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[ CAS No. 366-99-4 ] {[proInfo.proName]}

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3d Animation Molecule Structure of 366-99-4
Chemical Structure| 366-99-4
Chemical Structure| 366-99-4
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Product Details of [ 366-99-4 ]

CAS No. :366-99-4 MDL No. :MFCD00075040
Formula : C7H8FNO Boiling Point : -
Linear Structure Formula :- InChI Key :LJWAPDSCYTZUJU-UHFFFAOYSA-N
M.W : 141.14 Pubchem ID :581110
Synonyms :

Calculated chemistry of [ 366-99-4 ]

Physicochemical Properties

Num. heavy atoms : 10
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.14
Num. rotatable bonds : 1
Num. H-bond acceptors : 2.0
Num. H-bond donors : 1.0
Molar Refractivity : 37.3
TPSA : 35.25 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) : -6.22 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.57
Log Po/w (XLOGP3) : 1.32
Log Po/w (WLOGP) : 1.84
Log Po/w (MLOGP) : 1.58
Log Po/w (SILICOS-IT) : 1.53
Consensus Log Po/w : 1.57

Druglikeness

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

Water Solubility

Log S (ESOL) : -1.92
Solubility : 1.68 mg/ml ; 0.0119 mol/l
Class : Very soluble
Log S (Ali) : -1.66
Solubility : 3.08 mg/ml ; 0.0218 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -2.42
Solubility : 0.538 mg/ml ; 0.00381 mol/l
Class : Soluble

Medicinal Chemistry

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

Safety of [ 366-99-4 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302+H312+H332-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 366-99-4 ]

* 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 [ 366-99-4 ]
  • Downstream synthetic route of [ 366-99-4 ]

[ 366-99-4 ] Synthesis Path-Upstream   1~15

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Reference: [1] Journal of the American Chemical Society, 1959, vol. 81, p. 94,95, 97
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Reference: [1] Journal of the American Chemical Society, 1959, vol. 81, p. 94,95, 97
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Reference: [1] Journal of the American Chemical Society, 1959, vol. 81, p. 94,95, 97
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  • [ 399-96-2 ]
Reference: [1] Patent: US4861799, 1989, A,
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  • [ 363-47-3 ]
Reference: [1] Journal of Fluorine Chemistry, 2005, vol. 126, # 4, p. 661 - 667
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YieldReaction ConditionsOperation in experiment
98% With palladium on activated charcoal In ethyl acetate at 20℃; for 1 h; 3-Fluoro-4-methoxy-nitrobenzene (0.5 g, 2.9 mmol) was dissolved in ethyl acetate (10 mL) was added palladium on carbon (50 mg), stirred at room temperature for 1 hour. The reaction mixture was filtered, the filtrate was concentrated to give the title compound 3-fluoro-4-methoxyaniline (7B), an off-white solid (0.4 g, 98percent yield).
91% With hydrogen In ethanol at 20℃; for 4 h; To a mixture of 10percent Pd/C (1.5 grams) in ethanol (150 mL) taken in a Parr.(TM). hydrogenation flask was added a solution of 2-fluoro-4-nitroanisole (7) (9.09 grams, 53 mmol) in ethanol (150 mL) slowly.
The mixture was then stirred under hydrogen atmosphere (40 psi) for 4 hours at room temperature.
After completion of the reaction the mixture was filtered through Celite.(TM). and the residue was washed thoroughly using ethanol (20 mL).
The filtrates and washings were collected, combined and evaporated to dryness.
The solid obtained was stirred in hexane (50 mL) for 1 hour and filtered to give the desired product 3-fluoro-4-methoxyaniline (8) (6.75 grams).
78% With zinc In water at 20℃; for 0.0833333 h; Inert atmosphere General procedure: Under an argon atmosphere, a nitro group-containing compound (0.237 mmol) was weighed into a 5 mL microwave vial containing a magnetic stir bar and a Teflon-lined septum. Subsequently zinc dust (155 mg, 2.37 mmol), ammonium chloride (25 mg, 0.475 mmol) and the aqueous oligosaccharide solution (2 wt percent HPMC, 40-60 cps, in degassed Millipore water) were added and the reaction mixture was vigorously stirred at the indicated temperature for the indicated time. The reaction mixture was diluted with ethyl acetate, the solids were filtered and the aqueous phase was extracted 3x with ethyl acetate. The combined organic extracts were dried with magnesium sulfate, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel.; Following the general procedure using 2-fluoro-4-nitroanisole (171 mg, 1.00 mmol), zinc (327 mg, 5.00 mmol), ammonium chloride (64 mg, 1.20 mmol) and 2 ml of aqueous oligosaccharide solution (2 wt percent HPMC, 40-60 cps, in degassed Millipore water), the reaction was allowed to stir for 5 min at room temperature. After column chromatography (0-100 percent ethyl acetate - dichloromethane), the product was obtained (110 mg, 78 percent).ESI-MS: m/z (percent): 142.10 (100, [M+H]+).1H NMR (600MHz, d6-OMSO): δ [ppm] : 6.856.31 - 6.28 (m, 1H), 4.91 (sbr, 2H), 3.68 (s, 3H).
Reference: [1] Journal of Medicinal Chemistry, 2000, vol. 43, # 24, p. 4701 - 4710
[2] Patent: CN104395312, 2016, B, . Location in patent: Paragraph 0640-0645
[3] Patent: US2006/128729, 2006, A1, . Location in patent: Page/Page column 77
[4] Patent: WO2017/129796, 2017, A1, . Location in patent: Page/Page column 251; 252
[5] Journal of the American Chemical Society, 1941, vol. 63, p. 609
[6] Chemische Berichte, 1933, vol. 66, p. 1180,1183
[7] Journal of the American Chemical Society, 1940, vol. 62, p. 350,353
[8] Chemische Berichte, 1937, vol. 70, p. 2396,2400
[9] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1980, p. 832 - 834
[10] Patent: US4861799, 1989, A,
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Reference: [1] Journal of Medicinal Chemistry, 2000, vol. 43, # 24, p. 4701 - 4710
[2] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1980, p. 832 - 834
[3] Journal of the American Chemical Society, 1941, vol. 63, p. 609
[4] Chemische Berichte, 1933, vol. 66, p. 1180,1183
[5] Chemische Berichte, 1933, vol. 66, p. 1180,1183
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YieldReaction ConditionsOperation in experiment
21% With sodium hydroxide; sodium nitrite In hydrogenchloride; ethanol; water; ethyl acetate (i)
Ethyl 2-acetyl-2-N'-(3-chloro-methoxylphenyl)hydrazino)propionate
Ethereal HCl (60 ml) was added to a solution of 3-chloro-p-anisidine in ethyl acetate (300 ml) to precipitate the salt, which was isolated by filtration and air dried.
The salt (18.5 g) was suspended in 1.5 N HCl (230 ml) at -5° C. under argon.
A solution of sodium nitrite (6.9 g) in water (50 ml) was added over 15 minutes to form a solution/slurry, which was stirred at -5° C. for a further 1 hour. (solution A)
A solution of sodium hydroxide (5.36 g) in water (10 ml) was added to a solution of ethyl-2-methylacetoacetate (13.5 ml) in ethanol (80 ml) at 5° C.
The reaction was stirred at 5° C. for a further 1 hour and the pH was then adjusted to 4 by addition of sodium acetate (20 g).(solution B)
Solution B was added to solution A at -5° C. and the mixture was allowed to warm to ambient temperature over 3 hours before partitioning between water (250 ml) and ethylacetate (250 ml).
The organic phase was dried (MgSO4), concentrated under vacuo and purified by column chromatography using 15percent ethylacetate/isohexane as the eluant to yield the desired product (7 g, 21percent); NMR (CDCl3) δ 1.24 (t, 3H), 1.63 (s, 3H), 2.34 (s,3), 3.98 (s, 3H), 4.22-4.35 (m, 2H), 7.02 (d, 1H), 7.72 (dd, 1H), 7.83 (d, 1H) m/z 270(M-CH3COH)+
In a similar manner but starting from 3-fluoro-4-methoxyaniline was prepared:
Reference: [1] Patent: US2003/144339, 2003, A1,
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Reference: [1] Patent: US4431807, 1984, A,
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Reference: [1] Nature Chemistry, 2017, vol. 9, # 7, p. 681 - 688
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Reference: [1] Journal of Fluorine Chemistry, 2005, vol. 126, # 4, p. 661 - 667
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Reference: [1] Journal of Fluorine Chemistry, 2005, vol. 126, # 4, p. 661 - 667
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Reference: [1] Journal of the American Chemical Society, 1941, vol. 63, p. 609
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Reference: [1] Journal of the American Chemical Society, 1959, vol. 81, p. 94,95, 97
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Reference: [1] Synlett, 2012, vol. 23, # 8, p. 1205 - 1208
[2] Journal of the American Chemical Society, 1959, vol. 81, p. 94,95, 97
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