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[ CAS No. 23003-35-2 ] {[proInfo.proName]}

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3d Animation Molecule Structure of 23003-35-2
Chemical Structure| 23003-35-2
Chemical Structure| 23003-35-2
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Product Details of [ 23003-35-2 ]

CAS No. :23003-35-2 MDL No. :MFCD06655956
Formula : C6H6BrNO Boiling Point : -
Linear Structure Formula :- InChI Key :UHMANLXCLQNQJD-UHFFFAOYSA-N
M.W : 188.02 Pubchem ID :11959101
Synonyms :

Calculated chemistry of [ 23003-35-2 ]

Physicochemical Properties

Num. heavy atoms : 9
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.17
Num. rotatable bonds : 0
Num. H-bond acceptors : 2.0
Num. H-bond donors : 1.0
Molar Refractivity : 38.93
TPSA : 33.12 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) : -6.08 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.78
Log Po/w (XLOGP3) : 1.92
Log Po/w (WLOGP) : 1.86
Log Po/w (MLOGP) : 0.92
Log Po/w (SILICOS-IT) : 2.02
Consensus Log Po/w : 1.7

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.71
Solubility : 0.368 mg/ml ; 0.00196 mol/l
Class : Soluble
Log S (Ali) : -2.24
Solubility : 1.08 mg/ml ; 0.00577 mol/l
Class : Soluble
Log S (SILICOS-IT) : -2.69
Solubility : 0.383 mg/ml ; 0.00204 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.67

Safety of [ 23003-35-2 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H332-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 23003-35-2 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Upstream synthesis route of [ 23003-35-2 ]
  • Downstream synthetic route of [ 23003-35-2 ]

[ 23003-35-2 ] Synthesis Path-Upstream   1~8

  • 1
  • [ 23003-35-2 ]
  • [ 54232-43-8 ]
Reference: [1] Journal of Organic Chemistry, 1996, vol. 61, # 14, p. 4623 - 4633
[2] Patent: WO2014/78690, 2014, A1,
[3] Patent: WO2016/29214, 2016, A1,
[4] Patent: EP3255042, 2017, A2,
  • 2
  • [ 23003-35-2 ]
  • [ 74-88-4 ]
  • [ 24207-22-5 ]
YieldReaction ConditionsOperation in experiment
88.3% With potassium carbonate In acetone b.
2-Bromo-3-methoxy-6-methyl-pyridine.
A stirred mixture of 2-bromo-3-hydroxy-6-methyl-pyridine (7.89 g, 42.0 mmol), potassium carbonate (11.60 g, 83.9 mmol) and iodomethane (8.93 g, 62.9 mmol, 3.92 mL) in acetone (100 mL) was heated under reflux overnight.
The mixture was filtered, evaporated and purified on silica gel (hexane:ethyl acetate, 95:5 to 9:1) to give the desired product as a white solid (7.49 g, 88.3percent).
1H NMR (500 MHz, CDCl3): δ2.46 (s, 3 H), 3.87 (s, 3 H), 7.04 (s, 2 H).
88.3% With potassium carbonate In acetone b.
2-Bromo-3-methoxy-6-methyl-pyridine
A stirred mixture of 2-bromo-3-hydroxy-6-methyl-pyridine (7.89 g, 42.0 mmol), potassium carbonate (11.60 g, 83.9 mmol) and iodomethane (8.93 g, 62.9 mmol, 3.92 mL) in acetone (100 mL) was heated under reflux overnight.
The mixture was filtered, evaporated and purified on silica gel (hexane:ethyl acetate, 95:5 to 9:1) to give the desired product as a white solid (7.49 g, 88.3percent).
1H NMR (500 MHz, CDCl3): δ2.46 (s, 3H), 3.87 (s, 3H), 7.04 (s, 2H).
42% With potassium carbonate In acetone for 2 h; Reflux [0124] To 2-bromo-6-methylpyridin-3-ol (XXXXIV) were added 50 ml of acetone, potassium carbonate (K2CO3) (2.0 g, 14.66 mmol) and iodomethane (684 μl, 10.99 mmol), and the resulting mixture was stirred with reflux for 2 hrs.
After TLC was conducted, the solvent was removed and the mixture was extracted with 60 ml of ethylacetate (EA) and 60 ml of water.
The organic layer was treated with magnesium sulfate (MgSO4) and filtered, and the solution was concentrated and purified through silica gel chromatography (normal hexane : ethylacetate = 10 : 1, v/v) to give the title compound as pale yellow crystals (772 mg, 3.82 mmol, 42 percent).
1H NMR (400 MHz, CDCl3) δ 7.06 (s, 2H), 3.89 (s, 3H), 2.48 (s, 3H).
Reference: [1] Tetrahedron Letters, 1995, vol. 36, # 30, p. 5319 - 5322
[2] Journal of Organic Chemistry, 1996, vol. 61, # 14, p. 4623 - 4633
[3] Patent: US2003/83357, 2003, A1,
[4] Patent: US6515003, 2003, B1,
[5] Patent: EP3255042, 2017, A2, . Location in patent: Paragraph 0122; 0124
[6] Patent: US2003/55071, 2003, A1,
[7] Patent: WO2014/78690, 2014, A1, . Location in patent: Paragraph 00201
[8] Patent: WO2016/29214, 2016, A1, . Location in patent: Page/Page column 148
  • 3
  • [ 1121-78-4 ]
  • [ 23003-35-2 ]
YieldReaction ConditionsOperation in experiment
53.1% With bromine In pyridine; water a.
2-Bromo-3-hydroxy-6-methyl-pyridine.
To a solution of 5-hydroxy-2-methylpyridine (8.80 g, 80.6 mmol) in 125 mL of pyridine was added a solution of bromine (14.18 g, 88.7 mmol) in 50 mL pyridine dropwise.
The temperature of the reaction mixture rose to 40° C. upon completion of addition.
After 1 hour the pyridine was removed under vacuum and the resulting solid was suspended into water (200 mL) and stirred overnight.
The solid was collected and dried to give the desire product as a brownish solid (8.05 g, 53.1percent yield).
1H NMR (500 MHz, CDCl3): δ2.21 (s, 3 H), 6.73 (d, J=8.1 Hz, 1 H), 6.94 (d, J=8.1 Hz, 1 H), 9.36 (brs, 1 H).
53.1% With bromine In pyridine; water a.
2-Bromo-3-hydroxy-6-methyl-pyridine
To a solution of 5-hydroxy-2-methylpyridine (8.80 g, 80.6 mmol) in 125 mL of pyridine was added a solution of bromine (14.18 g, 88.7 mmol) in 50 mL pyridine dropwise.
The temperature of the reaction mixture rose to 40° C. upon completion of addition.
After 1 hour the pyridine was removed under vacuum and the resulting solid was suspended into water (200 mL) and stirred overnight.
The solid was collected and dried to give the desire product as a brownish solid (8.05 g, 53.1percent yield).
1H NMR (500 MHz, CDCl3): δ2.21 (s, 3H), 6.73 (d, J=8.1 Hz, 1H), 6.94 (d, J=8.1 Hz, 1H), 9.36 (brs, 1H).
37% at 20℃; cooling with ice 2-methyl-5-hydroxypyridine (4.4 g, 40.3 mmol) was suspended in pyridine (85 mL) and cooled at ice-water. The bromine (7.1 g, 44.3 mmol) was slowly dropped into above cooled suspension. The ice-water bath was removed after finished bromine addition and the mixture was stirred overnight at room temperature. The pyridine was removed in vacuo. The residue was treated with water (100 mL) and stirred for 1 h. The solid product 48 (2.8 g, 37percent) was collected by filtration.
31.3% With bromine In pyridine; water (1)
Synthesis of 6-bromo-5-hydroxy-2-methylpyridine [R4=Br in Compound (XIV)]
To a solution obtained by dissolving 5-hydroxypicoline (10 g, 0.0916 mol) in pyridine (30 ml) was added dropwise bromine (15.4 g, 0.0916*1.05 mol), followed by stirring at room temperature for 4 hours.
Pyridine was then distilled off by an evaporator.
To the residue was added water and the precipitate was filtered out, washed with water to obtain a white solid.
Yield: 5.38 g, percent yield: 31.3percent, m.p.: 185-187° C. IR KBr cm-1: 2776, 1563, 1296, 1221, 1083, 831. 1H-NMR (60 MHz, d6-DMSO, δ): 2.26 (3H, s, CH3), 6.93 (1H, d, J=8 Hz, pyridine ring H), 7.1 (1H, d, J=8 Hz, pyridine ring H), 10.2 (1H, s OH).

Reference: [1] Tetrahedron Letters, 1995, vol. 36, # 30, p. 5319 - 5322
[2] Patent: WO2011/133659, 2011, A2, . Location in patent: Page/Page column 62-63
[3] Journal of Medicinal Chemistry, 2011, vol. 54, # 24, p. 8471 - 8489
[4] Tetrahedron, 2005, vol. 61, # 19, p. 4569 - 4576
[5] Patent: US2003/83357, 2003, A1,
[6] Patent: US6515003, 2003, B1,
[7] Helvetica Chimica Acta, 2009, vol. 92, # 11, p. 2238 - 2248
[8] Patent: US2012/316182, 2012, A1, . Location in patent: Page/Page column 93
[9] Patent: US6610853, 2003, B1,
[10] Journal of Organic Chemistry, 1996, vol. 61, # 14, p. 4623 - 4633
[11] Synlett, 2003, # 11, p. 1678 - 1682
[12] Synlett, 2003, # 11, p. 1678 - 1682
[13] Synlett, 2003, # 11, p. 1678 - 1682
[14] Synlett, 2003, # 11, p. 1678 - 1682
[15] Patent: US2003/55071, 2003, A1,
[16] Patent: US5266700, 1993, A,
[17] Patent: EP1935890, 2008, A1, . Location in patent: Page/Page column 43
[18] Patent: WO2012/123311, 2012, A1, . Location in patent: Page/Page column 43-44
[19] Patent: US2012/232061, 2012, A1, . Location in patent: Page/Page column 20-21
[20] Patent: WO2014/78690, 2014, A1, . Location in patent: Paragraph 00201
[21] Patent: WO2016/29214, 2016, A1, . Location in patent: Page/Page column 147-148
[22] Patent: EP3255042, 2017, A2, . Location in patent: Paragraph 0122; 0123
  • 4
  • [ 109-72-8 ]
  • [ 23003-29-4 ]
  • [ 91251-81-9 ]
  • [ 23003-35-2 ]
Reference: [1] Synlett, 2003, # 11, p. 1678 - 1682
  • 5
  • [ 1121-78-4 ]
  • [ 23003-29-4 ]
  • [ 23003-35-2 ]
Reference: [1] Synlett, 2003, # 11, p. 1678 - 1682
  • 6
  • [ 23003-29-4 ]
  • [ 594-19-4 ]
  • [ 23003-35-2 ]
  • [ 63688-35-7 ]
Reference: [1] Synlett, 2003, # 11, p. 1678 - 1682
  • 7
  • [ 23003-29-4 ]
  • [ 920-36-5 ]
  • [ 23003-35-2 ]
  • [ 14159-52-5 ]
Reference: [1] Synlett, 2003, # 11, p. 1678 - 1682
  • 8
  • [ 23003-35-2 ]
  • [ 170235-18-4 ]
Reference: [1] Journal of Organic Chemistry, 1996, vol. 61, # 14, p. 4623 - 4633
[2] Patent: WO2014/78690, 2014, A1,
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