase was extracted with DCM (2*150 ml) and the combined organic phases were dried over MgSO4.
After filtering off the drying agent and removing the solvent on a rotary evaporator, the residue was purified by column chromatography (ether: cyclohexane=3:1) and N-(3-iodopyridin-2-yl)pivalamide (14.80 g, 61percent) was thereby obtained.
57%
Stage #1: With n-butyllithium; N,N,N,N,-tetramethylethylenediamine In tetrahydrofuran; hexane at -78 - 0℃;
Stage #2: With iodine In tetrahydrofuran; hexane at -78 - 0℃; for 1.5 h;
Manufacturing Example 39-1-2 N-(3-Iodo-pyridin-2-yl)-2,2-dimethyl-propionamide; To a mixture of 2,2-dimethyl-N-pyridin-2-yl-propionamide (3.0 g, 17 mmol) described in Manufacturing Example 39-1-1, N,N,N',N'-tetramethylethylenediamine (6.3 mL, 42 mmol) and tetrahydrofuran (60 mL) was added dropwise n-butyl lithium (1.6 M n-hexane solution, 30 mL, 47 mmol) at -78° C., which was stirred overnight at 0° C. Iodine (6.8 g, 27 mmol) was added to the reaction mixture at -78° C., and stirred for 1.5 hours at 0° C. Water and saturated aqueous sodium thiosulfate solution were added to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, and the solvent was evaporated under a reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:heptane=2:1) to obtain the title compound (2.9 g, 57percent).1H-NMR Spectrum (CDCl3) δ (ppm): 1.38 (9H, s), 6.85 (1H, dd, J=4.8, 7.9 Hz), 7.94 (1H, brs), 8.11 (1H, dd, J=1.7, 7.9 Hz), 8.46 (1H, dd, J=1.7, 4.6 Hz).
57%
Stage #1: With n-butyllithium; N,N,N,N,-tetramethylethylenediamine In tetrahydrofuran; hexane at -78 - 0℃;
Stage #2: With iodine In tetrahydrofuran; hexane at -78 - 0℃; for 1.5 h;
To a mixture of 2,2-dimethyl-N-pyridin-2-yl-propionamide (3.0 g, 17 mmol) described in Manufacturing Example 39-1-1, N,N,N',N'-tetramethylethylenediamine (6.3 mL, 42 mmol) and tetrahydrofuran (60 mL) was added dropwise n-butyl lithium (1.6 M n-hexane solution, 30 mL, 47 mmol) at -78° C., which was stirred overnight at 0° C. Iodine (6.8 g, 27 mmol) was added to the reaction mixture at -78° C., and stirred for 1.5 hours at 0° C. Water and saturated aqueous sodium thiosulfate solution were added to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, and the solvent was evaporated under a reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:heptane=2:1) to obtain the title compound (2.9 g, 57percent). 1H-NMR Spectrum (CDCl3) δ (ppm): 1.38 (9H, s), 6.85 (1H, dd, J=4.8, 7.9 Hz), 7.94 (1H, brs), 8.11 (1H, dd, J=1.7, 7.9 Hz), 8.46 (1H, dd, J=1.7, 4.6 Hz).
57%
Stage #1: With n-butyllithium; N,N,N,N,-tetramethylethylenediamine In tetrahydrofuran; hexane at -78 - 0℃;
Stage #2: With iodine In tetrahydrofuran; hexane at -78 - 0℃;
Manufacturing Example 1-2-2
N-(3-Iodo-pyridin-2-yl)-2,2-dimethyl-propionamide
To a mixture of 2,2-dimethyl-N-pyridin-2-yl-propionamide (3.0 g, 17 mmol) described in Manufacturing Example 1-2-1, N,N,N',N'-tetramethylethylenediamine (6.3 mL, 42 mmol), and tetrahydrofuran (60 mL) was added n-butyl lithium (30 mL, 47 mmol; in a 1.6 M n-hexane solution) dropwise at -78° C., which was stirred overnight at 0° C. Iodine (6.8 g, 27 mmol) was added at -78° C. to the reaction mixture, which was stirred for 1.5 hours at 0° C.
Water and a saturated sodium thiosulfate aqueous solution were added to the reaction mixture, and extraction was performed with ethyl acetate.
The organic layer was washed with saturated brine, and the solvent was evaporated under a reduced pressure.
The residue was purified by silica gel column chromatography (ethyl acetate:heptane=2:1), which gave the titled compound (2.9 g, 57percent).
1H-NMR spectrum (CDCl3) δ (ppm): 1.38 (9H, s), 6.85 (1H, dd, J=4.8, 7.9 Hz), 7.94 (1H, brs), 8.11 (1H, dd, J=1.7, 7.9 Hz), 8.46 (1H, dd, J=1.7, 4.6 Hz).

Reference: [1] Patent: US2006/183758, 2006, A1, . Location in patent: Page/Page column 8
[2] Synthesis, 2008, # 13, p. 2049 - 2054
[3] Chemistry - A European Journal, 2010, vol. 16, # 27, p. 7992 - 7995
[4] Journal of the Chemical Society, Perkin Transactions 1, 2000, # 24, p. 4245 - 4249
[5] Patent: US2009/156593, 2009, A1, . Location in patent: Page/Page column 17
[6] Patent: US2009/82403, 2009, A1, . Location in patent: Page/Page column 86
[7] Patent: US2007/105904, 2007, A1, . Location in patent: Page/Page column 84
[8] Patent: US2010/331282, 2010, A1, . Location in patent: Page/Page column 10
[9] Journal of Organic Chemistry, 1988, vol. 53, # 12, p. 2740 - 2744
[10] Patent: EP2065377, 2009, A1, . Location in patent: Page/Page column 60
[11] Patent: US2008/275244, 2008, A1, . Location in patent: Page/Page column 4
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  • [ 86847-59-8 ]
  • [ 5174-90-3 ]
Reference: [1] Patent: US2011/287937, 2011, A1,
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