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[ CAS No. 3514-15-6 ] {[proInfo.proName]}

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Chemical Structure| 3514-15-6
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Product Details of [ 3514-15-6 ]

CAS No. :3514-15-6 MDL No. :MFCD06801062
Formula : C11H14N2 Boiling Point : -
Linear Structure Formula :- InChI Key :BMINWSYCLTUQSH-UHFFFAOYSA-N
M.W : 174.24 Pubchem ID :11401058
Synonyms :

Calculated chemistry of [ 3514-15-6 ]

Physicochemical Properties

Num. heavy atoms : 13
Num. arom. heavy atoms : 9
Fraction Csp3 : 0.27
Num. rotatable bonds : 2
Num. H-bond acceptors : 1.0
Num. H-bond donors : 1.0
Molar Refractivity : 55.77
TPSA : 16.96 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) : -6.07 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.29
Log Po/w (XLOGP3) : 1.82
Log Po/w (WLOGP) : 1.75
Log Po/w (MLOGP) : 1.55
Log Po/w (SILICOS-IT) : 1.94
Consensus Log Po/w : 1.87

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.45
Solubility : 0.622 mg/ml ; 0.00357 mol/l
Class : Soluble
Log S (Ali) : -1.8
Solubility : 2.79 mg/ml ; 0.016 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -3.69
Solubility : 0.036 mg/ml ; 0.000207 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.54

Safety of [ 3514-15-6 ]

Signal Word:Warning Class:
Precautionary Statements:P261-P264-P270-P271-P280-P301+P312-P302+P352-P304+P340-P305+P351+P338-P330-P332+P313-P337+P313-P362-P403+P233-P405-P501 UN#:
Hazard Statements:H302-H315-H319-H335 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 3514-15-6 ]

* 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.

  • Downstream synthetic route of [ 3514-15-6 ]

[ 3514-15-6 ] Synthesis Path-Downstream   1~84

  • 1
  • [ 61939-18-2 ]
  • [ 3514-15-6 ]
YieldReaction ConditionsOperation in experiment
93% With sodium hydroxide; LiAlH4 In tetrahydrofuran; methanol; water 1.c Preparation of 1-methyl-2-(methylaminomethyl)-1 H -indole c) 1-Methyl-2-(methylaminomethyl)-1H-indole A 3-liter 3-necked roundbottom flask equipped with overhead stirring was charged with N,1-dimethyl-1H-indole-2-carboxamide (23.45 g, 124.58 mmole) and anhydrous THF (170 mL). The solution was stirred while a solution of LiAlH4 in THF (1.0 M, 250 mL, 250 mmole) was added via syringe. Gas was evolved during the addition of the first 50 mL of LiAlH4 solution. When the addition was complete, the resulting light yellow solution was heated at gentle reflux. After 23 hr, the reaction was cooled in ice and quenched by the sequential dropwise addition of H2O (9.5 mL), 15% NaOH (9.5 mL), and H2O (28.5 mL). The mixture was stirred for 15 min, then was filtered through celite, and the filter pad was washed thoroughly with THF. The filtrate was concentrated and the residue was flash chromatographed on silica.gel (10% MeOH/CHCl3 containing 0.5% cone. NH4OH). The title compound (20.17 g, 93%) was obtained as a light yellow oil: 1H NMR (300 MHz, CDCl3) δ 7.56 (d, J = 7.8 Hz, 1 H), 7.02 - 7.35 (m, 3 H), 6.38 (s, 1 H), 3.88 (s, 2 H), 3.75 (s, 3 H), 2.49 (s, 3 H).
93% With lithium aluminium tetrahydride In tetrahydrofuran for 23h; Heating / reflux; 1.c Preparation 1; Preparation of 1-Methyl-2-(methylaminomethyl)indole; c) 1-Methyl-2-(methylaminomethyl)indole A 3-liter 3-necked roundbottom flask equipped with overhead stirring was charged with N,1-dimethylindole-2-carboxamide (23.45 g, 124.58 mmole) and anhydrous THF (170 mL). The solution was stirred while a solution of LiAlH4 in THF (1.0 M, 250 mL, 250 mmole) was added via syringe. Gas was evolved during the addition of the first 50 mL of LiAlH4 solution. When the addition was complete, the resulting light yellow solution was heated at gentle reflux. After 23 hr, the reaction was cooled in ice and quenched by the sequential dropwise addition of H2O (9.5 mL), 15% NaOH (9.5 mL). and H2O (28.5 mL). The mixture was stirred for 15 min, then was filtered through celite, and the filter pad was washed thoroughly with THF. The filtrate was concentrated and the residue was flash chromatographed on silica gel (10% MeOH/CHCl3 containing 0.5% conc. NH4OH). The title compound (20.17 g, 93%) was obtained as a light yellow oil: 1H NMR (300 MHz, CDCl3) δ 7.56 (d, J=7.8 Hz, 1H), 7.02-7.35 (m, 3H), 6.38 (s, 1H), 3.88 (s, 2H), 3.75 (s, 3H), 2.49 (s, 3H).
93% With lithium aluminium tetrahydride In tetrahydrofuran for 24h; Heating / reflux; 1.c A 3-liter 3-necked roundbottom flask equipped with overhead stirring was charged with N,1-dimethylindole-2-carboxamide (23.4 g, 124.6 mmole) and anhydrous THF (170 mL). The solution was stirred while a solution of LiAlH4 in THF (1.0 M, 250 mL, 250 mmole) was added via syringe. Gas was evolved during the addition of the first 50 mL of LiAlH4 solution. When the addition was complete, the resulting light yellow solution was heated at gentle reflux. After 24 hr, the reaction was cooled in ice and quenched by the sequential dropwise addition of H2O (9.5 mL), 15% NaOH (9.5 mL), and H2O (28.5 mL). The mixture was stirred for 15 min, then was filtered through celite, and the filter pad was washed thoroughly with THF. The filtrate was concentrated and the residue was flash chromatographed on silica gel (10% MeOH/CHCl3 containing 5% conc. NH4OH). The title compound (20.2 g, 93%) was obtained as a light yellow oil: MS (EI) m/e 175 (M+H)+.
80% With lithium aluminium tetrahydride In tetrahydrofuran for 5h; Heating;
73% With ammonium hydroxide; LiAlH4 In tetrahydrofuran; CHCl3/MeOH 1.b b b 1-Methyl-2-(methylaminomethyl)indole To a solution of N,1-dimethylindole-2-carboxamide (23.3 g, 124.2 mmole) in dry THF (400 mL) was added LiAlH4 (1.0 M in THF, 250 mL, 250 mmole). The reaction solution was heated to 70° C. under argon for 36 hr with stirring. The resulting white cloudy solution was allowed to cool to RT and then was submitted to a basic work-up according to the procedure of Micovic and Mihailovic (Micovic, V. M.; M. L. J. J. Org. Chem. 1956, 18, 1190). Purification by chromatography on silica gel (5% NH4OH in 9:1 CHCl3/MeOH) afforded the titled compound (15.8 g, 73%) as a colorless oil: MS (ES) m/e 175 (M+H)+.

  • 2
  • [ 18668-68-3 ]
  • [ 3514-15-6 ]
  • Buta-2,3-dienyl-methyl-(1-methyl-1H-indol-2-ylmethyl)-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
70% With <i>tert</i>-butylamine
  • 3
  • [ 3514-15-6 ]
  • [ 3355-28-0 ]
  • But-2-ynyl-methyl-(1-methyl-1H-indol-2-ylmethyl)-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
70% With <i>tert</i>-butylamine
  • 4
  • [ 3514-15-6 ]
  • [ 106-96-7 ]
  • Methyl-(1-methyl-1H-indol-2-ylmethyl)-prop-2-ynyl-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% With <i>tert</i>-butylamine
YieldReaction ConditionsOperation in experiment
entspr. Indolcarboxamid, LiAlH4;
entspr. Carboxamid, LiAlH4;
  • 6
  • [ 3167-49-5 ]
  • [ 3514-15-6 ]
  • 6-amino-<i>N</i>-methyl-<i>N</i>-(1-methyl-1<i>H</i>-indol-2-ylmethyl)-nicotinamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
72% With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; triethylamine In dichloromethane; N,N-dimethyl-formamide for 16h;
  • 7
  • trans-3-(3-pyridyl)acrylic acid [ No CAS ]
  • [ 3514-15-6 ]
  • (E)-N-Methyl-N-(1-methyl-1 H-indol-2-ylmethyl)-3-(pyridin-3-yl)acrylamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
40% With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; triethylamine In N,N-dimethyl-formamide
  • 8
  • [ 150-13-0 ]
  • [ 3514-15-6 ]
  • 4-amino-<i>N</i>-methyl-<i>N</i>-(1-methyl-1<i>H</i>-indol-2-ylmethyl)-benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
93% With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide for 12h;
  • 9
  • [ 3514-15-6 ]
  • [ 139223-62-4 ]
  • (E)-3-(4-aminophenyl)-N-methyl-N-(1-methyl-1 H-indol-2-ylmethyl)acrylamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
19% With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; triethylamine In N,N-dimethyl-formamide
  • 10
  • [ 3514-15-6 ]
  • [ 65-85-0 ]
  • <i>N</i>-methyl-<i>N</i>-(1-methyl-1<i>H</i>-indol-2-ylmethyl)-benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
91% With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide for 12h;
  • 11
  • [ 3514-15-6 ]
  • [ 171050-05-8 ]
  • (2S)-2-[(carbomethoxy)methyl]-N,4-dimethyl-N-[(1-methyl-1H-indol-2-yl)-methyl]-3-oxo-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine-7-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
92% With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide for 18h;
  • 12
  • [ 3514-15-6 ]
  • [ 175531-28-9 ]
  • (2R)-2-[(carbomethoxy)methyl]-N,4-dimethyl-N-[(1-methyl-1H-indol-2-yl)methyl]-3-oxo-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine-7-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
92% With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide for 18h;
  • 13
  • [ 3514-15-6 ]
  • [ 167837-43-6 ]
  • [ 335027-53-7 ]
  • 14
  • [ 3514-15-6 ]
  • (E)-3-(2-aminopyrimidin-5-yl)acrylic acid [ No CAS ]
  • (E)-3-(2-aminopyrimidin-5-yl)-N-methyl-N-(1-methyl-1 H-indol-2-ylmethyl)acrylamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
89% With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; triethylamine In N,N-dimethyl-formamide
  • 15
  • [ 3514-15-6 ]
  • 3-(6-aminopyridin-3-yl)propionic acid [ No CAS ]
  • 3-(6-amino-pyridin-3-yl)-<i>N</i>-methyl-<i>N</i>-(1-methyl-1<i>H</i>-indol-2-ylmethyl)-propionamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
5% With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; triethylamine In N,N-dimethyl-formamide
  • 16
  • [ 3514-15-6 ]
  • [ 446263-92-9 ]
  • 3-[(acetyl-methyl-amino)-methyl]-<i>N</i>-methyl-<i>N</i>-(1-methyl-1<i>H</i>-indol-2-ylmethyl)-benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
86% With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; triethylamine In dichloromethane; N,N-dimethyl-formamide at 20℃; for 16h;
  • 17
  • [ 3514-15-6 ]
  • 4-methyl-3-oxo-2,3,4,5-tetrahydro-1<i>H</i>-benzo[<i>e</i>][1,4]diazepine-7-carboxylic acid; hydrochloride [ No CAS ]
  • N,4-dimethyl-N-[(1-methyl-1H-indol-2-yl)methyl]-3-oxo-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine-7-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane; N,N-dimethyl-formamide for 18h;
  • 18
  • [ 3514-15-6 ]
  • 3-[(N-acetyl-N-methylamino)methyl]-4-aminobenzoic acid trifluoroacetate [ No CAS ]
  • N-[(2-amino-5-{N-methyl-N-[(1-methylindol-2-yl)methyl]carbamoyl}phenyl)methyl]-N-methylacetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
89% With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide for 12h;
89% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In DMF (N,N-dimethyl-formamide) at 20℃; for 12h; 2 N-[(2-amino-5-{N-methyl-N-[(1-methylindol-2-yl)methyl]carbamoyl}phenyl)methyl]-N-methylacetamide Example 2 Preparation of N-[(2-amino-5-{N-methyl-N-[(1-methylindol-2-yl)methyl]carbamoyl}phenyl)methyl]-N-methylacetamide To a stirred solution of 4-amino-3-[(N-methylacetylamino)methyl]benzoic acid trifluoro acetate (0.73 g, 2.17 mmole), from Procedure 3, in DMF (20 ML) at RT was added diisopropylethyl amine (0.83 ml, 4.78 mmole), HOBt (0.32 g, 2.39 mmole), 1-methyl-2-(methylaminomethyl)indole (0.40 g, 2.39 mmole) and finally EDC (0.45 g, 2.39 mmole).. After 12 hr, the reaction contents were poured onto H2O (100 ML) and extracted with EtOAc (2*100 ML).. The organic phases were combined and sequentially washed with H2O (100 ML) and brine.. Drying over Na2SO4 and purification on silica (CHCl3/CH3OH. 95:5) afforded the title compound (0.73 g, 89%) as a light yellow solid: MS (ES) m/e 379 (M+H)+.
  • 20
  • [ 3514-15-6 ]
  • [ 335030-42-7 ]
  • (E)-N-methyl-N-[(1-methyl-1 H-indol-2-ylmethyl)]-3-(5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
70% With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 12h;
  • 21
  • [ 3514-15-6 ]
  • (E)-3-(6-Amino-5-methyl-pyridin-3-yl)-acrylic acid; hydrochloride [ No CAS ]
  • [ 335027-95-7 ]
YieldReaction ConditionsOperation in experiment
With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 12h;
  • 22
  • [ 3514-15-6 ]
  • (E)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylic acid hydrochloride [ No CAS ]
  • [ 335028-13-2 ]
YieldReaction ConditionsOperation in experiment
88% With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 12h;
  • 23
  • [ 941605-13-6 ]
  • [ 3514-15-6 ]
  • N-methyl-N-(1-methyl-1H-indol-2-ylmethyl)-3-(5,7,8,9-tetrahydro-6-oxa-1,9-diaza-benzocyclohepten-3-yl)-acrylamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
25% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 35℃; 9 EDC (0.10 g, 0.52 mmol) was added to a solution of 3-(5,7,8,9-Tetrahydro-6-oxa- l,9-diaza-benzocyclohepten-3-yl)-acrylic acid hydrochloride (0.11 g, 0.43 mmol), HOBt (64 mg, 0.47 mmol), Methyl-(1 -methyl- lH-indol-2-ylmethyl)-amine (128 mg, 0.47 mmol) and (/-Pr)2EtN (0.36 mL, 2.15 mmol) in DMF (6 mL). The mixture was allowed to stir overnight at 35 0C. The mixture was cooled to 0 0C and diluted with H2O (15 mL) with rapid stirring. The resulting gummy precipitate was filtered, washed with H2O (30 mL) then with Et2O (20 mL). The solid was dissolved in dichloromethane (100 mL), washed with H2O(50 mL), brine (50 mL), dried over MgSO2 , and treated with charcoal. The mixture was filtered and the filtrate was passed through a plug of silica gel. The silica gel was washed with ethyl acetate (50 mL) then with 5% methanol: dichloromethane (50 mL). The combined organic fractions were concentrated to give an oil. The resulting oil was triturated with etheϖhexanes (20 mL) until the oil was converted to a beige solid. Yield: 40 mg (25%) as a mixture of amide rotamers; 1H NMR (400 MHz, DMSO-d6) δ 8.24 (br s, IH), 7.92 and 7.85 (2 x s, IH), 7.50 - 7.39 (m, 3H), 7.18 - 6.92 (m, 3H), 6.78 (br s, IH), 6.41 and 6.20 (2 x s, IH), 5.07 and 4.83 (2 x s, 2H), 4.52 and 4.45 (2 x s, 2H), 3.71 - 3.61 (m, 5H), 3.50 - 3.40 (m, 2H), 3.10 and 2.95 (2 x s, 3H); ESI MS m/z 311 [C22H24N4O2 + H]+
  • 24
  • 3-(4-methyl-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)-acrylic acid hydrochloride [ No CAS ]
  • [ 3514-15-6 ]
  • N-methyl-N-(1-methyl-1H-indol-2-ylmethyl)-3-(4-methyl-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)-acrylamide dihydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
42% Stage #1: 3-(4-methyl-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)-acrylic acid hydrochloride; 1-methyl-2-(methylaminomethyl)-1H-indole With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride at 40℃; Stage #2: With hydrogenchloride In diethyl ether Stage #3: With hydrogenchloride In diethyl ether; dichloromethane 11 EDC (0.21 g, 1.1 mmol) was added to a suspension of methyl-(2-methyl- benzofuran-3-ylmethyl)-amine (158 mg, 0.9 mmol) and 3-(4-Methyl-2,3,4,5-tetrahydro- lH-pyrido[2,3-e][l,4]diazepin-7-yl)-acrylic acid hydrochloride (201 mg, 0.75 mmol). The mixture was allowed to stir overnight at 40 °C. The mixture was cooled to 0 0C and diluted with H2O (6OmL) with rapid stirring. The resulting precipitate was filtered, washed with H2O (20 mL) then dried under high vacuum. The solid was then subjected to flash chromatography on silicia gel using 5% methonakdichloromethane. The fractions were collected and treated with 5 mL of 2.0M HCL in Et2O. The suspension was concentrated, triturated with Et2O (50 Ml then filtered to give a coupled solid, were coupled. The resulting solid was dissolved in methylene chloride (5 mL) and treated with 2M HCl in ether (0.75 mL, 1.5 mmol). The yellow precipitate was filtered, triturated with diethyl ether and dried under high vacuum to afford the title compound as a white solid (138 mg, 42%). 1H NMR (300 MHz, DMSO-d6) 11.92 (bs, IH) 8.43-8.17 (m, 2H), 7.53- 7.38 (m, 3H), 7.29-6.98 (m, 3H), 6.40 (s, IH), 5.05-4.84 (m, 2H), 4.55-4.63 (m, IH), 4.31-4.38 (IH), 3.64-3.80 (m, 6H), 3.33-3.45 (m, IH), 2.97-2.93 (m, 2H) 2.82-2.79 (m, 3H); MS (ESI) m/e 390 (C23H27N5O + H)+.
  • 25
  • [ 3514-15-6 ]
  • (E)-3-[6-(Acetylamino)-5-methylpyridin-3-yl]-N-methyl-N-(1-methyl-1H-indol-2-ylmethyl)acrylamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: hydroxybenzotriazole monohydrate; diisopropylethylamine; EDC / dimethylformamide / 12 h / 20 °C 2: 93 percent / NaHCO3 / tetrahydrofuran / 50 h / 60 °C
  • 27
  • [ 118618-61-4 ]
  • [ 3514-15-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 93 percent / diethyl ether; dioxane; H2O / 3 h / Ambient temperature 2: 80 percent / lithium aluminium hydride / tetrahydrofuran / 5 h / Heating
  • 28
  • [ 3514-15-6 ]
  • [ 814-68-6 ]
  • [ 335033-27-7 ]
YieldReaction ConditionsOperation in experiment
80% With triethylamine In dichloromethane for 2h; 23.a a) N-Methyl-N-(l-methyl-lH-indol-2-yhnethyl)acrylamide; A solution of memyl-(l-methyl-lH-mdol-2-ylmethyl)amine (2.00 g, 11.5 mmol) in CH2Cl2 (100 mL) was treated with acryloyl chloride (1.03 mL, 12.7 mmol) followed by Et3N (1.8 mL, 13 mmol). After stirring for 2 h, the solution was diluted with CH2Cl2 (100 mL) and washed with saturated aqueous NaHCO3 (200 mL). The aqueous layer was extracted with CH2Cl2 (200 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated to an orange oil. Purification by flash column chromatography (silica gel, CH2Cl2ZMeOH, 99.5:0.5 to 99:1) gave the title compound (2.10 g, 80%) as a tan oil: 1H NMR (300 MHz, CDCl3) δ 7.59-7.56 (m, IH), 7.32-7.19 (m, 2H)5 7.13-7.08 (m, IH), 6.66-6.57 (m, IH), 6.47-6.38 (m, 2H), 5.78-5.74 (m, IH), 4.88^.74 (m, 2H), 3.69 (s,3H), 3.06-2.97 (m, 3H); MS (ESI) m/e 229 (M + H)+.
76% With triethylamine In dichloromethane at -78 - -30℃; for 0.5h; 160.b b) N-METHYL-N-(L-METHYL-LH-INDOL-2-YLMETHYL)-ACRYLAMIDE Acryloyl chloride (5.13 mL, 63.1 mmol) was added dropwise to a stirred CH2C12 (100 mL) solution of methyl-(1-methyl-1H-indol-2-ylmethyl)-amine (10.0 g, 57.4 mmol) and triethylamine (12 mL, 86.1 mmol) AT-78 °C. The reaction mixture was warmed to-30 °C over 30 min and quenched with water. The reaction mixture was diluted with CH2C12 (100 mL), washed with dilute NAHC03, HCl and water, dried and evaporated to afford 9.91 g (76%) title COMPOUND.'H NMR (300 MHz, DMSO-D6) 8 7.44 (m, 2H), 7.12 (t, J= 7.2Hz, 1H), 7.00 (t, J= 7.2Hz, 1H), 6.81 (dd, J= 7.4 and 16.7Hz, 1H), 6.40 and 6.14 (rotamers, 2s, 1H), 6.20 (dd, J= 2.5 and 16.7Hz, 1H), 5.7 (m, 1H), 4.90 and 4.80 (rotamers, 2s, 2H), 3. 68 and 3.66 (rotamers, 2s, 3H), 3.00 and 2.96 (rotamers, 2s, 3H). MS (ESI) INULE : 229.1 (M+H) +.
With triethylamine In dichloromethane 76.a Preparation of (E)-N-methyl-N-(1-methyl-1 H -indol-2-ylmethyl)-3-[6-(phenylamino)pyridin-3-yl]acrylamide a) N-Methyl-N-(1-methyl-1H-indol-2-ylmethyl)acrylamide To a stirred solution of 1-methyl-2-(methylaminomethyl)-1H-indole (1.5 g, 8.6 mmole) and Et3N (1.35 mL, 9.6 mmole) in CH2Cl2 (75 mL) at 0 °C was added dropwise acryloyl chloride (0.77 mL, 9.5 mmole) over 5 minutes. After 2 h the reaction was washed with cold H2O, brine, dried (MgSO4) and concentrated under vacuum. The residue was used without further purification.
3 g With triethylamine In dichloromethane at -78℃; for 2h; To a stirred solution of compound 2 (4g, 22.9mmol ) in DCM (40ml ) were added triethylamine (2.32 g, 22.9 mmol )and acryloyl chloride 2a ( 2g, 22.9mmol ) at -78°C and the total reaction mixture stirred at - 78°C for 2h . Water was added and warmed to room temperature. Reaction mixture was extracted with ethyl acetate, dried over sodium sulphate and concentrated under vacuum. Crude material was purified by eluting with 60% ethyl acetate in pet ether to get the desired compound A (3 g). MS(ESI): m/z229(M+H)+
3 g With triethylamine In dichloromethane at -78℃; for 2h; Synthesis of Intermediate A Step-2 [0026] To a stirred solution of compound 2 (4 g, 22.9 mmol) in DCM (40 ml) were added triethylamine (2.32 g, 22.9 mmol) and acryloyl chloride 2a (2 g, 22.9 mmol) at -78° C. and the total reaction mixture stirred at -78° C. for 2 h. Water was added and warmed to room temperature. Reaction mixture was extracted with ethyl acetate, dried over sodium sulphate and concentrated under vacuum. Crude material was purified by eluting with 60% ethyl acetate in pet ether to get the desired compound A (3 g). MS (ESI): m/z 229 (M+H)+

  • 29
  • [ 118-90-1 ]
  • [ 3514-15-6 ]
  • [ 335059-00-2 ]
YieldReaction ConditionsOperation in experiment
37% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In DMF (N,N-dimethyl-formamide) at 20℃; 8 Example 8; Preparation of N,2-Dimethyl-N-[(1-methyl-1H-indol-2-yl)methyl]benzamide; a) N,2-Dimethyl-N-[(1-methyl-1H-indol-2-yl)methyl]benzamide EDC (0.22 g, 1.15 mmole) was added to a solution of ortho-toluic acid (0.15 g, 1.10 mmole), 1-methyl-2-(methylaminomethyl)indole (0.20 g, 1.15 mmole), and HOBt.H2O (0.15 g, 1.11 mmole) in DMF at RT. The reaction was stirred overnight, then was concentrated in vacuo. The residue was diluted with 5% NaHCO3 and extracted with CH2Cl2. The combined organic extracts were washed with brine and dried over MgSO4. Flash chromatography on silica gel (20% EtOAc/hexanes) gave a colorless gum, which was triturated with Et2O to afford the title compound (0.2 g, 37%) as a white solid: 1H NMR (300 MHz, CDCl3) indicated an approximately 5:1 mixture of amide rotamers; for the major rotamer: δ 7.60 (d, J=7.7 Hz, 1H), 7.05-7.40 (m, 7H), 6.52 (s, 1H), 5.01 (s, 2H), 3.85 (s, 3H), 2.71 (s, 3H), 2.30 (s, 3H); for the minor rotamer: δ 7.60 (d, J=7.7 Hz, 1H), 7.05-7.40 (m, 7H), 6.44 (s, 1H), 4.52 (s, 2H), 3.50 (s, 3H), 3.14 (s, 3H), 2.37 (s, 3H); MS (ES) m/e 293 (M+H)+. Anal. Calcd for C19H20N2O.0.35H2O: C, 76.40; H, 6.99; N, 9.38. Found: C, 76.10; H, 6.83; N, 9.33
  • 30
  • [ 3514-15-6 ]
  • [ 88-65-3 ]
  • [ 335059-15-9 ]
YieldReaction ConditionsOperation in experiment
63% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In DMF (N,N-dimethyl-formamide) at 20℃; Scheme I.a; 3.b Preparation 3; Preparation of 2-Bromo-N-methyl-N-[(1-methyl-1H-indol-2-yl)methyl]benzamide; a) 2-Bromo-N-methyl-N-[(1-methyl-1H-indol-2-yl)methyl]benzamide; Method II EDC (660 mg, 3.44 mmole) was added to a solution of 2-bromobenzoic acid (693 mg, 3.45 mmole), 1-methyl-2-(methylaminomethyl)indole (600 mg, 3.45 mmole), and HOBt.H2O (466 mg, 3.45 mmole) in DMF at RT. The reaction was stirred overnight, then was concentrated in vacuo. The residue was diluted with 5% NaHCO3 and extracted with CH2Cl2. The combined organic extracts were washed with brine and dried over MgSO4. Flash chromatography on silica gel (2% MeOH/CH2Cl2) gave the title compound (750 mg, 63%): MS (ES) m/e 357 (M+H)+.
  • 31
  • [ 3514-15-6 ]
  • [ 947-84-2 ]
  • [ 335058-94-1 ]
YieldReaction ConditionsOperation in experiment
25% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In DMF (N,N-dimethyl-formamide) at 20℃; 2 Example 2; Preparation of N-Methyl-N-[(1-methyl-1H-indol-2-yl)methyl]-2-phenylbenzamide; a) N-Methyl-N-[(1-methyl-1H-indol-2-yl)methyl]-2-phenylbenzamide EDC (0.22 g, 1.14 mmole) was added to a solution of 2-biphenylcarboxylic acid (0.22 g, 1.14 mmole), 1-methyl-2-(methylaminomethyl)indole (0.20 g, 1.15 mmole), and HOBt.H2O (0.15 g, 1.11 mmole) in DMF (20 mL) at RT. The reaction was stirred overnight, then was concentrated in vacuo. The residue was diluted with 5% NaHCO3 and extracted with CH2Cl2. The combined organic extracts were washed with brine and dried over MgSO4. Flash chromatography on silica gel (3% MeOH/CH2Cl2) followed by preparative TLC (3% MeOH/CH2Cl2) gave the title compound (0.10 g, 25%) as a light yellow solid: 1H NMR (360 MHz, CDCl3) indicated an approximately 5:1 mixture of amide rotamers; for the major rotamer: δ 7.03-7.58 (m, 13H), 6.19 (s, 1H), 4.50 -5.00 (m, 2H), 3.57 (s, 3H), 2.40 (s, 3H); for the minor rotamer: δ 7.03-7.58 (m, 13H), 6.14 (s, 1H), 4.50-5.00 (m, 2H), 3.38 (s, 3H), 2.76 (s, 3H); MS (ES) m/e 356 (M+H)+. Anal. Calcd for C24H22N2O.0.80H2O: C, 78.15; H, 6.45; N, 7.59. Found: C, 77.96; H, 6.29; N, 7.35.
  • 32
  • [ 3514-15-6 ]
  • [ 2243-42-7 ]
  • [ 335058-99-6 ]
YieldReaction ConditionsOperation in experiment
100% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In DMF (N,N-dimethyl-formamide); at 20℃; for 16.5h; EDC (230 mg, 1.2 mmole) was added to a solution of <strong>[2243-42-7]2-<strong>[2243-42-7]phenoxybenzoic acid</strong></strong> (214.2 mg, 1.0 mmole), 1-methyl-2-(methylaminomethyl)indole (209.1 mg, 1.2 mmole), HOBt.H2O (162.2 mg, 1.2 mmole), and triethylamine (0.35 mL, 2.5 mmole) in DMF (5 mL) at RT. After 16.5 hr, the reaction was concentrated, and the residue was reconcentrated from xylenes/CHCl3 to remove residual DMF. Flash chromatography on silica gel (40% EtOAc/hexanes) gave the title compound (393.5 mg, quantitative) as a nearly colorless, very viscous oil: 1H NMR (360 MHz, CDCl3) indicated an approximately 5:1 mixture of amide rotamers; for the major rotamer: delta 7.56 (d, J=7.9 Hz, 1H), 6.98-7.50 (m, 9H), 6.95 (d, J=7.6 Hz, 2H), 6.87 (d, J=7.5 Hz, 1H), 6.49 (s, 1H), 4.40-5.40 (m, 2H), 3.62 (s, 3H), 2.84 (s, 3H); for the minor rotamer: delta 6.80-7.50 (m, 13H), 6.47 (s, 1H), 4.40-5.40 (m, 2H), 3.56 (s, 3H), 2.98 (s, 3H); MS (ES) m/e 371 (M+H)+.
  • 33
  • 4-amino-2-phenoxy-benzoic acid ; hydrochloride [ No CAS ]
  • [ 3514-15-6 ]
  • [ 335059-10-4 ]
YieldReaction ConditionsOperation in experiment
42% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In DMF (N,N-dimethyl-formamide); dichloromethane at 20℃; for 16h; 18 Example 18; Preparation of 4-Amino-N-methyl-N-(1-methyl-1H-indol-2-ylmethyl)-2-phenoxybenzamide To 4-amino-2-phenoxybenzoic acid hydrochloride (1.0 g, 3.4 mmole) in 1:1 DMF/CH2Cl2 (75 mL) was added 1-methyl-2-(methylaminomethyl)indole (0.61 g, 3.5 mmole), HOBt.H2O (0.47 g, 3.5 mmole), Et3N (1.0 mL, 7.1 mmole), then EDC (0.67 g, 3.5 mmole). The reaction was stirred at RT for 16 hr then was concentrated under vacuum. The residue was taken up in EtOAc (200 mL) and-the solution was washed with water, dried (Na2SO4), and concentrated. Flash chromatography on silica gel (2% MeOH/CHCl3, then rechromatography using 70% EtOAc/hexanes) gave the title compound (0.62 g, 42%) as a white solid: MS (ES) m/e 386.2 (M+H)+.
  • 34
  • [ 106841-63-8 ]
  • [ 3514-15-6 ]
  • [ 335059-11-5 ]
YieldReaction ConditionsOperation in experiment
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In DMF (N,N-dimethyl-formamide)
  • 35
  • [ 734524-98-2 ]
  • [ 3514-15-6 ]
  • [ 335059-10-4 ]
YieldReaction ConditionsOperation in experiment
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In DMF (N,N-dimethyl-formamide)
  • 36
  • [ 36040-17-2 ]
  • [ 3514-15-6 ]
  • [ 335058-93-0 ]
YieldReaction ConditionsOperation in experiment
90% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In DMF (N,N-dimethyl-formamide) at 20℃; Scheme II.c; 1 Example 1; Preparation of 2-[2-(4-Methoxyphenyl)ethyl]-N-methyl-N-[(1-methyl-1H-indol-2-yl)methyl]nicotinamide; a) 2-[2-(4-Methoxyphenyl)ethyl]-N-methyl-N-[(1-methyl-1H-indol-2-yl)methyl]nicotinamide EDC (0.60 g, 3.16 mmole) was added to a solution of 2-[2-(4-methoxyphenyl)ethyl]nicotinic acid (0.81 g, 3.16 mmole), 1-methyl-2-(methylaminomethyl)indole (0.50 g, 2.87 mmole), HOBt.H2O (0.43 g, 3.16 mmole), and diisopropylethylamine (0.55 mL, 3.16 mmole) in DMF (15 mL) at RT. The reaction was stirred overnight, then was diluted with H2O and extracted with EtOAc. Drying (Na2SO4), concentration, and flash chromatography on silica gel (5% MeOH/CHCl3) gave the title compound (1.07 g, 90%) as a viscous yellow oil: 1H NMR (300 MHz, DMSO-d6) δ 8.63 (m, 1H), 7.22-7.61 (m, 8H), 6.97 (d, J=8.1 Hz, 1H), 6.63 (d, J=8.1 Hz, 1H), 6.52 (s, 1H), 3.80 (s, 3H), 3.78 (m, 2H), 3.72 (s, 2H), 3.16 (m, 2H), 3.03 (s, 3H), 2.57 (s, 3H), MS (ES) m/e 414 (M+H)+. Anal. Calcd for C26H27N3O2: C, 75.52; H, 6.58: N, 10.16. Found C, 75.84; H, 6.68; N, 9.76.
  • 37
  • [ 3514-15-6 ]
  • [ 7154-66-7 ]
  • [ 335059-15-9 ]
YieldReaction ConditionsOperation in experiment
87% With triethylamine In dichloromethane at 0 - 20℃; for 2.25h; 3.a Preparation 3; Preparation of 2-Bromo-N-methyl-N-[(1-methyl-1H-indol-2-yl)methyl]benzamide; a) 2-Bromo-N-methyl-N-[(1-methyl-1H-indol-2-yl)methyl]benzamide; Method I A solution of 2-bromobenzoyl chloride (1.85 g, 8.45 mmole) in CH2Cl2 (10 mL) was added dropwise to a solution of 1-methyl-2-(methylaminomethyl)indole (1.47 g, 8.45 mmole) and Et3N (3.6 mL, 25.8 mmole) in CH2Cl2 (50 mL) at 0° C. The reaction was stirred at 0° C. for 15 min, then was allowed to warm to RT. After 2 hr, the mixture was concentrated in vacuo, and the residue was diluted with H2O. The mixture was extracted with Et2O, and the combined Et2O layers were dried (MgSO4) and concentrated in vacuo. The oily residue was triturated with Et2O/petroleum ether to afford the title compound (2.6 g, 87%) as a white solid: MS (ES) m/e 357 (M+H)+.
  • 38
  • tert-butyl 3-[(phenylamino)methyl]-4-nitro benzoic acid trifluoroacetate salt [ No CAS ]
  • [ 3514-15-6 ]
  • [ 334999-87-0 ]
YieldReaction ConditionsOperation in experiment
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; diethylamine In DMF (N,N-dimethyl-formamide) at 20℃; for 12h; 1.b To a stirred solution of the above compound in DMF (30 mL) at RT was added diethyl amine (1.7 mL, 12.1 mmole), 1-methyl-2-(methylaminomethyl)indole (1.0 g, 6.0 mmole), HOBt (0.81 g, 6.0 mmole) and finally EDC (1.15 g, 6.0 mmole). After 12 hr, the reaction contents were poured onto H2O (100 mL) and extracted with EtOAc (2x100 mL). The organic phases were combined and sequentially washed with H2O (100 mL) and brine. Drying over Na2SO4 and purification on silica (EtOAc) afforded the title compound (2.33 g, 92%) as a solid yellow foam: MS (ES) m/e 429 (M+H)+.To a stirred solution of tert-butyl 3-[(phenylamino)methyl]-4-nitro benzoate (1.95 g, 4.55 mmole) in CHCl2 (20 mL) at RT was added TFA (20 mL). After 12 hr, the reaction contents were concentrated, treated with 4M aqueous HCl, dioxane (10 mL) and concentrated under vacuum affording a tan solid. The solid residue was washed with hexanes and dried under high vacuum. This product was used directly in the next step without further purification.
  • 39
  • [ 334999-83-6 ]
  • [ 3514-15-6 ]
  • [ 334999-84-7 ]
YieldReaction ConditionsOperation in experiment
92% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In DMF (N,N-dimethyl-formamide) at 20℃; for 12h; 11.c To a stirred solution of 4-nitro-3-[(N-methyl(phenylmethoxy)carbonylamino]methyl}benzoic acid (4.56 g, 13.26 mmole) in DMF (20 mL) at RT was added diisopropylethyl amine (2.31 mL, 13.26 mmole), HOBt (1.79 g, 13.26 mmole), 1-methyl-2-(methylaminomethyl)indole (2.1 g, 12.0 mmole) and finally EDC (2.54 g, 13.26 mmole). After 12 hr, the reaction contents were poured onto H2O (100 mL) and extracted with EtOAc (2*100 mL). The organic phases were combined and sequentially washed with H2O (100 mL) and brine. Drying over Na2SO4 and purification on silica (hexanes/EtOAc, 1:1) afforded the title compound (5.52 g, 92%) as a viscous yellow oil: MS (ES) m/e 501 (M+H)+.
  • 40
  • [ 3514-15-6 ]
  • [ 175531-28-9 ]
  • (2R)-2-[(Carbomethoxy)methyl]-N,4-dimethyl-N-[(1-methyl-1H-indol-2-yl)methyl]-3-oxo-2,3,4,5-tetrahydro-1H-1,4benzodiazepine-7-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
92% With i-Pr2NEt; benzotriazol-1-ol; 1,2-dichloro-ethane In N,N-dimethyl-formamide 1.a a a (2R)-2-[(Carbomethoxy)methyl]-N,4-dimethyl-N-[(1-methyl-1H-indol-2-yl)methyl]-3-oxo-2,3,4,5-tetrahydro-1H-1,4benzodiazepine-7-carboxamide To a solution of (2R)-2-[(carbomethoxy)methyl]-4-methyl-3-oxo-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine-7-carboxylic acid (0.4 g, 1.37 mmole) in dry DMF (10 mL) at RT was added 1-methyl-2-(methylaminomethyl)indole (0.26 g, 1.50 mmole), HOBt (0.20 g, 1.50 mmole), i-Pr2NEt (0.19 g, 1.50 mmole) and EDC (0.29 g, 1.50 mmole). After 18 hr the reaction solution was diluted with H2O (25 mL) and extracted with EtOAc (2*50 mL). The organic fractions were combined, washed sequentially with H2O and brine, then were dried (Na2SO4). Concentration under vacuum followed by chromatography on silica gel (95:5 CHCl3/MeOH) provided the title compound (0.56 g, 92%) as an off-white solid: MS (ES) m/e 449 (M+H)+.
  • 41
  • [ 61939-18-2 ]
  • [ 7732-18-5 ]
  • [ 3514-15-6 ]
YieldReaction ConditionsOperation in experiment
20% With lithium aluminium tetrahydride In tetrahydrofuran 26.c c c 1-Methyl-2-(methylamino)methylindole LAH (50 mL, 1M solution in THF) was added dropwise through a syringe to a solution of 1-methyl-2-(methylaminocarbonyl)indole (2.33 g, 12.4 mmol) in anhydrous THF (10 mL) with cooling, and the resulting solution was stirred at RT under argon overnight. H2 O was added dropwise with cooling to destroy excess LAH, and the colorless precipitate was removed by filtration and washed with THF. The filtrate was dried (K2 CO3), concentrated, and purified by silica gel flash chromatography to afford the title compound (430 mg, 20% yield) as a yellow solid. MS (ES) m/e 175 (M+H)+.
  • 42
  • [ 894852-15-4 ]
  • [ 3514-15-6 ]
  • (E)-3-[6-amino-5-(1-hydroxy-1-methyl-ethyl)-pyridin-3-yl]-N-methyl-N-(1-methyl-1H-indol-2-ylmethyl)-acrylamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
79.5% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 35℃; 31 Example 31; Preparation of (^-S-f-Amino-S-Cl-hvdroxy-l-methyl-ethvD-pyridin-S-yll-N-methyl-N-fl- rnethyl- 1 H-indol-2-ylmethyl V acrylamide; EDC (0.13 g, 0.70 mmol) was added to a suspension of (£)-3-[6-Amino-5-(l- hydroxy-l-methyl-ethyl)-pyridin-3-yl]-acrylic acid hydrochloride (0.15 g, 0.58 mmol), HOBt (0.09 g, 0.64 mmol), Methyl-(l-methyl-lH-indol-2-yhnethyl)-amine (0.11 g, 0.64 mmol) and (/-Pr)2EtN (0.49 mL, 2.9 mmol) in DMF (8 mL). The mixture was allowed to stir overnight at 35 0C. The mixture was cooled to 00C and diluted with H2O (60 mL) with rapid stirring. The resulting precipitate was filtered, washed with H2O (20 mL) then dried under high vacuum. The solid was then triturated with Et2O, and the resultant white solid was collected, to yield 36 mg of product. An extraction on the original filtrate was done using EtOAc (2 x 75 mL) and the combined organic layers were washed with brine (100 mL), dried over MgSO4, and concentrated in vacuo. The resulting off-white solid was subjected to flash chromatography on silica gel using 10% methanol : dichloromethane. Yield: 138 mg (79.5%); 1HNMR (300 MHz, DMSO-(I6) δ 8.14 (s, IH), 7.68 (s, IH), 7.52- 7.40 (m, 3H), 7.15-6.98 (m, 3H), 6.58 (s, 2H), 6.41 and 6.25 (2 x s, IH), 5.49 (s, IH), 5.04 and 4.85 (2 x s, 2H), 3.69 (s, 3H), 3.10 and 2.98 (2 x s, 3H), 1.53 (s, 6H); ESIMS m/z 379 [C22H26N4O2 + H]+
  • 43
  • [ 941605-09-0 ]
  • [ 3514-15-6 ]
  • (E)-3-(5-hydroxy-6,6-dimethyl-7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)-N-methyl-N-((1-methyl-1H-indol-2-yl)methyl)acrylamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
46% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 40℃; for 17h; 53 EDC (154 mg, 0.81 mmol) was added to a suspension of (E)-3-(5-hydroxy-6,6-dimethyl-7-oxo- 5,6,7,8-tetrahydro-l,8-naphthyridin-3-yl)acrylic acid hydrochloride (200 mg, 0.67 mmol), HOBt (100 mg, 0.74 mmol), N-methyl(l -methyl- lH-mdol-2-yl)methanamine (129 mg, 0.74 mmol) and (/-Pr)2EtN (0.57 mL, 3.3 mmol) in DMF (8 mL). The mixture was allowed to stir for 17h at 40 0C. The mixture was cooled to room temperature and diluted with water (25 mL) to yield a brown precipitate, which was collected by suction filtration. The solid was then triturated with diethyl ether to obtain the crude product which was subjected to flash silica gel column chromatography with an 85:15 (DCM:MeOH) solvent ratio to obtain the product as a light brown solid. Yield: 130 mg (46%); 1H NMR (300 MHz, DMSOd6) δ 10.68 (s, IH), 8.44 (s, IH), 8.12 (s, IH), 7.66-6.96 (m, 6H), 6.35 (s, IH), 5.65 (bs, IH), 4.93 (s, 2H), 4.33 (s, IH), 3.73 (s, 3H), 3.11 (s, 3H), 1.04 (m, 6H); ESI MS m/z 419 [C24H26N4O3+ H]+
  • 44
  • [ 941604-87-1 ]
  • [ 3514-15-6 ]
  • N-methyl-N-(1-methyl-1H-indol-2-ylmethyl)-3-(8-oxo-5,7,8,9-tetrahydro-6-oxa-1,9-diazabenzocyclohepten-3-yl)-acrylamide hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
68% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 40℃; 7.e EDC (0.21 g, 1.1 mmol) was added to a suspension of 3-(8-Oxo-5,7,8,9-tetrahydro-6- oxa-l,9-diaza-benzocyclohepten-3-yl)-acrylic acid hydrochloride (0.25 g, 0.9 mmol), ηOBt (0.14 g, 1.0 mmol), Methyl-(1 -methyl- lH-indol-2-ylmethyl)-amine (0.18 g, 1.0 mmol) and (i- Pr)2EtN (0.9 mL, 5.5 mmol) in DMF (20 mL). The mixture was allowed to stir overnight at 40 0C. The mixture was cooled to 0 0C and diluted with H2O (60 mL) with rapid stirring. The resulting precipitate was filtered, washed with H2O (20 mL) then dried under high vacuum. The solid was then subjected to flash chromatography on silica gel using 5% methanol :dichloromethane. The fractions were collected and treated with 5 mL of 2.0M HCl in Et2O. The suspension was concentrated, triturated with Et2O (5OmL) then filtered to give a beige solid as a mixture of amide rotamers. Yield: 0.2 g (68%); 1H NMR (300 MHz, DMSO-de) δ 10.59 and 10.56 (2 x s, IH), 8.55 and 8.52 (2 x s, IH), 8.11 and 8.04 (2 x s, IH), 7.61 - 7.00 (m, 6H), 6.44 and 6.22 (2 x s, IH), 6.43 (br s, IH), 5.07 and 4.87 (2 x s, 2H), 4.80 and 4.75 (2 x s, 2H), 4.55 and 4.52 (2 x s, 2H), 3.73 and 3.70 (2 x s, 3H), 3.13 and 3.00 (2 x s, 3H); ESI MS m/z 391 [C22H23N4O3 + H]+
  • 45
  • 3-(5-hydroxy-7-oxo-7,8-dihydro-[1,8]naphthyridin-3-yl)-acrylic acid [ No CAS ]
  • [ 3514-15-6 ]
  • 3-(5-hydroxy-7-oxo-7,8-dihydro-[1,8]naphthyridin-3-yl)-N-methyl-N-(1-methyl-1H-indol-2-ylmethyl)-acrylamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
47% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide for 17h; 13.e EDC (231 mg, 1.2 mmol) was added to a solution of 3-(5-hydroxy-7-oxo-7,8-dihydro-[l,8]naphthyridin-3-yl)-acrylic acid (233 mg, 1.0 mmol), methyl-(l -methyl- lH-indol-2- ylmethyl)-amne (192 mg, 1.1 mmol), HOBt • H2O (150 mg. 1.1 mmol) and DIPEA (700 μL, 4.0 mmol) in dry DMF (10 mL). After 17 hr of stirring, the mixture was diluted with water (50 mL), washed with EtOAc (2x10 mL) and acidified. The precipitate was filtered, washed with water and dried to afford the title compound (184 mg, 47%). 1H NMR (300 MHz, DMSO-d6, δ): 11.7 (m, 2H), 8.85 and 8.81 (rotamers, 2s, IH), 8.51 and 8.46 (rotamers, 2s, IH), 7.67 (d, J =15.5 Hz, IH), 7.55-7.35 (m, 3H) 7.12 (m, IH), 7.01 (m, IH), 6.43 and 6.20 (rotamers, 2s, IH), 5.78 and 5.75 (rotamers, 2s, IH), 5.10 and 4.86 (rotamers, 2s, 2H), 3.73 and 3.69 (rotamers, 2s, 3H), 3.14 and 2.99 (rotamers, 2s, 3H). MS (ESI) m/e 389 (M+H)+.
YieldReaction ConditionsOperation in experiment
92% 49.a Preparation of 1,5-dimethyl-3-(methylaminomethyl)-1 H -indole a) 1,5-Dimethyl-1H-indole According to the method of Preparation 1 (a), except substituting 5-methylindole for ethyl indole-2-carboxylate, the title compound (92%) was prepared as an amber oil: MS (ES) m/e 146.2 (M + H)+.
  • 47
  • [ 180530-15-8 ]
  • [ 3514-15-6 ]
  • [ 335029-38-4 ]
YieldReaction ConditionsOperation in experiment
43% 64 Preparation of (E)-3-[2-(acetylamino)pyrimidin-5-yl]-N-methyl-N-(1-methyl-1 H -indol-2-ylmethyl)acrylamide Example 64 Preparation of (E)-3-[2-(acetylamino)pyrimidin-5-yl]-N-methyl-N-(1-methyl-1 H -indol-2-ylmethyl)acrylamide According to the procedure of Example 31, except substituting 1-methyl-2-(methylaminomethyl)indole (1.45 g, 8.33 mmole) for 3-methyl-2-(methylaminomethyl)indene hydrochloride, and substituting 2-acetylamino-5-bromopyrimidine (1.20 g, 5.55 mmole) for 6-bromo-3,4-dihydro-1H-1,8-naphthyridin-2-one, the title compound (2.38 g, 43%) was prepared as a yellow solid: MS (ES) m/e 364 (M + H)+.
  • 48
  • HOBt · H2O [ No CAS ]
  • [ 3514-15-6 ]
  • [ 167837-43-6 ]
  • [ 335027-53-7 ]
YieldReaction ConditionsOperation in experiment
83% With 1,2-dichloro-ethane; triethylamine; In N,N-dimethyl-formamide; Example 1 Preparation of (E)-3-(6-aminopyridin-3-yl)-N-methyl-N-(1-methyl-1 H -indol-2-ylmethyl)acrylamide EDC (0.70 g, 3.7 mmole) was added to a solution of <strong>[167837-43-6](E)-<strong>[167837-43-6]3-(6-aminopyridin-3-yl)acrylic acid</strong></strong> (0.61 g, 3.7 mmole), 1-methyl-2-(methylaminomethyl)-1H-indole (0.65 g, 3.7 mmole), HOBt · H2O (0.50 g, 3.7 mmole), and triethylamine (0.52 mL, 3.7 mmole) in DMF (30 mL) at RT. The reaction was stirred overnight, then was concentrated in vacuo. The residue was diluted with 5% NaHCO3 and extracted with CH2Cl2. The combined organic extracts were washed with brine and dried over MgSO4. Flash chromatography on silica gel (3% MeOH/CH2Cl2) gave a colorless semisolid which was triturated with Et2O and dried. The title compound (1.0 g, 83%) was obtained as a white solid: 1H NMR (300 MHz, CDCl3) delta 8.20 (br s, 1 H), 7.45 - 7.70 (m, 3 H), 7.00 - 7.30 (m, 3 H), 6.69 (d, J = 15.4 Hz, 1 H), 6.30 - 6.50 (m, 2 H), 4.89 (s, 2 H), 4.67 (br s, 2 H), 3.68 (s, 3 H), 3.01 (s, 3 H); MS (ES) m/e 321 (M + H)+. Anal. Calcd for C19H20N4O · 0.40 H2O: C, 69.66; H, 6.40; N, 17.10. Found: C, 69.99; H, 6.27; N, 16.84.
  • 49
  • (E)-3-(6-aminopyridin-3-yl)-2-methylacrylic acid HCl salt [ No CAS ]
  • HOBt · H2O [ No CAS ]
  • [ 3514-15-6 ]
  • [ 335029-03-3 ]
YieldReaction ConditionsOperation in experiment
75% With 1,2-dichloro-ethane; triethylamine In dichloromethane; ethyl acetate; N,N-dimethyl-formamide 52 Preparation of (E)-3-(6-aminopyridin-3-yl)-2-methyl-N-methyl-N-(1-methyl-1H-indol-2-ylmethyl)acrylamide Example 52 Preparation of (E)-3-(6-aminopyridin-3-yl)-2-methyl-N-methyl-N-(1-methyl-1H-indol-2-ylmethyl)acrylamide To a stirred solution of (E)-3-(6-aminopyridin-3-yl)-2-methylacrylic acid HCl salt (0.5 g, 2.3 mmole) in dry 1:1 DMF/CH2Cl2 (30 mL) at RT was added 1-methyl-2-(methylaminomethyl)indole (0.42 g, 2.4 mmole), HOBt · H2O (0.32 g, 2.4 mmole), Et3N (0.66 mL, 4.7 mmole), and EDC (0.46 g, 2.4 mmole). After stirring for 24 hr the reaction was concentrated to dryness. The residue was taken up in ethyl acetate and the solution was washed with H2O, dried (Na2SO4), and concentrated under vacuum. Flash chromatography on silica gel (4% methanol/CHCl3) followed by trituration with ethyl acetate/hexane gave the title compound (0.55 g, 75%) as an off-white solid: LCMS (ES)m/e 335.2 (M + H)+; 1H NMR (300 MHz, DMSO-d6) δ 7.96 (s, 1 H), 7.52 (d, J = 7.8 Hz, 1 H), 7.48 (dd, 1 H), 7.43 (d, J = 7.8 Hz, 1 H), 7.14 (t, 1 H), 7.03 (t, 1 H), 6.46 (d, J = 8.7 Hz, 1 H), 6.43 (s, 1 H), 6.40 (s, 1 H), 6.17 (br s, 2 H).
  • 50
  • 5-bromo-2 H -pyrido[3,2- b ]-1,4-oxazin-3(4 H)-one [ No CAS ]
  • [ 3514-15-6 ]
  • [ 335029-47-5 ]
YieldReaction ConditionsOperation in experiment
53% 67 Preparation of (E)-N-methyl-N-(1-methyl-1 H -indol-2-ylmethyl)-3-(3-oxo-3,4-dihydro-2 H -pyrido[3,2- b ]-1,4-oxazin-7-yl)acrylamide Example 67 Preparation of (E)-N-methyl-N-(1-methyl-1 H -indol-2-ylmethyl)-3-(3-oxo-3,4-dihydro-2 H -pyrido[3,2- b ]-1,4-oxazin-7-yl)acrylamide According to the procedure of Example 31, except substituting 1-methyl-2-(methylaminomethyl)indole (1.17 g, 6.75 mmole) for 3-methyl-2-(methylaminomethyl)indene hydrochloride, and substituting 5-bromo-2H-pyrido[3,2-b]-1,4-oxazin-3(4H)-one (1.03 g, 4.50 mmole) for 6-bromo-3,4-dihydro-1H-1,8-naphthyridin-2-one, the title compound (0.90 g, 53%) was prepared as a light yellow solid: MS (ES) m/e 377 (M + H)+.
  • 51
  • [ 335030-34-7 ]
  • HOBt · H2O [ No CAS ]
  • [ 3514-15-6 ]
  • [ 335027-65-1 ]
YieldReaction ConditionsOperation in experiment
66% With 1,2-dichloro-ethane; triethylamine In N,N-dimethyl-formamide 5.a Preparation of (E)-3-(3,4-dihydro-2 H -pyrido[3,2- b ]-1,4-oxazin-7-yl)-N-methyl-N-(1-methyl-1 H -indol-2-ylmethyl)acrylamide a) (E)-3-(3,4-Dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)-N-methyl-N-(1-methyl-1H-indol-2-ylmethyl)acrylamide EDC (230 mg, 1.2 mmole) was added to a solution (E)-3-(3,4-dihydro-2H-pyrido[3,2-b]-1,4-oxazin-7-yl)acrylic acid (206 mg, 1.0 mmole), 1-methyl-2-(methylaminomethyl)-1H-indole (209 mg, 1.2 mmole), HOBt · H2O (162 mg, 1.2 mmole), and Et3N (0.21 mL, 1.5 mmole) in dry DMF (5 mL) at RT. After 18 hr the mixture was concentrated. Flash chromatography on silica gel (5% EtOH/EtOAc) gave the title compound (238 mg, 66%) as a yellow solid: 1H NMR (400 MHz, d6-DMSO) δ 7.99-6.95 (m, 8 H), 6.40 (s, 1 H), 4.82 (s, 2 H), 4.11 (bs, 2 H), 3.72 (bs, 3 H), 3.67 (bs, 2 H), 3.08 (s, 3 H); for minor rotomer δ 6.15 (s, 1 H), 5.02 (s, 2 H), 2.96 (s, 3 H); MS (ES) m/e 363 (M + H)+.
  • 52
  • HOBt · H2O [ No CAS ]
  • [ 3514-15-6 ]
  • [ 335030-42-7 ]
  • (E)-N-methyl-N-[(1-methyl-1 H-indol-2-ylmethyl)]-3-(5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
70% With 1,2-dichloro-ethane; triethylamine In N,N-dimethyl-formamide 6.a Preparation of (E)-N-methyl-N-[(1-methyl-1 H -indol-2-ylmethyl)]-3-(5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylamide a) (E)-N-Methyl-N-[(1-methyl-1H-indol-2-ylmethyl)]-3-(5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylamide EDC (203 mg, 1.06 mmole) was added to a solution (E)-3-(5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylic acid (180 mg, 0.88 mmole), 1-methyl-2-(methylaminomethyl)-1H-indole (185 mg, 1.06 mmole), HOBt · H2O (143 mg, 1.06 mmole), and Et3N (0.31 mL, 2.2 mmole) in dry DMF (5 mL) at RT. After 18 hr the mixture was concentrated. Flash chromatography on silica gel (10% EtOH/EtOAc) gave the title compound (222 mg, 70%) as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ 7.99-6.82 (m, 8 H), 6.40 (s, 1 H), 4.82 (s, 2 H), 3.67 (m, 2 H), 3.29 (m, 3 H), 3.07 (m, 3 H), 2.73 (m, 2 H), 1.77 (m, 2 H); for minor rotomer δ 6.16 (s, 1 H), 5.00 (s, 2 H); MS (ES) m/e 361 (M + H)+.
  • 53
  • HOBt · H2O [ No CAS ]
  • [ 335030-65-4 ]
  • [ 3514-15-6 ]
  • [ 335027-77-5 ]
YieldReaction ConditionsOperation in experiment
With 1,2-dichloro-ethane; triethylamine In N,N-dimethyl-formamide 9.a Preparation of (E)-3-(3 H -imidazo[4,5- b ]pyridin-6-yl)-N-methyl-N-(1-methyl-1 H -indol-2-ylmethyl)acrylamide a) (E)-3-(3H-Imidazo[4,5-b]pyridin-6-yl)-N-methyl-N-(1-methyl-1H-indol-2-ylmethyl)acrylamide EDC (230 mg, 1.2 mmole) was added to a solution (E)-3-(3H-imidazo[4,5-b]pyridin-6-yl)acrylic acid (189 mg, 1.0 mmole), 1-methyl-2-(methylaminomethyl)-1H-indole (209 mg, 1.2 mmole), HOBt · H2O (162 mg, 1.2 mmole), and Et3N (0.28 mL, 2.0 mmole) in dry DMF (5 mL) at RT. After 18 hr the mixture was diluted with H2O. The title compound (193 mg, 56%) was collected as a white solid by filtration, washed with H2O, and dried in vacuo: 1H NMR (400 MHz, d6-DMSO) δ 8.72 (s, 1 H), 8.50 (s, 2 H), 7.68 (d, J = 15.4 Hz, 1 H), 7.45 (m, 3 H), 7.13 (m, 1 H), 7.01 (m, 1 H), 6.43 (s, 1 H), 4.87 (s, 2 H), 3.70 (s, 3 H), 3.15 (s, 3 H); for minor rotomer δ 8.68 (s, 1 H), 8.47 (s, 2 H), 6.19 (s, 1 H), 5.10 (s, 2 H), 3.74 (s, 3 H), 3.01 (s, 3 H); MS (ES) m/e 346 (M + H)+.
  • 54
  • HOBt · H2O [ No CAS ]
  • trans-3-(3-pyridyl)acrylic acid [ No CAS ]
  • [ 3514-15-6 ]
  • (E)-N-Methyl-N-(1-methyl-1 H-indol-2-ylmethyl)-3-(pyridin-3-yl)acrylamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
40% With 1,2-dichloro-ethane In N,N-dimethyl-formamide 3 Preparation of (E)-N-Methyl-N-(1-methyl-1 H -indol-2-ylmethyl)-3-(pyridin-3-yl)acrylamide Example 3 Preparation of (E)-N-Methyl-N-(1-methyl-1 H -indol-2-ylmethyl)-3-(pyridin-3-yl)acrylamide EDC (0.22 g, 1.14 mmole) was added to a solution of trans-3-(3-pyridyl)acrylic acid (0.17 g, 1.14 mmole), 1-methyl-2-(methylaminomethyl)-1H-indole (0.20 g, 1.15 mmole), and HOBt · H2O (0.15 g, 1.11 mmole) in DMF (10 mL) at RT. The reaction was stirred overnight, then was concentrated in vacuo. The residue was diluted with 5% NaHCO3 and extracted with CH2Cl2. The combined organic extracts were washed with brine and dried over MgSO4. Flash chromatography on silica gel (3% MeOH/CH2Cl2) followed by preparative TLC (3% MeOH/CH2Cl2) gave the title compound (0.14 g, 40%) as a white solid: 1H NMR (360 MHz, CDCl3) indicated an approximately 8:1 mixture of amide rotamers; for the major rotamer: δ 8.79 (s, 1 H), 8.59 (d, J = 3.9 Hz, 1 H), 7.84 (d, J = 7.6 Hz, 1 H), 7.76 (d, J = 15.5 Hz, 1 H), 7.59 (d, J = 7.8 Hz, 1 H), 7.38 - 7.48 (m, 2 H), 7.19-7.27(m, 1 H), 7.08 - 7.17 (m, 1 H), 6.98 (d, J = 15.5 Hz, 1 H), 6.51 (s, 1 H), 4.94 (s, 2 H), 3.73 (s, 3 H), 3.09 (s, 3 H); MS (ES) m/e 306 (M + H)+. Anal. Calcd for C19H19N3O · 0.20 H2O: C, 73.86; H, 6.33; N, 13.60. Found: C, 73.52; H, 6.32; N, 13.43.
  • 55
  • HOBt · H2O [ No CAS ]
  • [ 3514-15-6 ]
  • [ 139223-62-4 ]
  • (E)-3-(4-aminophenyl)-N-methyl-N-(1-methyl-1 H-indol-2-ylmethyl)acrylamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
19% With 1,2-dichloro-ethane; triethylamine In N,N-dimethyl-formamide 2 Preparation of (E)-3-(4-aminophenyl)-N-methyl-N-(1-methyl-1 H -indol-2-ylmethyl)acrylamide Example 2 Preparation of (E)-3-(4-aminophenyl)-N-methyl-N-(1-methyl-1 H -indol-2-ylmethyl)acrylamide EDC (218 mg, 1.14 mmole) was added to a solution of 4-aminocinnamic acid hydrochloride (220 mg, 1.10 mmole), 1-methyl-2-(methylaminomethyl)-1H-indole (0.20 g, 1.15 mmole), HOBt · H2O (154 mg, 1.14 mmole), and triethylamine (0.20 mL, 1.43 mmole) in DMF (20 mL) at RT. The reaction was stirred overnight, then was concentrated in vacuo. The residue was diluted with 5% NaHCO3 and extracted with CH2Cl2. The combined organic extracts were washed with brine (2 x 30 mL) and dried over MgSO4. Flash chromatography on silica gel (3% MeOH/CH2Cl2) gave the title compound (68 mg, 19%) as a yellow foam: 1H NMR (360 MHz, DMSO-d6, 330K) δ 7.46 (d, J = 7.8 Hz, 1 H), 7.42 (d, J = 15.3 Hz, 1 H), 7.37 (d, J = 8.3 Hz, 1 H), 7.32 (d, J = 8.5 Hz, 2 H), 7.06 - 7.15 (m, 1 H), 6.94 - 7.03 (m, 1 H), 6.81 (d, J = 15.3 Hz, 1 H), 6.58 (d, J = 8.5 Hz, 2 H), 6.33 (s, 1 H), 5.25 (br s, 2 H), 4.85 (s, 2 H), 3.70 (s, 3 H), 3.02 (s, 3 H); MS (ES) m/e 320 (M + H)+. Anal. Calcd for C20H21N3O · 0.20 H2O: C, 74.37; H, 6.68; N, 13.01. Found: C, 74.21; H, 6.60; N, 12.80.
  • 56
  • conc. NH4OH [ No CAS ]
  • [ 61939-18-2 ]
  • [ 3514-15-6 ]
YieldReaction ConditionsOperation in experiment
93% With sodium hydroxide; LiAlH4 In tetrahydrofuran; methanol; water 1.c c c 1-Methyl-2-(methylaminomethyl)-1H-indole A 3-liter 3-necked roundbottom flask equipped with overhead stirring was charged with N,1-dimethyl-1H-indole-2-carboxamide (23.45 g, 124.58 mmole) and anhydrous THF (170 mL). The solution was stirred while a solution of LiAlH4 in THF (1.0 M, 250 mL, 250 mmole) was added via syringe. Gas was evolved during the addition of the first 50 mL of LiAlH4 solution. When the addition was complete, the resulting light yellow solution was heated at gentle reflux. After 23 hr, the reaction was cooled in ice and quenched by the sequential dropwise addition of H2O (9.5 mL), 15% NaOH (9.5 mL), and H2O (28.5 mL). The mixture was stirred for 15 min, then was filtered through celite(D, and the filter pad was washed thoroughly with THF. The filtrate was concentrated and the residue was flash chromatographed on silica gel (10% MeOH/CHCl3 containing 0.5% conc. NH4OH). The title compound (20.17 g, 93%) was obtained as a light yellow oil: 1H NMR (300 MHz, CDCl3) δ 7.56 (d, J=7.8 Hz, 1 H), 7.02-7.35 (m, 3H), 6.38 (s, 1 H), 3.88 (s, 2H), 3.75 (s, 3H), 2.49 (s, 3H).
  • 57
  • [ 5413-85-4 ]
  • [ 3514-15-6 ]
  • [ 1007197-98-9 ]
YieldReaction ConditionsOperation in experiment
74% With potassium carbonate In N,N-dimethyl-formamide
  • 58
  • C21H29N3O5 [ No CAS ]
  • [ 3514-15-6 ]
  • C32H41N5O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide
  • 62
  • [ 27421-51-8 ]
  • [ 74-89-5 ]
  • [ 3514-15-6 ]
YieldReaction ConditionsOperation in experiment
4 g Stage #1: 1-methyl-1H-indole-2-carboxaldehyde; methylamine In ethanol at 20℃; for 18h; Stage #2: With sodium tetrahydroborate In ethanol at 0 - 20℃; To a stirred solution of l-Methyl-lH-indole-2-carbaldehyde 1 (5g, 31.44 mmol) in ethanol, was added 40 % methyl amine solution (30ml). After stirring for 18h at room temperature, sodium borohydride (1.16g, 31.44 mmol ) was added at 0°C and the total reaction mixture was stirred at room temperature for 6h. Water was added and concentrated under vacuum. The crude material was partitioned between water and ethyl acetate. Organic layer was separated, dried over sodium sulphate and concentrated under vacuum to get the desired compound 2 (4 g)
4 g Stage #1: 1-methyl-1H-indole-2-carboxaldehyde; methylamine In ethanol at 20℃; for 18h; Stage #2: With sodium tetrahydroborate; ethanol at 0 - 20℃; for 6h; Synthesis of Intermediate A Step-1 [0025] To a stirred solution of 1-Methyl-1H-indole-2-carbaldehyde 1 (5 g, 31.44 mmol) in ethanol, was added 40% methyl amine solution (30 ml). After stirring for 18 h at room temperature, sodium borohydride (1.16 g, 31.44 mmol) was added at 0° C. and the total reaction mixture was stirred at room temperature for 6 h. Water was added and concentrated under vacuum. The crude material was partitioned between water and ethyl acetate. Organic layer was separated, dried over sodium sulphate and concentrated under vacuum to get the desired compound 2 (4 g)
  • 63
  • [ 3514-15-6 ]
  • [ 1428798-97-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / -78 °C 2: palladium diacetate; tris-(o-tolyl)phosphine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / Inert atmosphere; Reflux
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / -78 °C 2: palladium diacetate; tris-(o-tolyl)phosphine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / Inert atmosphere; Reflux
  • 64
  • [ 3514-15-6 ]
  • [ 1428799-00-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / -78 °C 2: palladium diacetate; tris-(o-tolyl)phosphine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / Reflux
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / -78 °C 2: palladium diacetate; tris-(o-tolyl)phosphine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / Reflux
  • 65
  • [ 3514-15-6 ]
  • [ 1428799-01-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / -78 °C 2: palladium diacetate; tris-(o-tolyl)phosphine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / Reflux
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / -78 °C 2: palladium diacetate; tris-(o-tolyl)phosphine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / Reflux
  • 66
  • [ 3514-15-6 ]
  • [ 1428799-02-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / -78 °C 2: palladium diacetate; tris-(o-tolyl)phosphine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / Reflux
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / -78 °C 2: palladium diacetate; tris-(o-tolyl)phosphine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / Reflux
  • 67
  • [ 3514-15-6 ]
  • [ 1428799-03-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 2 h / -78 °C 2: palladium diacetate; tris-(o-tolyl)phosphine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / Reflux 3: hydrogenchloride / methanol / 1 h / 20 °C
Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 2 h / -78 °C 2: palladium diacetate; tris-(o-tolyl)phosphine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / Reflux 3: hydrogenchloride / methanol / 1 h / 20 °C
  • 68
  • [ 3514-15-6 ]
  • [ 1428799-55-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / -78 °C 2: palladium diacetate; tris-(o-tolyl)phosphine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / Reflux
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / -78 °C 2: palladium diacetate; tris-(o-tolyl)phosphine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / Reflux
  • 69
  • [ 3514-15-6 ]
  • [ 1428799-04-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / -78 °C 2: palladium diacetate; tris-(o-tolyl)phosphine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / Reflux; Inert atmosphere
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / -78 °C 2: palladium diacetate; tris-(o-tolyl)phosphine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / Inert atmosphere; Reflux
  • 70
  • [ 3514-15-6 ]
  • [ 1428799-06-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / -78 °C 2: palladium diacetate; tris-(o-tolyl)phosphine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / Reflux; Inert atmosphere
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / -78 °C 2: palladium diacetate; tris-(o-tolyl)phosphine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / Reflux; Inert atmosphere
  • 71
  • [ 3514-15-6 ]
  • [ 1428799-08-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / -78 °C 2: palladium diacetate; tris-(o-tolyl)phosphine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / Reflux; Inert atmosphere
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / -78 °C 2: palladium diacetate; tris-(o-tolyl)phosphine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / Inert atmosphere; Reflux
  • 72
  • [ 3514-15-6 ]
  • [ 709651-96-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / -78 °C 2: palladium diacetate; tris-(o-tolyl)phosphine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / Reflux; Inert atmosphere
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / -78 °C 2: palladium diacetate; tris-(o-tolyl)phosphine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / Inert atmosphere; Reflux
  • 73
  • [ 3514-15-6 ]
  • [ 335027-77-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / -78 °C 2: palladium diacetate; tris-(o-tolyl)phosphine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / Reflux; Inert atmosphere
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / -78 °C 2: palladium diacetate; tris-(o-tolyl)phosphine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / Inert atmosphere; Reflux
  • 74
  • [ 3514-15-6 ]
  • [ 1428799-09-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / -78 °C 2: palladium diacetate; tris-(o-tolyl)phosphine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / Reflux; Inert atmosphere
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / -78 °C 2: palladium diacetate; tris-(o-tolyl)phosphine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / Inert atmosphere; Reflux
  • 75
  • [ 3514-15-6 ]
  • [ 1428799-13-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / -78 °C 2: palladium diacetate; tris-(o-tolyl)phosphine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / Reflux; Inert atmosphere
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / -78 °C 2: palladium diacetate; tris-(o-tolyl)phosphine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / Inert atmosphere; Reflux
  • 76
  • [ 3514-15-6 ]
  • [ 1428798-93-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / -78 °C 2: palladium diacetate; tris-(o-tolyl)phosphine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / Reflux
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / -78 °C 2: palladium diacetate; tris-(o-tolyl)phosphine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / Reflux
  • 77
  • [ 3514-15-6 ]
  • [ 1428798-94-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 2 h / -78 °C 2: palladium diacetate; tris-(o-tolyl)phosphine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 36 h / 100 °C / Inert atmosphere 3: trifluoroacetic acid / 0 - 20 °C
Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 2 h / -78 °C 2: palladium diacetate; tris-(o-tolyl)phosphine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 36 h / 100 °C / Inert atmosphere 3: trifluoroacetic acid / 5 h / 0 - 20 °C
  • 78
  • [ 3514-15-6 ]
  • [ 1428799-38-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / -78 °C 2: palladium diacetate; tris-(o-tolyl)phosphine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 36 h / 100 °C / Inert atmosphere
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / -78 °C 2: palladium diacetate; tris-(o-tolyl)phosphine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 36 h / 100 °C / Inert atmosphere
  • 79
  • [ 3514-15-6 ]
  • [ 1428798-95-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / -78 °C 2: palladium diacetate; tris-(o-tolyl)phosphine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / Reflux
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / -78 °C 2: palladium diacetate; tris-(o-tolyl)phosphine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / Reflux
  • 80
  • [ 3514-15-6 ]
  • [ 1428798-96-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / -78 °C 2: palladium diacetate; tris-(o-tolyl)phosphine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / Inert atmosphere; Reflux
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / -78 °C 2: palladium diacetate; tris-(o-tolyl)phosphine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / Inert atmosphere; Reflux
  • 81
  • [ 3514-15-6 ]
  • [ 1428799-90-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / -78 °C 2: palladium diacetate; tris-(o-tolyl)phosphine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / Inert atmosphere; Reflux
  • 82
  • [ 3514-15-6 ]
  • VT-02-00034a [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 2 h / -78 °C 2: palladium diacetate; tris-(o-tolyl)phosphine; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 16 h / Inert atmosphere; Reflux
  • 83
  • [ 3770-50-1 ]
  • [ 3514-15-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: tetrahydrofuran 2: methylamine 3: lithium aluminium tetrahydride / tetrahydrofuran
  • 84
  • [ 18450-24-3 ]
  • [ 3514-15-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: methylamine 2: lithium aluminium tetrahydride / tetrahydrofuran
Same Skeleton Products
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[ 3514-15-6 ]

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