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Product Details of [ 1121-78-4 ]

CAS No. :1121-78-4 MDL No. :MFCD00006339
Formula : C6H7NO Boiling Point : -
Linear Structure Formula :HO(CH3)C5H3N InChI Key :DHLUJPLHLZJUBW-UHFFFAOYSA-N
M.W : 109.13 Pubchem ID :14275
Synonyms :

Calculated chemistry of [ 1121-78-4 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 8
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 : 31.23
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) : -6.39 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.19
Log Po/w (XLOGP3) : 0.81
Log Po/w (WLOGP) : 1.1
Log Po/w (MLOGP) : 0.13
Log Po/w (SILICOS-IT) : 1.38
Consensus Log Po/w : 0.92

Druglikeness

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

Water Solubility

Log S (ESOL) : -1.58
Solubility : 2.86 mg/ml ; 0.0262 mol/l
Class : Very soluble
Log S (Ali) : -1.09
Solubility : 8.93 mg/ml ; 0.0818 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -1.77
Solubility : 1.84 mg/ml ; 0.0169 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.09

Safety of [ 1121-78-4 ]

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 [ 1121-78-4 ]

* 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 [ 1121-78-4 ]
  • Downstream synthetic route of [ 1121-78-4 ]

[ 1121-78-4 ] Synthesis Path-Upstream   1~24

  • 1
  • [ 4134-97-8 ]
  • [ 56-40-6 ]
  • [ 1192-79-6 ]
  • [ 1121-78-4 ]
  • [ 1121-25-1 ]
Reference: [1] Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry, 1983, vol. 37, # 10, p. 879 - 890
  • 2
  • [ 4205-23-6 ]
  • [ 56-40-6 ]
  • [ 1192-79-6 ]
  • [ 1121-78-4 ]
  • [ 1121-25-1 ]
  • [ 1072-83-9 ]
Reference: [1] Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry, 1983, vol. 37, # 10, p. 879 - 890
  • 3
  • [ 4429-05-4 ]
  • [ 56-40-6 ]
  • [ 1192-79-6 ]
  • [ 1121-78-4 ]
  • [ 1121-25-1 ]
  • [ 1072-83-9 ]
Reference: [1] Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry, 1983, vol. 37, # 10, p. 879 - 890
  • 4
  • [ 1121-78-4 ]
  • [ 3430-13-5 ]
Reference: [1] Patent: EP1422218, 2004, A1, . Location in patent: Page 162
  • 5
  • [ 1121-78-4 ]
  • [ 36357-38-7 ]
Reference: [1] Patent: US2012/232281, 2012, A1,
[2] Patent: EP2497767, 2012, A1,
[3] RSC Advances, 2013, vol. 3, # 40, p. 18544 - 18549
  • 6
  • [ 1121-78-4 ]
  • [ 1122-43-6 ]
Reference: [1] Journal of the Chemical Society, 1957, p. 560,562
  • 7
  • [ 7732-18-5 ]
  • [ 57-50-1 ]
  • [ 1121-78-4 ]
  • [ 4664-12-4 ]
  • [ 40222-77-3 ]
  • [ 123-76-2 ]
Reference: [1] Nippon Nogei Kagaku Kaishi, 1940, vol. 16, p. 249,253, 264[2] Chem.Abstr., 1940, p. 6278,6940
[3] Bulletin of the Agricultural Chemical Society of Japan, 1939, vol. 15, p. 107
[4] Nippon Nogei Kagaku Kaishi, 1939, vol. 15, p. 629[5] Nippon Nogei Kagaku Kaishi, 1940, vol. 16, p. 253[6] Chem.Abstr., 1940, p. 432 6940
  • 8
  • [ 7732-18-5 ]
  • [ 1113-38-8 ]
  • [ 57-50-1 ]
  • [ 1121-78-4 ]
  • [ 4664-12-4 ]
  • [ 40222-77-3 ]
  • [ 123-76-2 ]
Reference: [1] Nippon Nogei Kagaku Kaishi, 1940, vol. 16, p. 249,253, 264[2] Chem.Abstr., 1940, p. 6278,6940
[3] Bulletin of the Agricultural Chemical Society of Japan, 1939, vol. 15, p. 107
[4] Nippon Nogei Kagaku Kaishi, 1939, vol. 15, p. 629[5] Nippon Nogei Kagaku Kaishi, 1940, vol. 16, p. 253[6] Chem.Abstr., 1940, p. 432 6940
  • 9
  • [ 1121-78-4 ]
  • [ 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,
  • 10
  • [ 1121-78-4 ]
  • [ 20348-16-7 ]
Reference: [1] Patent: US2008/138656, 2008, A1,
[2] Journal of Medicinal Chemistry, 1987, vol. 30, # 11, p. 2031 - 2046
[3] Patent: US4038396, 1977, A,
  • 11
  • [ 1121-78-4 ]
  • [ 15128-90-2 ]
YieldReaction ConditionsOperation in experiment
36.3% With nitric acid In conc. H2 SO4; ethyl acetate 117a.
3-Hydroxy-6-methyl-2-nitropyridine
5-Hydroxy-2-methylpyridine (23.6 g, 216 mmole)was dissolved in conc. H2 SO4 (50 mL) and cooled to 0° C. Fuming HNO3 (50 mL) was added over one hour.
The solution was stirred at room temperature for one hour, poured onto ice (400 g), and filtered.
The solids were dissolved in EtOAc washed with brine (100 mL).
The organic extracts were dried (MgSO4), and the solvent was evaporated to yield 12.1 g (36.3percent) of the title compound. mp 102-105° C. 1 H NMR (DMSO-d6, 300 MHz) δ: 2.44 (s, 3H), 7.52 (d, J=8.5 Hz, 1H), 7.58 (d J=8.5 Hz, 1H). MS (ESI -Q1MS) m/e 153(M-H)+. Anal. calcd. for C6 H6 N2 O3 C, 46.76 H, 3.92; N, 18.18 Found: C, 46.65 H, 3.98; N, 18.10.
Reference: [1] Heterocycles, 1994, vol. 38, # 3, p. 529 - 540
[2] Journal of Medicinal Chemistry, 1987, vol. 30, # 11, p. 2031 - 2046
[3] Patent: US6133253, 2000, A,
[4] Patent: US5155116, 1992, A,
[5] Patent: US5084456, 1992, A,
[6] Patent: US4038396, 1977, A,
  • 12
  • [ 1121-78-4 ]
  • [ 23003-30-7 ]
YieldReaction ConditionsOperation in experiment
50% With iodine; sodium hydroxide In water at 20℃; for 16 h; Step A:
6-Methylpyridin-3-ol (0.5 g, 4.58 mmol) was dissolved in aqueous NaOH (4.5 mL, 1 M, 4.5 mmol).
To the solution was added iodine (1.28 g, 5.2 mmol) and the mixture was stirred at room temperature overnight.
The mixture was neutralized with aqueous HCl (2 M) to pH ˜7.
A white precipitate formed and was collected by filtration.
The solid was washed with water and dried to give 2-iodo-6-methylpyridin-3-ol (0.8 g, 50percent). MS m/z 236.0 [M+H]+.
43.9%
Stage #1: With sodium carbonate In water at 20℃;
Stage #2: With iodine; potassium iodide In water for 0.583333 h;
Sodium carbonate (68.0 g) and water (810 mL) were added to 5-hydroxy-2-methylpyridine (1-014-01) (36.11 g), and the reaction mixture was stirred at room temperature, dissolved. To the reaction mixture was added dropwise a solution of iodine (117 g) and potassium iodide (117 g) in water (810 mL) for 35 min. The resulting pink-yellow crystal was filtered and dried under reduced pressure to give 2-iodo-3-hydroxy-6-methylpyridine (2-014-01) (34.1 g, 43.9percent, m.p. 187-190 °C)1H-NMR (300MHz, CDCl3+CD3OD): δ 2.45 (s,3H), 6.45 (d, J = 6.9 Hz, 1H), 7.02 (dd, J = 6.6, 1.5 Hz, 1H)
43.9% With iodine; sodium carbonate; potassium iodide In water at 20℃; for 0.583333 h; Sodium carbonate (68.0 g) and water (810 mL) were added to 5-hydroxy-2-methylpyridine (1-014-01) (36.11 g), and the reaction mixture was stirred at room temperature, dissolved. To the reaction mixture was added dropwise a solution of iodine (117 g) and potassium iodide (117 g) in water (810 mL) for 35 min. The resulting pink-yellow crystal was filtered and dried under reduced pressure to give 2-iodo-3-hydroxy-6-methylpyridine (2-014-01) (34.1 g, 43.9percent, m.p. 187-190 DEG C)<1>H-NMR (300MHz, CDCl3+CD3OD): delta 2.45 (s,3H), 6.45 (d, J= 6.9 Hz, 1H), 7.02 (dd, J= 6.6, 1.5 Hz, 1H)
8.19 g With iodine; sodium hydrogencarbonate In tetrahydrofuran; water at 20℃; for 72 h; To tetrahydrofuran / water (50 / 50mL) was added a mixed solution of pyridine-5 (6.458g, 60mmol), stirMix was added to the reaction flask followed by dissolution of iodine (16.8g, 66mmol), sodium bicarbonate (5.281g, 66mmol), at room temperature for 3 days, the reaction solution was dark purple solid separated, was added 10percent sodium thiosulfate solution purple to disappear, there are a lot of white solid precipitated was suction-white solid 8.19g, was verified by NMRThe product 6.

Reference: [1] Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 16, p. 2117 - 2122
[2] Patent: US9617268, 2017, B2, . Location in patent: Page/Page column 400; 401
[3] Patent: EP1477186, 2004, A1, . Location in patent: Page/Page column 35; 36
[4] Patent: EP1357111, 2003, A1, . Location in patent: Page/Page column 54
[5] Tetrahedron, 2007, vol. 63, # 13, p. 2787 - 2797
[6] Patent: US2011/230461, 2011, A1, . Location in patent: Page/Page column 32
[7] Patent: CN105693737, 2016, A, . Location in patent: Paragraph 0047; 0048
  • 13
  • [ 1121-78-4 ]
  • [ 24207-22-5 ]
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,
  • 14
  • [ 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
  • 15
  • [ 1121-78-4 ]
  • [ 23003-29-4 ]
  • [ 23003-35-2 ]
Reference: [1] Synlett, 2003, # 11, p. 1678 - 1682
  • 16
  • [ 1121-78-4 ]
  • [ 127978-70-5 ]
Reference: [1] Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 24, p. 6763 - 6770
[2] Tetrahedron Asymmetry, 2001, vol. 12, # 7, p. 1047 - 1054
[3] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 14, p. 3913 - 3924
[4] Patent: WO2007/120729, 2007, A2,
  • 17
  • [ 1121-78-4 ]
  • [ 22187-96-8 ]
Reference: [1] Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 24, p. 6763 - 6770
[2] Tetrahedron Asymmetry, 2001, vol. 12, # 7, p. 1047 - 1054
[3] Patent: WO2007/120729, 2007, A2,
  • 18
  • [ 1121-78-4 ]
  • [ 170235-18-4 ]
Reference: [1] Journal of Organic Chemistry, 1996, vol. 61, # 14, p. 4623 - 4633
[2] Patent: WO2014/78690, 2014, A1,
  • 19
  • [ 1121-78-4 ]
  • [ 221615-75-4 ]
Reference: [1] Patent: US2012/232281, 2012, A1,
[2] Patent: EP2497767, 2012, A1,
[3] RSC Advances, 2013, vol. 3, # 40, p. 18544 - 18549
[4] RSC Advances, 2013, vol. 3, # 40, p. 18544 - 18549
  • 20
  • [ 1121-78-4 ]
  • [ 659742-21-9 ]
Reference: [1] Patent: WO2005/32493, 2005, A2,
  • 21
  • [ 1121-78-4 ]
  • [ 383432-38-0 ]
Reference: [1] Organic Process Research and Development, 2007, vol. 11, # 3, p. 406 - 413
[2] Organic Process Research and Development, 2005, vol. 9, # 4, p. 440 - 450
[3] Organic Process Research and Development, 2005, vol. 9, # 4, p. 440 - 450
[4] Organic Process Research and Development, 2005, vol. 9, # 4, p. 440 - 450
[5] Organic Process Research and Development, 2005, vol. 9, # 4, p. 440 - 450
[6] Organic Process Research and Development, 2005, vol. 9, # 4, p. 440 - 450
[7] Organic Process Research and Development, 2005, vol. 9, # 4, p. 440 - 450
  • 22
  • [ 1121-78-4 ]
  • [ 380894-77-9 ]
Reference: [1] Patent: WO2011/162562, 2011, A2,
[2] ACS Medicinal Chemistry Letters, 2013, vol. 4, # 11, p. 1054 - 1058
[3] Journal of Medicinal Chemistry, 2017, vol. 60, # 16, p. 7166 - 7185
  • 23
  • [ 1121-78-4 ]
  • [ 713143-67-0 ]
Reference: [1] Patent: WO2011/162562, 2011, A2,
[2] ACS Medicinal Chemistry Letters, 2013, vol. 4, # 11, p. 1054 - 1058
[3] Journal of Medicinal Chemistry, 2017, vol. 60, # 16, p. 7166 - 7185
  • 24
  • [ 1121-78-4 ]
  • [ 615568-23-5 ]
Reference: [1] Patent: US2011/230461, 2011, A1,
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