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Product Details of [ 93-61-8 ]

CAS No. :93-61-8 MDL No. :MFCD00003283
Formula : C8H9NO Boiling Point : -
Linear Structure Formula :- InChI Key :JIKUXBYRTXDNIY-UHFFFAOYSA-N
M.W :135.16 Pubchem ID :66737
Synonyms :

Calculated chemistry of [ 93-61-8 ]

Physicochemical Properties

Num. heavy atoms : 10
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.12
Num. rotatable bonds : 2
Num. H-bond acceptors : 1.0
Num. H-bond donors : 0.0
Molar Refractivity : 41.24
TPSA : 20.31 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) : -6.35 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.73
Log Po/w (XLOGP3) : 1.09
Log Po/w (WLOGP) : 1.28
Log Po/w (MLOGP) : 1.93
Log Po/w (SILICOS-IT) : 1.08
Consensus Log Po/w : 1.42

Druglikeness

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

Water Solubility

Log S (ESOL) : -1.68
Solubility : 2.85 mg/ml ; 0.0211 mol/l
Class : Very soluble
Log S (Ali) : -1.11
Solubility : 10.5 mg/ml ; 0.0778 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -2.04
Solubility : 1.24 mg/ml ; 0.00918 mol/l
Class : Soluble

Medicinal Chemistry

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

Safety of [ 93-61-8 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P280 UN#:N/A
Hazard Statements:H302-H317 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 93-61-8 ]

* 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 [ 93-61-8 ]
  • Downstream synthetic route of [ 93-61-8 ]

[ 93-61-8 ] Synthesis Path-Upstream   1~44

  • 1
  • [ 554-14-3 ]
  • [ 93-61-8 ]
  • [ 13679-70-4 ]
Reference: [1] Journal of the Chemical Society, 1950, p. 2130,2134
[2] Journal of Organic Chemistry, 1949, vol. 14, p. 790,795
[3] Journal of the American Chemical Society, 1950, vol. 72, p. 1422
[4] Journal of Organic Chemistry, 1948, vol. 13, p. 635,637
  • 2
  • [ 96-43-5 ]
  • [ 93-61-8 ]
  • [ 7283-96-7 ]
Reference: [1] Journal of the American Chemical Society, 1950, vol. 72, p. 1422
[2] Journal of Organic Chemistry, 1948, vol. 13, p. 635,637
[3] Patent: US2741622, 1951, ,
[4] Journal of Organic Chemistry, 1949, vol. 14, p. 790,795
  • 3
  • [ 1003-09-4 ]
  • [ 93-61-8 ]
  • [ 4701-17-1 ]
Reference: [1] Journal of the American Chemical Society, 1950, vol. 72, p. 1422
[2] Journal of Organic Chemistry, 1949, vol. 14, p. 405,409
[3] Journal of Applied Spectroscopy, 2002, vol. 69, # 2, p. 230 - 237[4] Zhurnal Prikladnoi Spektroskopii, 2002, vol. 69, # 2, p. 200 - 206
  • 4
  • [ 638-02-8 ]
  • [ 93-61-8 ]
  • [ 26421-44-3 ]
Reference: [1] Journal of Organic Chemistry, 1949, vol. 14, p. 638,639
  • 5
  • [ 5780-36-9 ]
  • [ 93-61-8 ]
  • [ 24445-35-0 ]
Reference: [1] Monatsberichte der Deutschen Akademie der Wissenschaften zu Berlin, 1959, vol. 1, p. 180,181
  • 6
  • [ 93-61-8 ]
  • [ 95-15-8 ]
  • [ 24434-84-2 ]
  • [ 55219-11-9 ]
Reference: [1] Tetrahedron, 2012, vol. 68, # 24, p. 4588 - 4595
  • 7
  • [ 118-12-7 ]
  • [ 93-61-8 ]
  • [ 84-83-3 ]
Reference: [1] Patent: US2126852, 1934, ,
[2] Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 22, p. 336
[3] Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 25, p. 171
[4] Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 25, p. 171
  • 8
  • [ 479-59-4 ]
  • [ 93-61-8 ]
  • [ 33985-71-6 ]
Reference: [1] Journal of Organic Chemistry, 1952, vol. 17, p. 1281,1288
  • 9
  • [ 86-28-2 ]
  • [ 93-61-8 ]
  • [ 7570-45-8 ]
Reference: [1] Journal of Organic Chemistry, 1951, vol. 16, p. 1327,1330
  • 10
  • [ 86-28-2 ]
  • [ 93-61-8 ]
  • [ 7570-45-8 ]
  • [ 70207-46-4 ]
Reference: [1] Pharmazie, 1990, vol. 45, # 11, p. 863 - 863
  • 11
  • [ 16732-70-0 ]
  • [ 93-61-8 ]
  • [ 100123-25-9 ]
Reference: [1] Tetrahedron Letters, 2000, vol. 41, # 43, p. 8217 - 8220
[2] Farmaco, Edizione Scientifica, 1958, vol. 13, p. 113,114
  • 12
  • [ 39830-66-5 ]
  • [ 107-06-2 ]
  • [ 93-61-8 ]
  • [ 53462-88-7 ]
Reference: [1] Patent: US3950343, 1976, A,
[2] Patent: US3978066, 1976, A,
  • 13
  • [ 39830-66-5 ]
  • [ 93-61-8 ]
  • [ 53462-88-7 ]
Reference: [1] Patent: WO2008/110598, 2008, A1, . Location in patent: Page/Page column 30
  • 14
  • [ 75-44-5 ]
  • [ 75-77-4 ]
  • [ 18173-64-3 ]
  • [ 107-06-2 ]
  • [ 93-61-8 ]
  • [ 18162-48-6 ]
Reference: [1] Patent: US4780556, 1988, A,
  • 15
  • [ 93-61-8 ]
  • [ 120-21-8 ]
Reference: [1] Chemische Berichte, 1927, vol. 60, p. 121
  • 16
  • [ 51560-21-5 ]
  • [ 93-61-8 ]
  • [ 7310-97-6 ]
  • [ 90064-47-4 ]
Reference: [1] Journal of Medicinal Chemistry, 1984, vol. 27, # 8, p. 1071 - 1077
  • 17
  • [ 90064-46-3 ]
  • [ 93-61-8 ]
  • [ 90064-48-5 ]
  • [ 7310-97-6 ]
Reference: [1] Journal of Medicinal Chemistry, 1984, vol. 27, # 8, p. 1071 - 1077
  • 18
  • [ 634-36-6 ]
  • [ 93-61-8 ]
  • [ 2103-57-3 ]
Reference: [1] Journal of Organic Chemistry, 1954, vol. 19, p. 1548,1549
[2] Zhurnal Obshchei Khimii, 1959, vol. 29, p. 2900,2902; engl. Ausg. S. 2860, 2862
[3] Journal of the American Chemical Society, 1956, vol. 78, p. 1184,1186
  • 19
  • [ 251-41-2 ]
  • [ 93-61-8 ]
  • [ 31486-86-9 ]
Reference: [1] Heteroatom Chemistry, 2013, vol. 24, # 1, p. 25 - 35
  • 20
  • [ 6146-52-7 ]
  • [ 93-61-8 ]
  • [ 6625-96-3 ]
YieldReaction ConditionsOperation in experiment
80% With trichlorophosphate In ethyl acetate; 1,2-dichloro-ethane; benzene EXAMPLE 4
5-Nitro-3-indolealdehyde. [II, n=0, R2 =5-NO2, R3 =H]
A mixture of N-methylformanilide (176 mg, 1.3 mmol) and phosphorous oxychloride (199 mg, 1.3 mmol) is stirred for 15 min at 20°-25° C. under nitrogen. then a solution of 5-nitroindole (162 mg, 1 mmol) in 1,2-dichloroethane (5 ml) is added and the mixture heated to reflux for 3 h.
After cooling the mixture is poured onto iced water, the precipitate filtered off and washed with water.
Thereupon the residue is chromatographed over silica gel using benzene/ethyl acetate as eluant.
Thus pure title compound is obtained in 80percent yield (152 mg).
C9 H6 N2 O3 requires: C 56.85 H 3.18 N 14.73 found: C 56.79 H 3.01 N 14.51 MS m/z: 190 IR cm-1 (KBr): 3140, 3090 (NH), 1650 (CO), 1511, 1345 (NO2)
80% With trichlorophosphate In ethyl acetate; 1,2-dichloro-ethane; benzene EXAMPLE 6
5-nitro-3-indolealdehyde
A mixture of N-methylformanilide (1.76 g, 0.013 mol) and phosphorous oxychloride (1.99 g, 0.013 mol) was stirred for 15 min at 20°-25° C. under nitrogen.
Then a solution of 5-nitroindole (1.62 g, 0.01 mol) in 1,2-dichloroethane (50 ml) was added and the mixture heated to reflux for 3 h.
After cooling the mixture was poured onto iced water, the precipitate filtered off and washed with water.
Thereupon the residue was chromatographed over silica gel using benzene/ethylacetate as eluant.
Thus pure title compound was obtained in 80percent yield (1.52 g).
C9 H6 N2 O3 calculated: C 56.85 H 3.18 N 14.73 found: C 56.79 H,3.01 N 14.51
MS m/z 190.
IR cm-1: 3140, 3090 (NH), 1650 (CO), 1511, 1345 (NO2).
Reference: [1] Patent: US5409949, 1995, A,
[2] Patent: US5652250, 1997, A,
  • 21
  • [ 24599-58-4 ]
  • [ 93-61-8 ]
  • [ 4925-88-6 ]
YieldReaction ConditionsOperation in experiment
67%
Stage #1: at 20℃; for 0.666667 h;
Stage #2: at 50℃; for 6 h;
After stirring a mixture of 8.5 mi of N-methyifor maniiide (0.068 moi) and 6.3 mi of phosphorus oxytrichio ride (0.068 moi) at room temperature for 40 minutes, 17.8 g of 2,5-dimethoxytoiuene (0.117 moi) are introduced. The reaction mixture is heated for 6 hours at 500 C. and then, after returning to a temperature of 20 C., it is hydroiysed with 100 mi of aqueous 10percent sodium acetate soiution, extracted twice with diethyi ether and concentrated. The residue is taken up in aqueous sodium hydrogen suiphite soiution and extracted twice with diethyi ether. The aqueous phase is basied (pH=12) in order to give white crystais; m.p.=83 C.; yieid=67percent.
Reference: [1] Journal of Organic Chemistry, 2012, vol. 77, # 18, p. 8231 - 8243
[2] Patent: US2004/43995, 2004, A1, . Location in patent: Page 12
[3] Journal of Medicinal Chemistry, 1976, vol. 19, # 12, p. 1400 - 1404
[4] Patent: US2009/29976, 2009, A1, . Location in patent: Page/Page column 22
[5] Patent: US2004/19091, 2004, A1, . Location in patent: Page/Page column 6
  • 22
  • [ 24599-58-4 ]
  • [ 93-61-8 ]
  • [ 4925-88-6 ]
Reference: [1] Patent: US4034113, 1977, A,
  • 23
  • [ 129-00-0 ]
  • [ 93-61-8 ]
  • [ 3029-19-4 ]
Reference: [1] Chemistry - A European Journal, 2009, vol. 15, # 47, p. 12941 - 12944
[2] Chemistry - A European Journal, 2010, vol. 16, # 30, p. 9154 - 9163
[3] Justus Liebigs Annalen der Chemie, 1937, vol. 531, p. 1,35, 107
  • 24
  • [ 129-00-0 ]
  • [ 95-50-1 ]
  • [ 93-61-8 ]
  • [ 10025-87-3 ]
  • [ 3029-19-4 ]
Reference: [1] Justus Liebigs Annalen der Chemie, 1937, vol. 531, p. 1,35, 107
  • 25
  • [ 95-87-4 ]
  • [ 93-61-8 ]
  • [ 85231-15-8 ]
Reference: [1] Patent: US1807693, 1928, ,
[2] Patent: US1807693, 1928, ,
  • 26
  • [ 372-18-9 ]
  • [ 93-61-8 ]
  • [ 437-81-0 ]
YieldReaction ConditionsOperation in experiment
58% With n-butyllithium; sulfuric acid In tetrahydrofuran; hexane PREPARATION 14
2,6-Difluorobenzaldehyde
1,3-Difluorobenzene (25 g., 0.22 mole) was dissolved in 150 ml. of tetrahydrofuran and cooled to -50° C.
Butyl lithium (99 ml. of 2.3 M in hexane, 0.228 mole) was added over 20 minutes, maintaining the temperature at -50° C.
After 1.5 hours of stirring at the same temperature, N-methylformanilide (29.7 g., 0.22 mole) in 50 ml. of tetrahydrofuran was added over 20 minutes at -50° C.
After an additional 1.5 hours of stirring at -50° C., the reaction mixture was poured slowly into 1 liter of cold 1 N sulfuric acid, and extracted with three portions of ether.
The combined organic extracts were washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated to an oil.
The oil was distilled.
Middle cuts were combined to yield 2,6-difluorobenzaldehyde (18.2 g., 58percent; b.p. 72°-74°/12 mm.).
Reference: [1] Patent: US4367234, 1983, A,
[2] Journal of Medicinal Chemistry, 1968, vol. 11, # 4, p. 814 - 819
  • 27
  • [ 50638-47-6 ]
  • [ 93-61-8 ]
  • [ 4903-09-7 ]
Reference: [1] Bulletin of the Chemical Society of Japan, 2006, vol. 79, # 7, p. 1091 - 1099
  • 28
  • [ 621-23-8 ]
  • [ 93-61-8 ]
  • [ 830-79-5 ]
Reference: [1] Journal of Medicinal Chemistry, 2005, vol. 48, # 7, p. 2407 - 2419
  • 29
  • [ 608-25-3 ]
  • [ 93-61-8 ]
  • [ 6248-20-0 ]
YieldReaction ConditionsOperation in experiment
57% With trichlorophosphate In water; acetone A.
Preparation of 2,4-Dihydroxy-3-methylbenzaldehyde
Phosphorus oxychloride (80 mL, 0.86 mol) was added to a stirred mixture of N-methylformanilide (102 mL, 0.82 mol) in ether (250 mL).
The mixture was stirred for 1 hour at room temperature and then cooled in ice. 2-Methyl resorcinol (Aldrich, 100 g, 0.81 mol) was added and the mixture was allowed to warm to room temperature while stirring overnight.
The precipitated intermediate product was collected by filtration and rinsed with ether (3x).
The intermediate was hydrolyzed by dissolving in a mixture of acetone (250 mL) and water (250 mL) and stirring for 30 minutes.
Water (2 L) was added, the mixture was brought to a boil, and then allowed to cool and deposit crystalline product.
This was recrystallized a second time from water (4 L) to afford pure product (70 g, 57percent). M.p. 150° C. (Lit. 152-3° C. [W. Baker et al., J. Chem. Soc., 2834-5 (1949).]. NMR (DMSO-d6): w 1.973 (s, 3H), 6.551 (d, J=8.5 hz, 1H), 7.428 (d, J-8.5 hz, 1H), 9.703 (s,
1H), 10.745 (s, 1H), and 11.592 (s, 1H).
57% With trichlorophosphate In water; acetone A.
Preparation of 2,4-Dihydroxy-3-methylbenzaldehyde
Phosphorus oxychloride (80 mL, 0.86 mol) was added to a stirred mixture of N-methylformanilide (102 mL, 0.82 mol) in ether (250 mL).
The mixture was stirred for 1 hour at room temperature and then cooled in ice. 2-Methyl resorcinol (Aldrich, 100 g 0.81 mol) was added and the mixture was allowed to warm to room temperature while stirring overnight.
The precipitated intermediate product was collected by filtration and rinsed with ether (3*).
The intermediate was hydrolyzed by dissolving in a mixture of acetone (250 mL) and water (250 mL) and stirring for 30 minutes.
Water (2 L) was added, the mixture was brought to a boil, and then allowed to cool and deposit crystalline product.
This was recrystallized a second time from water (4 L) to afford pure product (70 g, 57percent). M.p. 150° C. (Lit. 152°-3° C. [W. Baker et al., J. Chem. Soc., 2834-5 (1949).]. NMR (DMSO-d6): δ 1.973 (s, 3H), 6.551 (d, J=8.5 hz, 1H), 7.428 (d, J-8.5 hz, 1H), 9.703 (s, 1H), 10.745 (s, 1H), and 11.592 (s, 1H),
57% With trichlorophosphate In water; acetone A.
Preparation of 2,4-Dihydroxy-3-methylbenzaldehyde
Phosphorus oxychloride (80 mL, 0.86 mol) was added to a stirred mixture of N-methylformanilide (102 mL, 0.82 mol) in ether (250 mL).
The mixture was stirred for 1 hour at room temperature and then cooled in ice. 2-Methyl resorcinol (Aldrich, 100 g, 0.81 mol) was added and the mixture was allowed to warm to room temperature while stirring overnight.
The precipitated intermediate product was collected by filtration and rinsed with ether (3*).
The intermediate was hydrolyzed by dissolving in a mixture of acetone (250 mL) and water (250 mL) and stirring for 30 minutes.
Water (2 L) was added, the mixture was brought to a boil, and then allowed to cool and deposit crystalline product.
This was recrystallized a second time from water (4 L) to afford pure product (70 g, 57percent). M.p. 150° C. (Lit. 152°-3° C. [W. Baker et al., J. Chem. Soc., 2834-5 (1949).]. NMR (DMSO-d6): δ1.973 (s, 3H), 6.551 (d, J=8.5 hz, 1H), 7.428 (d, J=8.5 hz, 1H), 9.703 (s, 1H), 10.745 (s, 1H), and 11.592 (s, 1H).
Reference: [1] Patent: US5151507, 1992, A,
[2] Patent: US5047519, 1991, A,
[3] Patent: US5102785, 1992, A,
  • 30
  • [ 1199-08-2 ]
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  • [ 50505-61-8 ]
Reference: [1] Journal of Medicinal Chemistry, 1974, vol. 17, p. 1100 - 1111
[2] Journal of Medicinal Chemistry, 1975, vol. 18, # 12, p. 1201 - 1204
  • 31
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  • [ 2216-69-5 ]
  • [ 15971-29-6 ]
Reference: [1] Tetrahedron, 1975, vol. 31, p. 1005 - 1009
  • 32
  • [ 38843-85-5 ]
  • [ 93-61-8 ]
  • [ 53581-81-0 ]
Reference: [1] Journal of Medicinal Chemistry, 1974, vol. 17, p. 1100 - 1111
[2] Journal of Medicinal Chemistry, 1975, vol. 18, # 12, p. 1201 - 1204
  • 33
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  • [ 93-61-8 ]
  • [ 94-31-5 ]
Reference: [1] Patent: US2001/3649, 2001, A1,
  • 34
  • [ 1669-85-8 ]
  • [ 93-61-8 ]
  • [ 94-31-5 ]
Reference: [1] DRP/DRBP Org.Chem.,
[2] Journal of the Chemical Society, 1944, p. 489,491
[3] Patent: US2141090, 1936, ,
  • 35
  • [ 62351-47-7 ]
  • [ 93-61-8 ]
  • [ 32085-88-4 ]
Reference: [1] Patent: US4424229, 1984, A,
  • 36
  • [ 540-36-3 ]
  • [ 93-61-8 ]
  • [ 2646-90-4 ]
YieldReaction ConditionsOperation in experiment
77.5% With n-butyllithium In tetrahydrofuran; hexane EXAMPLE 3
2,5-Difluorobenzaldehyde
To a stirred solution of 194.5 g (1.70 mol) of 1,4-difluorobenzene in 2 of dry tetrahydrofuran at -60° C. was added dropwise over 45 mins 1.70 mol (2.2M in hexane) of n-butyllithium at a rate such that the temperature remained below -55° C.
The reaction mixture was stirred for 45 mins at below -50° C. and 1.5 hr at -50° to -45° C.
The solution was then cooled to -60° C. and a solution of 230 g of N-methylformanilide in 300 ml of tetrahydrofuran was added dropwise over 30 mins.
The mixture was stirred for 1 hr at -50° C. and allowed to warm to -30° C. over 15 mins.
The mixture was then poured into ice water, neutralized (pH 6-7) with 10percent sulfuric acid and extracted three times with hexane.
The extracts were washed once with 1N sulfuric acid, once with saturated sodium chloride solution and concentrated to an oil.
Distillation at 64°-65° C. (20 mm) provided 187.5 g (77.5percent) of product.
Reference: [1] Patent: US4654336, 1987, A,
  • 37
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  • [ 360575-28-6 ]
YieldReaction ConditionsOperation in experiment
100%
Stage #1: With hydrogenchloride; n-butyllithium; diisopropylamine In tetrahydrofuran; hexanes at -78 - -70℃; for 2.5 h;
Stage #2: at -78 - -70℃; for 2 h;
PREPARATION 6
1-Bromo-3-fluorobenzaldehyde
To a solution of diisopropylamine (2.27 mol, 320 mL) in anhydrous tetrahydrofuran (800 mL) in a 5 L flask at 0° C. add 1.6 M butyllithium (1.16 L, 1.86 mol) in hexanes dropwise over 1.5 h.
Stir the resulting yellow solution at 0° C. for 30 min.
In a separate 12 L flask dissolve 1-bromo-3-fluorobenzene (203 mL, 1.86 mol) in anhydrous tetrahydrofuran (650 mL) and cool to -78° C.
Transfer the preformed LDA solution to an addition funnel via cannula and add dropwise to the 1-bromo-3-fluorobenzene solution over 2 h so the temperature does not rise above -70° C.
Stir the resulting slurry at -78° C. for 30 min.
Add a solution of N-methyl-N-phenyl formamide (230 mL, 1.86 moles, 1.00 equiv.) in anhydrous tetrahydrofuran (1.15 L) dropwise at -78° C. over one hour while maintaining the temperature below -70° C.
Stir the reaction cold for 2 h while slowly allowing it to rise to room temperature overnight.
Dilute the reaction with methyl tert-butyl ether (3 L), quench with 1M hydrochloric acid (4 L) and stir vigorously for 3 h.
Separate the layers and extract the aqueous layer with methyl tert-butyl ether (1 L).
Wash the combined organic phases with 1M hydrochloric acid (2*1 L), water (1 L), brine (1 L), dry over magnesium sulfate, filter and concentrate to an orange oil that slowly solidifies to obtain the title compound (394 g, 105percent).
1H NMR (CDCl3) δ 10.37 (s, 1H), 7.50 (d, 1H), 7.44 (m, 1H), 7.17 (t, 1H).
Reference: [1] Patent: US2009/163472, 2009, A1, . Location in patent: Page/Page column 18
  • 38
  • [ 93-61-8 ]
  • [ 150-78-7 ]
  • [ 5312-97-0 ]
YieldReaction ConditionsOperation in experiment
71%
Stage #1: at 0℃; for 0.5 h;
Stage #2: at 100℃; for 10 h;
Stage #3: With ammonia; iodine In tetrahydrofuran; water; N,N-dimethyl-formamide at 20℃; for 3 h;
General procedure: To an ice cooled solution of N-methylformanilide (2.2 mmol) was added dropwise diphosphoryl chloride (2.2 mmol). The solution was stirred for 30 min at 0 °C, and then 1,2-dimethoxybenzene (276.3 mg, 2 mmol) in DMF (1.0 mL) was added dropwise. After being stirred for 10 h at 100 °C, I2 (1015.2 mg, 4 mmol), aq NH3 (4 mL, 28-30percent) and THF (1 mL) were added to the reaction mixture. The obtained mixture was stirred for 3 h at rt. After the reaction, the mixture was poured into aq satd Na2SO3 solution and extracted with CHCl3 (3.x.20 mL). The organic layer was dried over Na2SO4, filtered, and evaporated. The product was purified by flash short column chromatography (Hexane:AcOEt=3:1) to afford 3,4-dimethoxybenzonitrile as a white solid in 92percent yield.
Reference: [1] Tetrahedron, 2012, vol. 68, # 24, p. 4588 - 4595
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  • [ 90064-48-5 ]
  • [ 7310-97-6 ]
Reference: [1] Journal of Medicinal Chemistry, 1984, vol. 27, # 8, p. 1071 - 1077
  • 40
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  • [ 93957-49-4 ]
  • [ 93-61-8 ]
  • [ 93957-50-7 ]
YieldReaction ConditionsOperation in experiment
70% With bis(trichloromethyl) carbonate; trichlorophosphate In chlorobenzene at 5 - 80℃; Example 6 3-[3-(4-Fluorophenyl)-1-(1-Methylethyl)-1H-Indol-2-yl]-2-Propenal The product is synthesised as described in Example 5 using chlorobenzene as solvent (70percent yield).
69% With bis(trichloromethyl) carbonate; trichlorophosphate In acetonitrile at 5 - 80℃; Example 5
3-[3-(4-Fluorophenyl)-1-(1-Methylethyl)-1H-Indol-2-yl]-2-Propenal
To a solution of N-methylformanilide (30 g), butyl vinyl ether (22.2 g) in 15 ml of acetonitrile under stirring at 5°C, a solution of bis-trichloromethylcarbonate (26.1 g) in 70 ml of acetonitrile is added dropwise in 80 min.
The reaction mixture is kept under stirring at 5°C overnight, then phosphorus oxychloride (31.4 g) is added dropwise in 30 minutes, then the reaction mixture is stirred at 5°C for 15 minutes. 3-[3-(4-Fluorophenyl)-1-(1-Methylethyl)-1H-Indole (35.8 g) and acetonitrile (25 ml) are added.
The mixture is warmed to 80°C and kept under stirring for about 24 hours.
The reaction mixture is worked up as described in Example 3b to give the product (69percent yield).
Reference: [1] Patent: EP1477474, 2004, A1, . Location in patent: Page column 6
[2] Patent: EP1477474, 2004, A1, . Location in patent: Page column 6
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  • [ 93957-49-4 ]
  • [ 109-92-2 ]
  • [ 93-61-8 ]
  • [ 93957-50-7 ]
Reference: [1] Journal of Organic Chemistry, 1992, vol. 57, # 11, p. 3250 - 3252
  • 42
  • [ 93-61-8 ]
  • [ 204905-77-1 ]
Reference: [1] Chemical Communications, 2005, # 33, p. 4187 - 4189
  • 43
  • [ 392-85-8 ]
  • [ 93-61-8 ]
  • [ 112641-20-0 ]
Reference: [1] Patent: EP225175, 1988, A3,
  • 44
  • [ 102-54-5 ]
  • [ 93-61-8 ]
  • [ 12093-10-6 ]
  • [ 1271-48-3 ]
Reference: [1] Chemistry and Industry (London, United Kingdom), [2] Chemistry and Industry (London, United Kingdom), 1957, p. 72 - 72
[3] , Gmelin Handbook: Fe: Org.Verb.A1, 2.5.7.7, page 161 - 162,
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