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Product Details of [ 603-76-9 ]

CAS No. :603-76-9 MDL No. :MFCD00005800
Formula : C9H9N Boiling Point : -
Linear Structure Formula :- InChI Key :BLRHMMGNCXNXJL-UHFFFAOYSA-N
M.W : 131.17 Pubchem ID :11781
Synonyms :
Chemical Name :1-Methyl-1H-indole

Calculated chemistry of [ 603-76-9 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 10
Num. arom. heavy atoms : 9
Fraction Csp3 : 0.11
Num. rotatable bonds : 0
Num. H-bond acceptors : 0.0
Num. H-bond donors : 0.0
Molar Refractivity : 43.2
TPSA : 4.93 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) : -5.17 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.94
Log Po/w (XLOGP3) : 2.72
Log Po/w (WLOGP) : 2.18
Log Po/w (MLOGP) : 1.89
Log Po/w (SILICOS-IT) : 2.01
Consensus Log Po/w : 2.15

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 2.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -3.03
Solubility : 0.122 mg/ml ; 0.000927 mol/l
Class : Soluble
Log S (Ali) : -2.48
Solubility : 0.437 mg/ml ; 0.00333 mol/l
Class : Soluble
Log S (SILICOS-IT) : -2.81
Solubility : 0.204 mg/ml ; 0.00156 mol/l
Class : Soluble

Medicinal Chemistry

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

Safety of [ 603-76-9 ]

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 [ 603-76-9 ]

* 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 [ 603-76-9 ]
  • Downstream synthetic route of [ 603-76-9 ]

[ 603-76-9 ] Synthesis Path-Upstream   1~27

  • 1
  • [ 603-76-9 ]
  • [ 124-38-9 ]
  • [ 16136-58-6 ]
Reference: [1] Angewandte Chemie - International Edition, 2014, vol. 53, # 32, p. 8416 - 8420[2] Angew. Chem., 2014, vol. 126, # 32, p. 8556 - 8560,5
  • 2
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  • [ 16136-58-6 ]
Reference: [1] Journal of the American Chemical Society, 1953, vol. 75, p. 375,377
  • 3
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  • [ 124-38-9 ]
  • [ 32387-21-6 ]
  • [ 16136-58-6 ]
Reference: [1] Chemical Communications, 2014, vol. 50, # 92, p. 14360 - 14363
  • 4
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  • [ 109-72-8 ]
  • [ 60-29-7 ]
  • [ 124-38-9 ]
  • [ 16136-58-6 ]
Reference: [1] Journal of the American Chemical Society, 1953, vol. 75, p. 375,377
  • 5
  • [ 25055-55-4 ]
  • [ 603-76-9 ]
  • [ 10075-52-2 ]
  • [ 1198788-42-9 ]
  • [ 81471-20-7 ]
Reference: [1] European Journal of Organic Chemistry, 2014, vol. 2014, # 18, p. 3802 - 3807
  • 6
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  • [ 10075-52-2 ]
  • [ 1198788-42-9 ]
  • [ 81471-20-7 ]
Reference: [1] European Journal of Organic Chemistry, 2014, vol. 2014, # 18, p. 3802 - 3807
  • 7
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  • [ 61-70-1 ]
YieldReaction ConditionsOperation in experiment
90% With 1-fluoro-1,2-phenyliodohydrin-3-(1H)-one In 1,4-dioxane; water at 140℃; for 5 h; 0.4 mL of 1,4-dioxane was added to a 50 mL reaction tube at room temperature.Add 2mL of water,Stir and mix,Weighing 1-fluoro-1,2-phenyliodohydrin-3-(1H)-one (175 mg, 0.66 mmol) was added to the reaction tube and stirred for 1 min.After the reaction tube was placed in a 140 ° C oil bath,Was added N- methylindole (78mg, 0.6mmol),And with a built-in condenser, react in a 140 ° C oil bath for 5 hours.The TLC dot plate showed complete reaction of the starting material.Take the reaction tube out of the oil bath and cool to room temperature.The reaction was quenched by the addition of 10 mL of saturated sodium bicarbonate.Extracted with 20 mL of ethyl acetate.The organic layer was combined, dried over anhydrous sodium sulfate and evaporated.The yellow solid N-methyl-2-indanone 79 mg was obtained by column chromatography to give a yield of 90percent.
Reference: [1] European Journal of Organic Chemistry, 2018, vol. 2018, # 12, p. 1437 - 1442
[2] Patent: CN108129377, 2018, A, . Location in patent: Paragraph 0016-0017; 0019; 0021; 0023; 0025; 0027; 0029
[3] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1990, # 4, p. 597 - 603
[4] Journal of the American Chemical Society, 2017, vol. 139, # 34, p. 11887 - 11894
  • 8
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  • [ 61-70-1 ]
  • [ 1414867-74-5 ]
  • [ 1414867-88-1 ]
Reference: [1] Organic Letters, 2012, vol. 14, # 23, p. 5832 - 5835
  • 9
  • [ 288-13-1 ]
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  • [ 61-70-1 ]
  • [ 1414867-74-5 ]
Reference: [1] Organic Letters, 2012, vol. 14, # 23, p. 5832 - 5835
  • 10
  • [ 603-76-9 ]
  • [ 934-16-7 ]
  • [ 61-70-1 ]
  • [ 5585-14-8 ]
  • [ 82414-24-2 ]
  • [ 82414-19-5 ]
Reference: [1] Tetrahedron, 1982, vol. 38, # 1, p. 173 - 182
  • 11
  • [ 603-76-9 ]
  • [ 61-70-1 ]
  • [ 128590-00-1 ]
Reference: [1] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1990, # 4, p. 597 - 603
[2] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1990, # 4, p. 597 - 603
  • 12
  • [ 94493-20-6 ]
  • [ 603-76-9 ]
  • [ 1006-94-6 ]
  • [ 61-70-1 ]
  • [ 2521-13-3 ]
Reference: [1] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1984, # 8, p. 1331 - 1340
  • 13
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  • [ 36728-89-9 ]
Reference: [1] Heterocycles, 2006, vol. 70, p. 51 - 56
[2] Organic Letters, 2017, vol. 19, # 9, p. 2266 - 2269
  • 14
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  • [ 36728-89-9 ]
  • [ 99459-48-0 ]
Reference: [1] Synthesis, 1999, # 7, p. 1117 - 1122
[2] Synthesis, 1999, # 7, p. 1117 - 1122
  • 15
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  • [ 29055-08-1 ]
Reference: [1] European Journal of Organic Chemistry, 2017, vol. 2017, # 45, p. 6652 - 6659
  • 16
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  • [ 75833-63-5 ]
YieldReaction ConditionsOperation in experiment
20%
Stage #1: With n-butyllithium In diethyl ether; hexane at 0℃; for 3.5 h; Reflux
Stage #2: With iodine In diethyl ether; hexane at 15℃; for 1 h;
To a solution of N-methylindole (7.00 g, 53.40 mmol) in Et2O (160 mL) at 0 °C was added nBuLi (30mL, 2.67 M in hexane, 80.10 mmol). The solution was stirred for 0.5 h at 0 °C and heated at reflux for 3h. After cooling to 15 °C, iodine (14.90 g, 58.70 mmol) was added and stirred for 1h at 15 °C. Thereaction was quenched with 20percent aq. Na2S2O3 (50 mL) and AcOEt (50 mL) was added, the layers wereseparated, and the aqueous layer was extracted with AcOEt (50 mL). The organic layers were combined,washed successively with sat. aq. NaHCO3 (50 mL), H2O (50 mL), dried over MgSO4, and concentratedin vacuo. The residue was purified by recrystallization from petroleum ether (20 mL) to afford 2a (5.78g,42percent yield) as a light brown crystal. The filtrate was concentrated in vacuo, the residue was purified byflash chromatography (silica gel, hexane/AcOEt = 70:1), and then by recrystallization from hexane (15mL) to afford 2a (2.74g, 20percent yield) as a white crystal.
Reference: [1] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1982, vol. 31, # 11, p. 2226 - 2229[2] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1982, # 11, p. 2524 - 2527
[3] Angewandte Chemie - International Edition, 2006, vol. 45, # 14, p. 2274 - 2277
[4] Chemistry - A European Journal, 2018, vol. 24, # 15, p. 3725 - 3728
[5] Tetrahedron, 2013, vol. 69, # 45, p. 9481 - 9493
[6] Tetrahedron, 1980, vol. 36, # 10, p. 1439 - 1443
[7] Chemistry - A European Journal, 2010, vol. 16, # 5, p. 1670 - 1678
  • 17
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  • [ 1189-71-5 ]
  • [ 118959-44-7 ]
Reference: [1] Tetrahedron, 1989, vol. 45, # 20, p. 6427 - 6438
[2] Journal of Medicinal Chemistry, 2013, vol. 56, # 17, p. 7060 - 7072
[3] Current Medicinal Chemistry, 2014, vol. 21, # 14, p. 1654 - 1666
  • 18
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  • [ 118959-44-7 ]
Reference: [1] Marine Drugs, 2016, vol. 14, # 12,
  • 19
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  • [ 118959-44-7 ]
Reference: [1] Synthesis, 2003, # 16, p. 2525 - 2529
[2] Marine Drugs, 2015, vol. 13, # 1, p. 460 - 492
  • 20
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  • [ 215734-58-0 ]
  • [ 78581-99-4 ]
  • [ 27065-95-8 ]
YieldReaction ConditionsOperation in experiment
12% at 110℃; for 35 h; Compound 1 (0.225 g, 1.35 mmol) was heated with1-methylindole (0.5 g, 3.8 mmol) in AcOH (3 mL) at 110°C for 35 h, cooled, and stored at 20–25 for 12 h. The resultingprecipitate was filtered off and recrystallized from DMF. Yield of tris(1-methylindol-3-yl)methane (4a), 0.060 g (12percent),mp 241–243°C [6]. The PMR spectrum was published [6]. Mass spectrum (EI, 70 eV), m/z (Irel, percent): 404 (29), 403 (M+, 100),402 (44), 272 (75), 271 (85), 257 (15).
Reference: [1] Chemistry of Natural Compounds, 2017, vol. 53, # 3, p. 519 - 522[2] Khim. Prir. Soedin., 2017, # 3, p. 441 - 443,3
  • 21
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  • [ 76-09-5 ]
  • [ 274-07-7 ]
  • [ 837392-62-8 ]
  • [ 683229-61-0 ]
YieldReaction ConditionsOperation in experiment
67 %Spectr.
Stage #1: With thiophene; tris(pentafluorophenyl)borate In 1,2-dichloro-ethane at 80℃; for 40 h; Schlenk technique; Inert atmosphere
Stage #2: With triethylamine In 1,2-dichloro-ethane at 20℃; Schlenk technique; Inert atmosphere
General procedure: In a 20 mL Schlenk tube under Ar, B(C6F5)3 (51.2 mg, 0.10 mmol) was dissolved in distilled1,2-dichloroethane (2 mL), followed by the addition of catecholborane (2, 117 μL, 1.1 mmol) andtetrahydrothiophene (9 μL, 0.10 mmol). Then, to the mixture was added the arene substrate (1.0mmol), and the resulting mixture was heated to 80 °C (oil bath temp.) and stirred for the appropriatereaction time. After cooling to room temperature, excess Et3N (2 mL, ca. 15 mmol) and then, pinacol(355 mg, 3 mmol) were added to the reaction mixture and stirred. The reaction mixture wasquenched by aqueous NH4Cl, extracted with EtOAc, washed with brine, and dried over Na2SO4.Purification by silica gel column chromatography (eluent: CH2Cl2/hexane) was performed to affordthe borylated products.
Reference: [1] Heterocycles, 2017, vol. 95, # 1, p. 158 - 166
  • 22
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  • [ 1032452-86-0 ]
YieldReaction ConditionsOperation in experiment
92%
Stage #1: With graphene supported FeCl3 In ethanol; butanone at 30 - 40℃; for 0.333333 h;
Stage #2: at 15 - 50℃; for 6 h;
1) 100 g of 2,4-dichloropyrimidine,(^ The graphene-supported? Lean catalyst prepared in Example 1 was placed in ethanol and methyl ethyl ketoneOf the mixed solution (500 ml, the volume ratio of ethanol to methyl ethyl ketone was 4: 1)In the 30-40 ° C stirring 20min;2) the temperature of the reaction system to 15 ° C, and then by adding 1-methyl-1H-indole, control the process of adding the reaction system temperature does not exceed 15 ° C;3) After 1-methyl-1H-indole was added dropwise, the temperature was raised to 30 ° C at a heating rate of 5 ° C / h and the incubation was carried out at 30 ° C for 3 h; then the temperature was raised to 5 ° C / h 40 ° C, 40 ° C insulation reaction 2h; the final 5 ° C / h heating rate to 50 ° C, 50 ° C insulation reaction lh;4) the end of the incubation reaction, cooling to room temperature, 0.5 micron microfiltration filter to remove the graphene-loaded FeCl3 catalyst, the filtrate at 40 ° C under reduced pressure to dry, and then add 600ml n-heptane to the system in 35- 40 ° C under the beating 6-8h, after the end of the filter,Dried to give 3- (2-chloropyrimidin-4-yl) -1-methylindole (yield 92percent, HPLC area normalized purity 99.3percent).
85%
Stage #1: With iron(III) chloride In Dimethyl ether at 10 - 35℃;
Stage #2: at 50℃;
Intermediate 7: 3-(2-chloropyrimidin-4-yl)-1-methylindole
To a 1 L three-neck flask, were added 40 g 2,4-dichloropyrimidine and 200 mL DME, after dissolved, cooled to 10 to 15°C, 45 g anhydrous FeCl3 was added in portions rapidly, the temperature was kept at or below 35°C, and the mixture was stirred for 15 min after each portion was added.
52.8 g 1-methylindole was added dropwise into the above reaction system, then the mixture was heated slowly to 50°C, stirred overnight, the reaction was monitored by TLC until it finished.
The reaction mixture was cooled to 5 to 10°C, about 300 mL methanol aqueous solution (1:2, v/v) was slowly added dropwise and large amount of viscous solid was precipitated.
The mixture was filtered, the filter cake was washed with methanol twice, after filtration, dried under reduced pressure at 50°C, yield 85percent.
81.5% With iron(III) chloride In 1,2-dimethoxyethane at 60℃; To a stirred solution 2,4-dichloropyrimidine (70.5 g, 463.76 mmol) in dimethoxyethane (900 mL) was added FeCl3 (77.16 g, 459.12 mmol) and 1-methyl indole (68.28 g) at 60°C. The resulting mixture was stirred overnight at 60°C. After cooling, a solid was precipitated by adding methanol (345 mL) and water (900 mL). The resulting slurry was stirred for 3h. The solid was collected by filtration, washed with CH3OH (1.38 L) and dried at 50°C overnight to give the title compound (138.7 g, 81.5percent) as a purple solid; 1H NMR (CDCl3) 3.89 (3H, s), 7.36-7.41 (3H, m), 7.49 (1H, s), 7.96 (1H, s), 8.34 (1H, s), 8.45 (1H, s); m/z: ES+ MH+ 244.05.
72% With aluminum (III) chloride In 1,2-dimethoxyethane at 60℃; for 3 h; Inert atmosphere N-methylindole (300 mg, 2.29 mmol), 2,4-dichloropyrimidine (340 mg, 2.30 mmol) and anhydrous aluminum trichloride (460 mg, 3.43 mmol) were dissolved in ethylene glycol dimethyl ether (12 mL). The reaction was heated to 60 °C in a nitrogen atmosphere and stirred for 3 hours. After the reaction was completed, the reaction solution was poured into an ice-water mixture (about 50 mL) and extracted with methyl tert-butyl ether (20 mL*3). The organic phases were combined, dried over anhydrous magnesium sulfate, filtered and concentrated. The resulting residue was purified by column chromatography to obtain the product 3-(2-chloropyrimidin-4-yl)-1-methyl-1H-indole (400 mg, 72percent).
71% With aluminum (III) chloride In 1,2-dichloro-ethane at 80℃; for 1.5 h; Intermediate 2a: 3-(2-chloropyrimidin-4-yl)-l-methyl-1H-indole (0131) (0132) To a 500mL single-necked flask were added 2,4-dichloropyrimidine (14.9 g, 100 mmol), 1-methyl-1H-indole (13 g, 100 mmol), 200 ml 1,2-dichloroethane and aluminium chloride (13.9 g, 120 mmol). The mixture was stirred at 80°C for 1.5 hours. The reaction mixture was cooled to room temperature in an ice bath. 120 ml methanol and 400 ml water were added to quench the reaction. A solid precipitated and was filtered. The filter cake was washed with methanol, and dried in vacuum to produce 17.2 g of a product with a yield of 71percent. MS m/z: 244 [M+1], 246. (0133) 1H NMR (400 MHz, DMSO-d6) δ 8.53 (d, J = 5.5 Hz, 1H), 8.49 (s, 1H), 8.42 (dd, J = 7.0, 1.5 Hz, 1H), 7.81 (d, J = 5.5 Hz, 1H), 7.56 (dd, J = 7.0, 1.2 Hz, 1H), 7.33 7.26 (m, 2H), 3.90 (d, J = 5.2 Hz, 3H)
62%
Stage #1: With aluminum (III) chloride In 1,2-dimethoxyethane at 20℃; for 0.25 h;
Stage #2: at 80℃;
This compound was prepared by the procedure of Finlay et al. 11 A suspension of 2,4-dichloropyrimidine (5.0 g, 33.6 mmol) and aluminum chloride (1.83 mL, 33.6 mmol) in DME (1,2-dimethoxyethane)(50 mL) was stirred at ambient temperature for 15 min. To this was added 1-methylindole (4.29 mL, 33.6 mmol), and the mixture was heated at 80 °C for 2–4 h. The cooled reaction mixture was added dropwise to vigorously stirring water (300 mL) over 20 min. Upon complete addition, the mixture was stirred for 30 min, filteredand the solid washed with water (250 mL). The crude product was purified by flash silica chromatography, eluting with DCM. Pure fractions were evaporated to dryness to afford 3-(2-chloropyrimidin-4-yl)-1-methylindole (5.08 g, 62percent) as a white solid. m.p. 201°C dec. (acetonitrile/water);1H NMR (CDCl3) δ 8.45 (m, 2H), 8.35 (m, 1H),7.37–7.95 (m, 4H), 3.89 (s, 3H); MS calcd for C13H10ClN3 [M]+ 243.1; found: 244.1
61%
Stage #1: With aluminum (III) chloride In 1,2-dimethoxyethane at 10℃; for 0.25 h;
Stage #2: for 2 h; Reflux
To a stirred suspension of 2,4-dichloropyrimidine (2.637 g, 20.13 mmol) in dimethoxyethane (30 mL) was added aluminum trichloride (2.67 g, 20.134 mmol) at 10 °C. The mixture was stirred at 10 °C for 15 mins. 1 -methyl- lH-indole (3.0 g, 20.13 mmol) was added, and the mixture was heated under reflux for 2 h. The mixture was cooled to RT, poured into water (30 mL) and extracted with ethyl acetate (3 x 50 mL). The combined organic layers were washed with water (30 mL) and brine (30 mL), dried over sodium sulphate and concentrated to afford 3-(2-chloropyrimidin-4-yl)-l-methyl-lH-indole (3.0 g, 12.34 mmol, 61percent). LC/MS (ESI) m/z 244.3 [M+H]+.
49% With iron(III) chloride In 1,2-dimethoxyethane at 60℃; 2,4-dichloropyrimidine (3 g, 20.1 mmol) was dissolved in DME (50 ml) and heated to 60 °C. FeCl3 (2953 mg, 22.1 mmol) added followed by 1-methylindole (2642 mg, 20.1 mmol) and reaction stirred at 60 °C overnight. Cooled to r.t. and poured into ice water, stirred for 30 minutes and the resulting precipitate collected by filtration. Purified by column chromatography eluting with DCM to provide 2.4 g (49percent) of 3-(2-chloropyrimidin-4-yl)-1-methyl-indole. NMR and LC-MS conform to structure and match literature reports
47% With iron(III) chloride In 1,2-dimethoxyethane at 64℃; Inert atmosphere Under nitrogen, 100mL three-mouthed flask successively add 002-2 (1.3g, 8.73mmol), 13mL DME, FeCl3 (1.414g, 8.72mmol) and 001-5 (974mg, 7.43mmol). In an oil bath at 64 deg.C react overnight. After completion of the reaction, the reaction mixture was down to room temperature, filtered, the filter cake washed 3 times with 20mL of methanol, the organic phases were combined and concentrated to dryness, and driedto give 1.0g 005-1 (47percent), as a yellow solid.
47% With iron(III) chloride In 1,2-dimethoxyethane at 64℃; Inert atmosphere Example 6 1. Synthesis of intermediate 006-2 The intermediate 001-5 (1.3 g, 8.73 mmol), 13 mL of DME, FeCl3 (1.414 g, 8.72 mmol) and the intermediate 006-1 (974 mg, 7.43 mmol) were added sequentially to a 100 mL three-necked flask under nitrogen atmosphere, and the reaction mixture was in an oil bath at 64°C overnight. After the reaction was completed, the reaction mixture was cooled to room temperature and filtered. The filter cake was washed three times with 20 mL of methanol and the organic phases were combined, concentrated to dryness and 1.0 g of intermediate 006-2 (47percent) was obtained as a yellow solid. LCMS: 244.1.
46%
Stage #1: With methylmagnesium bromide In diethyl ether; 1,2-dichloro-ethane at 0℃; for 0.25 h; Inert atmosphere
Stage #2: at 20℃; for 16 h;
In 10 minutes at 0 ° CN2 atmosphere,CH3MgBr (3M in ether, 22.68 mL, 68.03 mmol)Was added dropwise to a solution of 1-methyl-indole (7.97 g, 68.03 mmol)In 1,2-dichloroethane (250 mL)In the stirred solution.The resulting solution was stirred for 15 minutes,And then 2,4-dichloropyrimidine (15.00 g, 100.69 mmol) was added in one portion.The resulting solution was allowed to warm to room temperature and stirred for an additional 16 hours.The reaction was quenched by the addition of CH3OH (25 mL)The mixture was then concentrated in vacuo to allow it to adsorb onto silica gel.Using FCC for purification,Eluting with 0-20percent CH3OH in CH2Cl2,The title compound was obtained as a yellow solid (7.17 g, 46percent).

Reference: [1] Patent: CN106957304, 2017, A, . Location in patent: Paragraph 0013
[2] Patent: EP3181559, 2017, A1, . Location in patent: Paragraph 0048
[3] Patent: WO2013/14448, 2013, A1, . Location in patent: Page/Page column 160
[4] Patent: EP3205650, 2017, A1, . Location in patent: Paragraph 0119; 0120
[5] Patent: EP3181560, 2017, A1, . Location in patent: Paragraph 0131; 0132; 0133
[6] Journal of Medicinal Chemistry, 2014, vol. 57, # 20, p. 8249 - 8267
[7] Journal of Chemical Research, 2015, vol. 39, # 6, p. 318 - 320
[8] Patent: WO2017/205459, 2017, A1, . Location in patent: Paragraph 0175
[9] Patent: WO2018/119441, 2018, A1, . Location in patent: Paragraph 00890; 00891
[10] Patent: CN105237515, 2016, A, . Location in patent: Paragraph 0185; 0186; 0187
[11] Patent: EP3216786, 2017, A1, . Location in patent: Paragraph 0097-0099
[12] Patent: CN107043369, 2017, A, . Location in patent: Paragraph 0403; 0404; 0405; 0406
[13] Patent: CN108503627, 2018, A, . Location in patent: Paragraph 0095; 0097; 0099
[14] Patent: CN108658943, 2018, A, . Location in patent: Paragraph 0017; 0021; 0023
[15] European Journal of Medicinal Chemistry, 2019, p. 367 - 380
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YieldReaction ConditionsOperation in experiment
90.2% With potassium hydride In 1,2-dichloro-ethane at 50℃; for 8 h; 2-(4-(N-(2-(dimethylamino)ethyl)-N-methylamino)-2-methoxy-5-amino)-4-chloropyrimidine (5.4g, 15 . 4mmol) and 1 - methyl - 1H - indole (2.6g, 20 . 0mmol) dissolved in 1,2-dichloroethane (100 ml), by adding potassium hydride (1.0g, 24 . 6mmol), the reaction mixture 50 °C stirring reaction for 8 hours, TLC board determine the completion of the reaction, the reaction solution under reduced pressure to dry and concentration, adding ethyl acetate extraction, magnesium sulfate drying, and concentration to dry, ethanol and isopropanol mixed solvent crystallization, 2-(4-(N-(2-(dimethylamino)ethyl)-N-methylamino)-2-methoxy-5-aminophenylamino)-4-(1-methyl-1H-indole-3-yl)pyrimidine, pale yellow solid (6.2g), yield 90.2percent,
Reference: [1] Patent: CN106543060, 2017, A, . Location in patent: Paragraph 0069; 0070
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  • [ 1421372-66-8 ]
Reference: [1] Patent: WO2013/14448, 2013, A1,
[2] Journal of Medicinal Chemistry, 2014, vol. 57, # 20, p. 8249 - 8267
[3] Patent: EP3216786, 2017, A1,
[4] European Journal of Medicinal Chemistry, 2019, p. 367 - 380
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  • [ 1421372-94-2 ]
Reference: [1] Patent: WO2013/14448, 2013, A1,
[2] Journal of Medicinal Chemistry, 2014, vol. 57, # 20, p. 8249 - 8267
[3] Patent: CN107043369, 2017, A,
[4] Patent: EP3216786, 2017, A1,
[5] Patent: WO2017/205459, 2017, A1,
[6] Patent: WO2018/119441, 2018, A1,
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  • [ 603-76-9 ]
  • [ 1421373-65-0 ]
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[2] Patent: WO2013/14448, 2013, A1,
[3] Patent: WO2013/14448, 2013, A1,
[4] Journal of Medicinal Chemistry, 2014, vol. 57, # 20, p. 8249 - 8267
[5] Journal of Chemical Research, 2015, vol. 39, # 6, p. 318 - 320
[6] Patent: CN109134435, 2019, A,
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Reference: [1] Patent: WO2013/14448, 2013, A1,
[2] Patent: WO2013/14448, 2013, A1,
[3] Patent: WO2013/14448, 2013, A1,
[4] Journal of Medicinal Chemistry, 2014, vol. 57, # 20, p. 8249 - 8267
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