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[ CAS No. 496-15-1 ] {[proInfo.proName]}

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Chemical Structure| 496-15-1
Chemical Structure| 496-15-1
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Product Details of [ 496-15-1 ]

CAS No. :496-15-1 MDL No. :MFCD00005705
Formula : C8H9N Boiling Point : -
Linear Structure Formula :- InChI Key :LPAGFVYQRIESJQ-UHFFFAOYSA-N
M.W : 119.16 Pubchem ID :10328
Synonyms :

Calculated chemistry of [ 496-15-1 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 9
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.25
Num. rotatable bonds : 0
Num. H-bond acceptors : 0.0
Num. H-bond donors : 1.0
Molar Refractivity : 41.53
TPSA : 12.03 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.66 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.57
Log Po/w (XLOGP3) : 1.93
Log Po/w (WLOGP) : 1.08
Log Po/w (MLOGP) : 1.75
Log Po/w (SILICOS-IT) : 2.3
Consensus Log Po/w : 1.73

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.29
Solubility : 0.614 mg/ml ; 0.00515 mol/l
Class : Soluble
Log S (Ali) : -1.81
Solubility : 1.86 mg/ml ; 0.0156 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -2.95
Solubility : 0.134 mg/ml ; 0.00112 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.07

Safety of [ 496-15-1 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338-P210 UN#:N/A
Hazard Statements:H302-H315-H319-H335-H227 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 496-15-1 ]

* 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 [ 496-15-1 ]

[ 496-15-1 ] Synthesis Path-Downstream   1~100

  • 1
  • [ 496-15-1 ]
  • [ 16078-30-1 ]
YieldReaction ConditionsOperation in experiment
85% With triethylamine; In dichloromethane; acetyl chloride; PREPARATION 4 1-Acetylindoline To a stirred solution of indoline (1.43 g, 12 mmol) in dry methylene chloride (30 ml) was added triethylamine (1.7 ml, 12.3 mmol). The resultant mixture was cooled in an ice-bath to approximately 5 C. followed by dropwise addition of acetyl chloride (1.77 ml, 12 mmol). After the addition was complete the ice-bath was removed and the mixture was stirred further at room temperature for 1 hour. The reaction mixture was poured onto crushed ice. A methylene chloride extract was separated, washed with brine (20 ml), dried (MgSO4) and evaporated under reduced pressure affording 1.65 g (85% yield) of the title compound as a white solid. 1 H NMR (CDCl3) delta=2.23 (s, 3H), 3.18 (t, J=6 Hz, 2H), 4.04 (t, J=6 Hz, 2H), 6.96 (t, J=4 Hz, 1H), 7.12-7.20 (m, 2H), 8.18 (d, J= 4 Hz, 1H).
85% With acetic anhydride; In water; acetic acid; EXAMPLE III To a solution of 11.9 g (0.1 m) of indoline in 50 ml of acetic acid there were added dropwise 10.2 g of acetic anhydride. The solution was heated for 15 minutes on a steam bath and 35 ml of water added to the hot solution. After cooling, acetylindoline crystallized out as white plates which were isolated and dried to give 13.7 g (85% yield).
72.4% by weight With acetic anhydride; In ethanol; To a 3-neck 500 ml round bottom flask containing 108.5 g (0.911 mol) indoline was added acetic anhydride at a rate such as to maintain a temperature below 25 C. After addition (one hour), the reddish sludge was poured into ice water, filtered and washed several times with water. It was allowed to dry overnight and recrystallized from 700 ml of ethanol and gave 116.6 g (72.4% by weight yield) of N-acetylindoline.
  • 2
  • [ 120-72-9 ]
  • [ 64-19-7 ]
  • [ 496-15-1 ]
  • [ 16078-30-1 ]
  • 4
  • [ 496-15-1 ]
  • [ 108-24-7 ]
  • [ 16078-30-1 ]
YieldReaction ConditionsOperation in experiment
96.15% In dichloromethane; at 50℃;Green chemistry; A) 16 g (0.13 mol) of indoline and 130 g of dichloromethane were charged into a reaction flask to obtain a reaction mixture C; B) 15 g (0.15 mol) of acetic anhydride was added dropwise to the mixture C, and the mixture was reacted at 50 C to obtain a mixture D; C) The mixture D recovery of dichloromethane solvent, the N-acetyl indoline products 20.81g, the yield of 96.15%, product liquid chromatography purity ? 99%;
at 0℃;Reflux; Step A: 1-Acetylindoline 23 ml of acetic anhydride are added dropwise to 5 g of indoline, whilst maintaining the temperature of the mixture at 0. The mixture is refluxed for 4 hours, with stirring, and is then evaporated under reduced pressure. Flash chromatography on silica gel (cyclohexane/AcOEt: 6/4 and then pure AcOEt) allows 6.4 g of the expected product to be isolated.
With sodium hydroxide; In 1,2-dichloro-ethane; at 0 - 20℃; for 12h; At room temperature, 200 ml of dichloroethane and 200 ml of aqueous sodium hydroxide solution were added to the reaction vessel, and then 50 g of porphyrin was added. The temperature was lowered to 0 C., and 45 g of acetic anhydride was added dropwise. After reacting at 20 C. for 12 hours, the layers were separated and the organic layer was washed with water. The organic layer was collected and dried. The filtrate was concentrated to dryness under reduced pressure to give Compound 2 as a gray solid.
  • 5
  • [ 496-15-1 ]
  • [ 131-91-9 ]
  • [ 159256-79-8 ]
YieldReaction ConditionsOperation in experiment
74% In ethanol; for 0.416667h;Inert atmosphere; Microwave irradiation; Under nitrogen protection, 2.5 g (14.4 mmol) of 1-nitroso-2-naphthol was added to the flask. 6.9g (57.6mmol) indoline, ethanol was added to complete dissolution, was stirred under a pressure of 30 volts microwave,The reaction was heated 220 mA current for 25 minutes, the reaction was stopped, cooled and evaporated under reduced pressure to give the crude indoline, column chromatography to remove excess indole(silica gel G, developing solvent, n-hexane:ethyl acetate 1:3 (v/v)) to give 3.1 g of 1-nitroso-4-indoline-2-naphthol in a yield of 74%.
  • 6
  • [ 496-15-1 ]
  • [ 4770-37-0 ]
  • [ 85926-99-4 ]
  • 8
  • [ 496-15-1 ]
  • [ 6279-86-3 ]
  • [ 84088-82-4 ]
YieldReaction ConditionsOperation in experiment
38% at 215℃; Indoline (9a) (1.6 mL, 12.9 mmol) was added dropwise with stirring to triethyl methanetricarboxylate (3.2 mL, 12.9mmol) heated to 215C, at such a rate that the temperature of the reaction mixture was maintained within ±5C of the initial temperature. The ethanol eliminated during the reaction was distilled through a suitable still-head. After adding all the indoline the reaction mixture was maintained at the same temperature for 10-15 min, after which it was cooled. The solid ester 5a was filtered off, washed with water, and dried. Yield 1.3 g (38%); mp 303.0 -304C LC-MS (M+1) 260.4 1H NMR (300 MHz, DMSO) delta 13.10 (s, 1H), 7.68 (d, J = 8.2 Hz, 1H), 7.52 (d, J = 7.1 Hz, 1H), 7.22 - 7.13 (m, 1H), 4.33 (q, J = 7.1 Hz, 2H), 4.26 - 4.16 (m, 2H), 3.37 (s, 1H), 3.32 (s, 1H), 1.31 (t, J = 7.1 Hz, 3H).
23% at 230℃; for 0.5h; Indoline (1.6 g, 13.4 mmol) and triethyl methane tricarboxylate (3.1 g, 13.4 mmol) were heated at 230 C. for 30 minutes.The resulting compound was crystallized in hexane to give ethyl 6-hydroxy-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-5-carboxylate (0.8 g, 23% Yield).
  • 9
  • [ 496-15-1 ]
  • [ 134221-52-6 ]
  • [ 202463-42-1 ]
  • 10
  • [ 496-15-1 ]
  • [ 62796-78-5 ]
  • [ 16078-30-1 ]
  • 11
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  • [ 108-24-7 ]
  • [ 16078-30-1 ]
  • [ 33632-27-8 ]
  • 1-acetyl-2,3-dihydro-7-nitroindole [ No CAS ]
  • 12
  • [ 496-15-1 ]
  • [ 1122-10-7 ]
  • [ 570431-82-2 ]
  • 13
  • [ 496-15-1 ]
  • [ 75-36-5 ]
  • [ 16078-30-1 ]
YieldReaction ConditionsOperation in experiment
100% With sodium hydrogencarbonate; In dichloromethane; Example 5 1-(2,3-Dihydro-indol-1-yl)-ethanone To a suspension of NaHCO3 (504 g, 6.0 mol) and 2,3-dihydro-1H-indole (60 g, 0.5 mol) in CH2Cl2 (600 mL) cooled in an ice-water bath, was added dropwise acetyl chloride (78.5 g, 1.0 mol). The mixture was stirred at room temperature for 2 h. The solid was filtered off and the filtrate was concentrated to give 1-(2,3-dihydro-indol-1-yl)-ethanone (82 g, 100%).
100% With sodium hydrogencarbonate; In dichloromethane; at 20℃; for 2h; To a suspension of NaHCO3 (504 g, 6.0 mol) and 2,3-dihydro-1H-indole (60 g, 0.5 mol) in CH2Cl2 (600 mL) cooled in an ice-water bath, was added dropwise acetyl chloride (78.5 g, 1.0 mol). The mixture was stirred at room temperature for 2 h. The solid was filtered off and the filtrate was concentrated to give 1-(2,3-dihydro-indol-1-yl)-ethanone (82 g, 100%).
100% With sodium hydrogencarbonate; In dichloromethane; at 20℃; for 2h; To a suspension of NaHCO3 (504 g, 6.0 mol) and 2,3-dihydro-1H-indole (60 g, 0.5 mol) in CH2Cl2 (600 mL) cooled in an ice-water bath, was added dropwise acetyl chloride (78.5 g, 1.0 mol). The mixture was stirred at room temperature for 2 h. The solid was filtered off and the filtrate was concentrated to give 1-(2,3-dihydro-indol-1-yl)-ethanone (82 g, 100%).
97.5% With triethylamine; In tetrahydrofuran; at 20℃; for 20h; PREPARATION 58; 1- (2, 3-Dihvdro-indol-1-vl)-ethanone; A solution of 11.2 mL (0.1 mol) of indoline (commercially available from Aldrich Chemical company) in THF (200mL) was treated with triethyl amine (15.33 mL, 0.11 mol) followed by dropwise addition of acetyl chloride (7.82 mL, 0.11 mol). The reaction was stirred at room temperature for 20 hours, quenched with water (50 mL) followed by concentration in vacuo. White solid was collected and washed with water. Yield : 15.7 g (97. 5%).'H NMR (400 MHz, DMSO-d6) 8 ppm 2.11 (s, 3 H) 3.09 (t, J=8.55 Hz, 2 H) 4.03 (m, 2 H) 6.95 (m, 1 H) 7.10 (s, 1 H) 7.19 (d, J=6. 84 Hz, 1 H) 8.01 (d, J=7. 82 Hz, 1 H).
93.2% To a solution of indoline (1, 20.0 g, 0.168 mol) dissolved in dichloromethane (193 mL) was added triethylamine (82 mL) via pouring and with stirring in air for 10 min at room temperature. Another solution of acetyl chloride (17.4g, 0.222 mol) in dichloromethane (129 mL) was added to the first solution slowly via pipet and maintained at 5 C for 15 minutes. The resulting solution was stirred 18 hours at room temperature and checked for completion by TLC with a mobile phase of 50% ethyl acetate/hexanes. The solution was diluted with deionized water and extracted with dichloromethane three times. The organic portion was washed once with deionized water, once with IN HC1, twice with deionized water, and once with brine. The organic portion was then dried over Na2S04 for 15 minutes. After drying, the resulting solution was concentrated by rotary evaporation to yield the desired N-acetyl indoline (2) as a light brown/orange solid (25.2 g, 93.2%).
85.68% With potassium carbonate; In 1,2-dichloro-ethane; at 0℃;Green chemistry; A) 16 g (0.13 mol) of indoline, 140 g of 1,2-dichloroethane and 18.56 g of anhydrous potassium carbonate were charged into a reaction flask to obtain a reaction mixture C;B) The mixture C was cooled to 0 C, 11 g (0.16 mol) of acetyl chloride was added dropwise to the mixture C, and the reaction was carried out at 0 C after completion of the addition.C) After recovering 1,2-dichloroethane from the mixture D, 18.55 g of N-acetylindoline product was obtained in a yield of 85.68% and the purity of the product was 98%
81% With triethylamine; In dichloromethane; at 0 - 10℃; for 1h; Weigh 132g Compound 1 (commercially available) was added to a 2L three-necked flask, and then 1L of methylene chloride and 167g of triethylamine were added thereto, cooled to 0 C, acetyl chloride (130g, 1.5eq) Keep the temperature below 10 C. After the reaction was continued dropwise lh.After completion of the reaction by TLC monitoring, the organic layer was washed with water (700 mL * 3) and dried over anhydrous sodium sulfate. The solvent was concentrated and recrystallized from ethanol to give 145 g of a yellow solid (Compound 2), JS m / z: 161 (M +). Yield: 81%.
With triethylamine; In dichloromethane; at 5 - 20℃; To a stirring solution of indoline (25 g, 210 mmol) in DCM (200 ml) was added TEA (102 ml, 734 mmol) at 5-10C followed by slow addition of acetyl chloride (19.69 ml, 277 mmol). Reaction mixture was stirred at RT for 4 h. The reaction mixture was diluted with water (100 ml) and aq. layer was extracted with DCM. Organic layer was separated and washed with water and brine. The organic layer was dried over Na2S04, filtered and concentrated under reduced pressure to afford crude product which was column purified (0-30% EtOAc in hexane) to get pure product.

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[2]Patent: US2011/98311,2011,A1
[3]Patent: US2012/309758,2012,A1 .Location in patent: Page/Page column 77
[4]Patent: US2015/231142,2015,A1 .Location in patent: Paragraph 0469
[5]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 4533 - 4537
[6]Journal of Organic Chemistry,2007,vol. 72,p. 9231 - 9239
[7]Patent: WO2005/66165,2005,A1 .Location in patent: Page/Page column 121-122
[8]Patent: WO2016/25637,2016,A1 .Location in patent: Paragraph 0099
[9]RSC Advances,2015,vol. 5,p. 23727 - 23736
[10]Journal of Organic Chemistry,2015,vol. 80,p. 1818 - 1827
[11]Advanced Synthesis and Catalysis,2015,vol. 357,p. 1149 - 1153
[12]Patent: CN106432040,2017,A .Location in patent: Paragraph 0125-0128
[13]Patent: CN104974072,2017,B .Location in patent: Paragraph 0108-0112
[14]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 5818 - 5821
[15]ACS Medicinal Chemistry Letters,2011,vol. 2,p. 780 - 785
[16]Chemistry - A European Journal,2014,vol. 20,p. 3606 - 3609
[17]Advanced Synthesis and Catalysis,2014,vol. 356,p. 929 - 933
[18]Chemical Communications,2014,vol. 50,p. 14249 - 14252
[19]Chemical Communications,2014,vol. 50,p. 14862 - 14865
[20]Organic and Biomolecular Chemistry,2016,vol. 14,p. 11244 - 11249
[21]Chemical Communications,2017,vol. 53,p. 11368 - 11371
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[23]Patent: WO2018/11747,2018,A1 .Location in patent: Page/Page column 39
[24]Chemical Communications,2018,vol. 54,p. 2494 - 2497
  • 14
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  • [ 118-12-7 ]
  • [ 1198-27-2 ]
  • [ 114747-44-3 ]
  • 15
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  • [ 80466-79-1 ]
  • [ 890169-38-7 ]
  • 16
  • [ 496-15-1 ]
  • [ 6914-71-2 ]
  • dimethyl 2-(2-(indolin-1-yl)ethyl)malonate [ No CAS ]
  • 17
  • [ 496-15-1 ]
  • [ 115093-90-8 ]
  • 5-chloro-4-(2,3-dihydro-indol-1-yl)-7<i>H</i>-pyrrolo[2,3-<i>d</i>]pyrimidine [ No CAS ]
  • 18
  • [ 401564-36-1 ]
  • [ 496-15-1 ]
  • 3-[(2S,4S)-1-tert-butoxycarbonyl-4-(1-indolinyl)-2-pyrrolidinylcarbonyl]-1,3-thiazolidine [ No CAS ]
  • 19
  • [ 496-15-1 ]
  • [ 890315-72-7 ]
  • [ 910240-99-2 ]
YieldReaction ConditionsOperation in experiment
With caesium carbonate; XPhos;palladium diacetate; tris-(dibenzylideneacetone)dipalladium(0); In toluene; at 20℃; for 6.5h;Heating / reflux; To toluene 30mL solution of <strong>[890315-72-7]tert-butyl 4-bromo-2-nitrobenzoate</strong> 3.0g were added indoline 2.1mL, cesium carbonate 8.0g, 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl 0.29g, tris(dibenzylideneacetone)dipalladium(0) 0.11g and palladium acetate 55mg at room temperature, and it was heated and refluxed under nitrogen atmosphere for 3 hours and 30 minutes. After the reaction mixture was cooled to room temperature, 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl 0.29g, tris(dibenzylideneacetone)dipalladium(0) 0.11g and palladium acetate 55mg were added to it, and it was heated and refluxed under nitrogen atmosphere for 3 hours. After the reaction mixture was cooled to room temperature, ethyl acetate and 10% citric acid aqueous solution were added to it. The organic layer was separated and collected, dried over anhydrous magnesium sulfate after washing with saturated sodium chloride aqueous solution, and the solvent was removed under reduced pressure. Toluene was added to the obtained residue, dried over anhydrous magnesium sulfate after sequential washing with 1.0mol/L hydrochloric acid and saturated sodium chloride aqueous solution, and the solvent was removed under reduced pressure. The obtained residue was refined by silica gel column chromatography [Fuji SILYSIA Chemical Ltd., PSQ100B(spherical type), eluent; hexane:ethyl acetate=10:1] to give tert-butyl 4-(indolin-1-yl)-2-nitrobenzoate 2.0g of yellow solid. 1H-NMR(DMSO-d6) delta value: 1.48(9H,s),3.15(2H,t,J=8.4Hz),4.04(2H,t,J=8.4Hz),6.91(1 H,t,J=7.4Hz),7.17(1H,t,J=7.4Hz),7.25-7.30(1H,m),7.35(1H,d,J=8.0Hz),7.50-7.55(2H,m),7.81(1H,d,J=8.6Hz)
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  • [ 118511-81-2 ]
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  • [ 15121-84-3 ]
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  • [ 1670-83-3 ]
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  • [ 496-15-1 ]
  • [ 53330-94-2 ]
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  • [ 143262-17-3 ]
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  • [ 143262-20-8 ]
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  • [ 21640-48-2 ]
  • [ 496-15-1 ]
  • 31
  • [ 52537-00-5 ]
  • [ 496-15-1 ]
YieldReaction ConditionsOperation in experiment
39% With sodium cyanoborohydride; In acetic acid; for 10h; Sodium cyanoborohydride (4. [88] g, 77.8 mmol) was added to a solution of 6- chloroindoline (5.9 g, [38.] 9 mmol) in acetic acid (100 mL). Gas evolution was evident at the beginning of the reaction. After stirring for 10 h, the solution was diluted with water (100 mL) and 6 N [NAOH] was added until the pH of the reaction mixture was 12-13. The resulting mixture was extracted with [CH2CLZ] (3 x 200 mL), and the combined organic layers dried over [MGS04.] Flash column chromatography on silica gel (35% [ETOAC/HEXANES)] yielded 2.3 g (39%) of a clear liquid : 1H NMR (DMSO-d6) 8 2.87 (t, J= 8.4 Hz, 2H), 3.44 (t, [J =] 8.4 Hz, 2H), 6.45 (d, J= 1.8 Hz, 1H), 6.47 (dd, J = 1.8, 7.6 Hz, 1H), 6.96 (d, J = 7.3 Hz, 1H).
  • 32
  • [ 496-15-1 ]
  • [ 10130-89-9 ]
  • [ 485769-38-8 ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In methanol; at 0 - 20℃; for 5h; A chilled solution of indoline (3.22 g, 27.0 mmol, Aldrich) and triethylamine (3.0 mL, 22 mmol) in methanol (10 mL) was added by cannula to solid 4-(chlorosulfonyl)benzoic acid (4.04 g, 18.3 mmol, Aldrich) with stirring in an ice bath.The ice bath was removed after 30 minutes, and the mixture was stirred at room temperature for an additional 4.5 hours. The mixture was added to a separatory funnel with 90 mL of 1 M aqueous [NAOH,] and this solution was washed with 2 X 75 mL of [CH2C12.] The aqueous layer was then acidified with concentrated HC1. The resulting precipitate was collected, washed with water, and recrystallized from hot ethanol. The crystals were collected, washed with pentane, and dried at [120 C] under vacuum.Yield was 4.6 g of yellow-brown crystalline solid.
  • 33
  • [ 496-15-1 ]
  • [ 32161-06-1 ]
  • 1-(1-acetylpiperidin-4-yl)indoline [ No CAS ]
YieldReaction ConditionsOperation in experiment
82.2% With sodium hydroxide;palladium-carbon; In methanol; acetic acid; (87-1) 1-(1-Acetylpiperidin-4-yl)indoline Indoline (25 ml), 1-acetyl-4-piperidone (25 g) and glacial acetic acid (20 ml) were dissolved in methanol (300 ml). After adding 10% palladium carbon (1.0 g) thereto, catalytic reduction was carried out under atmospheric pressure. After the completion of the reaction, the reaction solution was filtered through celite, washed with methanol and concentrated under reduced pressure. The residue was partitioned between water and ethyl acetate and basif ied with a 5 N aqueous solution of sodium hydroxide followed by extraction with ethyl acetate. The ethyl acetate layer was washed with water and brine, dried and concentrated under reduced pressure. The resulting residue was purif ied by silica gel column chromatography (ethyl acetate/hexane system) to give the title compound (35.6 g) as a pale yellow wax (yield: 82.2%). 1H-NMR (400 MHz, CDCl3): delta(ppm) 1.50-1.62(2H, m), 1.81-1.93(2H, m), 2.12(3H, s), 2.59(1H, br-t), 2.96(2H, t, J=7.2Hz), 3.15(1H, br-t), 3.31-3.39(2H, m), 3.57-3.64(1H, m), 3.93(1H, br-d), 4.78(1H, br-d), 6.42(1H, d, J=8.0Hz), 6.62(1H, t, J=8.0Hz), 7.02-7.09(2H, m).
  • 34
  • [ 496-15-1 ]
  • [ 1749-68-4 ]
  • 6-amino-4-(1-indolinyl)-2-methylpyrimidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
The 6-amino-4-(1-indolinyl)-2-methylpyrimidine was obtained as a solid, m.p. 209-210 C., in a similar number to that described for the analogous intermediate in Example 51 by reaction of 6-amino-4-chloro-2-methylpyrimidine with indoline.
  • 35
  • [ 496-15-1 ]
  • methanolic sodium methanolate [ No CAS ]
  • [ 545-06-2 ]
  • [ 115661-82-0 ]
YieldReaction ConditionsOperation in experiment
60.5% With BCl3; In methanol; hexane; pentan-1-ol; water; toluene; (a) Production of 7-cyanoindoline 22 g of BCl3 (187.8 mmol) in 120 ml of toluene (dried) was dissolved in a 750 ml round flask at -20. 15.9 g of indoline (133.4 mmol) in 100 ml of toluene was added within 25 minutes and the temperature rose to 10. This suspension was refluxed for 1 hour, then 110 ml of toluene was distilled off and the reaction mixture was cooled to 55 C. Then 38.4 g of trichloroacetonitrile (266 mmol) was added within 20 minutes and the resulting red solution was stirred for 20 hours at 60 C. After addition of methanol (110 ml) the reaction mixture was mixed within 1.5 hours with 60 g of a 30 percent methanolic sodium methanolate solution. After 1 hour of stirring the methanol was distilled off in a vacuum and then toluene (300 ml) and water (300 ml) were added. The aqueous phase was extracted several times with 200 ml of toluene. The combined toluene extracts were then washed with a 0.12N HCl (91 ml) and with water to remove the not reacted indoline. After concentration by evaporation of toluene 20.12 g of a brownish oil was obtained. The latter was then recrystallized in a hexane/pentanol mixture (80 ml; mixture ratio of hexane: pentanol=9:7) to obtain 11.47 g of a light brownish product with a purity of 99.4 percent corresponding to a yield of 60.5 percent relative to feedstock used. Other data concerning the product was: 1 H-NMR (CDCl3) delta in ppm: 3.08, t; 3.70, t; 4.53 bs, 6.61, t; 7.13, d; 7.18, d.
  • 36
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  • [ 131-91-9 ]
  • [ 114747-44-3 ]
YieldReaction ConditionsOperation in experiment
10% In Trichloroethylene; acetone; COMPARATIVE EXAMPLE 1 1,3-Dihydro-1,3,3-trimethyl-6'-(2,3-dihydroindol-1-yl) spiro[2H-indole-2,3'-3H-naphtho[2,1-b][1,4]oxazine] A mixture of 1-nitroso-2-naphthol (17.3 g; 0.10 mol) and indoline (23.8 g; 0.20 mol) in trichloroethylene (150 ml) was heated under reflux for 10 min. A solution of 1,3-dihydro-1,3,3-trimethyl-2-methyleneindoline (17.3 g; 0.1 mol) in trichloroethylene (100 ml) was added in one batch and the resulting mixture heated under reflux for 1 h. The solution was evaporatedand the oily residue treated with acetone to yield 1,3-Dihydro-1,3,3-trimethyl-6'-(2,3-dihydroindol-1-yl)spiro [2H-indole-2,3'-3H-naphtho[2,1-b][1,4]oxazine] as a yellow solid (4.44 g; 10%). m.p 255-7 C. STR10
  • 37
  • [ 1122-58-3 ]
  • [ 496-15-1 ]
  • [ 16078-30-1 ]
YieldReaction ConditionsOperation in experiment
With acetic anhydride; triethylamine; In chloroform; water; A 1-Acetylindoline A solution of 11.9 g of indoline in 100 ml of chloroform is cooled to 0 C., 13.9 ml of triethylamine are added and a solution of 10.4 ml of acetic anhydride in 10 ml of chloroform is then added dropwise, followed by 0.1 g of 4-dimethylaminopyride. After stirring for two hours at RT, water is added to the reaction mixture, extraction is carried out with chloroform, the organic phase is dried over sodium sulfate and the solvent is evaporated off under vacuum to give 15.44 g of the expected product, which is used as such.
  • 38
  • [ 496-15-1 ]
  • [ 769-54-0 ]
  • 2,3-Dihydro-1-(4-nitro-3-pyridinyl)-1H-indole [ No CAS ]
YieldReaction ConditionsOperation in experiment
In ethanol; EXAMPLE 1 2,3-Dihydro-1-(4-nitro-3-pyridinyl)-1H-indole, N-oxide A solution of 3-fluoro-4-nitropyridein-N-oxide1 (5 g) and indoline (4 g) in 100 ml ethanol was stirred for one hour at reflux and thereafter cooled and concentrated. The residue was purified by flash chromatography (silca, ethyl actate) to give 8 g solid, m.p. 168-170. Four grams were recrystallized from ethanol to give 3 g needles, m.p. 170-172.
  • 39
  • [ 496-15-1 ]
  • [ 545-06-2 ]
  • [ 115661-82-0 ]
YieldReaction ConditionsOperation in experiment
58% With boron trichloride; potassium carbonate; In methanol; dichloromethane; toluene; EXAMPLE 73 To a solution of 1.19 g of indoline in 10 ml of toluene was added 5.5 ml of a solution of 2.02M of boron trichloride in toluene under ice-cooling, and the mixture was refluxed on an oil bath for 1 hr. and evaporated under atmospheric pressure to remove the solvent. The residue was mixed with 2 ml of trichloroacetonitrile and heated at 60-62 C. on an oil bath for 20 hr. The product was dissolved in 20 ml of methylene chloride and poured into a mixture of 9.1 g of potassium carbonate and 40 ml of methanol under ice-cooling. The mixture was refluxed on an oil bath for 1 hr. and filtered to remove the insoluble material. The filtrate was evaporated and partitioned between water and methylene chloride. The methylene chloride layer was washed with dilute HCl, dried over anhydrous magnesium sulfate and evaporated to dry- ness. The residue (1.10 g) was purified on a Lobar column and the product (0.913 g) from the methylene chloride elude was recrystallized from ether-hexane to give 0.836 g of 7-cyanoindoline as crystals melting at 66-67 C. Yield: 58% Anal Calcd (%) for C9 H8 N2: C, 74.97; H, 5.59; N, 19.43; Found (%): C, 74.98; H, 5.60; N, 19.51. IR (CHCl3): 3432, 2217 cm-1.
  • 40
  • [ 496-15-1 ]
  • [ 53554-29-3 ]
  • [ 334703-29-6 ]
YieldReaction ConditionsOperation in experiment
77% In ethanol; Reference Example 2-1 ethyl 4-hydroxy-2-(2,3-dihydro-1H-indol-1-yl)-5-pyrimidinecarboxylate To a solution of indoline (3.58 g, 30 mmol) in ethanol (50 mL) was added <strong>[53554-29-3]ethyl 2-methylthio-4-hydroxypyrimidine-5-carboxylate</strong> (5.35 g, 25 mmol) and the mixture was heated under reflux for 18 h. The reaction mixture was allowed to cool to room temperature and the precipitated crystals were collected by filtration. The crystals were washed several times with cold ethanol and dried to give the title compound (5.5 g, 77%) as crystals.
  • 41
  • [ 496-15-1 ]
  • [ 890315-75-0 ]
  • [ 564483-18-7 ]
  • tert-butyl 2-(benzamido)-4-(indolin-1-yl)benzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With caesium carbonate; citric acid;tris-(dibenzylideneacetone)dipalladium(0); palladium diacetate; In ethyl acetate; toluene; Example 253 0.031 mL of indoline, 0.12 g of cesium carbonate, 1.7 mg of tris(dibenzylideneacetone)dipalladium(0), 0.8 mg of palladium acetate and 4.4 mg of 2-dicyclohexylphosphino -2',4',6'-triisopropylbiphenyl were added to 1.4 mL of toluene solution containing 70 mg of tert-butyl 2-(benzamido)-4-bromobenzoate at room temperature, and the resulting mixture was heated to reflux under nitrogen atmosphere for 3 hours. After the reaction mixture was cooled to room temperature, ethyl acetate and 10% citric acid aqueous solution were added and insoluble were removed by filtration. The organic layer was separated and dried over anhydrous magnesium sulfate after washed with a saturated sodium chloride aqueous solution, and the solvent was evaporated under reduced pressure. The obtained residue was purified with silica gel column chromatography [PSQ100B (spherical) manufactured by Fuji Silysia Chemical Ltd., eluent; hexane: ethyl acetate = 10:1] to obtain 77 mg of tert-butyl 2-(benzamido)-4-(indolin-1-yl)benzoate as yellow oil. 1H-NMR (CDCl3) delta: 1.63 (9H, s), 3. 17 (2H, t, J = 8.4 Hz), 4.10 (2H, t, J = 8.4 Hz), 6.86 (1H, td, J = 7.4, 0.8 Hz), 6.96 (1H, dd, J = 8.9, 2.5 Hz), 7.16-7.24 (2H, m), 7.46-7.57 (4H, m), 7.97 (1H, d, J = 8.9 Hz), 8.06-8.10 (2H, m), 8.81 (1H, d, J = 2.5 Hz), 12.40 (1H, s).
  • 42
  • [ 496-15-1 ]
  • [ 10111-08-7 ]
  • [ 1022886-77-6 ]
YieldReaction ConditionsOperation in experiment
52% With sodium cyanoborohydride; zinc(II) chloride; In methanol; at 50℃; for 16h; Example 1 1-(1H-Imidazol-2-ylmethyl)-2,3-dihydro-1H-indole To a solution of indoline (0.20 g, 1.68 mmol) in methanol (15 ml) were added sequentially imidazole-2-carboxaldehyde (0.24 g, 2.52 mmol), zinc chloride (0.92 g, 6.71 mmol) and sodium cyanoborohydride (0.32 g, 5.03 mmol). The reaction mixture was shaken at 50 C. for 16 hours, then triethylamine (0.5 ml) was added and the mixture shaken for a further 5 min. The resulting suspension was filtered and the filtrate was concentrated in vacuo. The residue was purified by chromatography on silica gel (eluant: methanol/dichloromethane gradient) to yield the title compound as an off-white solid (0.17 g, 52%); MS (ISP): 200.3 ([M+H]+).
  • 43
  • [ 496-15-1 ]
  • [ 26496-94-6 ]
  • [ 1187212-20-9 ]
YieldReaction ConditionsOperation in experiment
43.18% With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 8h; To a stirred solution of indoline (1.5g , 12.58 mmol) in dry DMF (50 ml), potassium carbonate (3.47g , 25.17 mmol) and 4-bromomethyl ethyl benzoate (3.05 g , 13.84 mmol) was added and reaction mixture was heated at 60 0C for 8 h. The reaction mixture was cooled to room temperature and then water (40 ml) was added and extracted with ethyl acetate (3x25 ml). The combined extracts was dried over anhydrous sodium sulfate and concentrated in vacuo. Product was purified by silica gel column using 2% ethyl acetate in hexane as a eluent to afford brown liquid (1.52 g, 43.18 %).
  • 44
  • [ 496-15-1 ]
  • [ 6627-78-7 ]
  • [ 1203581-68-3 ]
  • 45
  • [ 496-15-1 ]
  • [ 621-38-5 ]
  • [ 1203581-79-6 ]
  • 46
  • [ 496-15-1 ]
  • [ 62005-48-5 ]
  • [ 1216928-43-6 ]
  • 47
  • [ 496-15-1 ]
  • [ 7755-70-6 ]
  • [ 841214-40-2 ]
  • 48
  • [ 496-15-1 ]
  • [ 50910-55-9 ]
  • [ 1265521-33-2 ]
  • 50
  • [ 496-15-1 ]
  • [ 5470-22-4 ]
  • [ 1090397-77-5 ]
YieldReaction ConditionsOperation in experiment
52% With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; triethylamine; In tetrahydrofuran; at 20℃; for 3h; (4-chloropyridin-2-yl)-(2,3-dihydroindol-1-yl)-methanone 800 muL (7.07 mmol) 2,3-dihydro-1H-indole were added to 1.0 g (6.35 mmol) <strong>[5470-22-4]4-chloropyridine-2-carboxylic acid</strong>, 1.0 mL (7.12 mmol) triethylamine and 2.20 g (6.85 mmol) TBTU in 100 mL THF. The reaction mixture was stirred for 3 h at RT, diluted with ethyl acetate (100 mL) and washed with 15% potassium carbonate solution (2*50 mL), saturated sodium chloride solution (1*50 mL) and 1M hydrochloric acid (2*30 mL). The organic phase was dried on magnesium sulphate, filtered and evaporated down i. vac. Yield: 850 mg (52% of theory) ESI-MS: 259/261 (M+H)+
  • 51
  • [ 496-15-1 ]
  • 2-oxo-1-(4-piperidinyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine dihydrochloride [ No CAS ]
  • [ 166526-03-0 ]
  • [ 201230-82-2 ]
  • [ 1159008-94-2 ]
  • [ 1159008-95-3 ]
YieldReaction ConditionsOperation in experiment
Intermediate 60Isomer mixture of 5'-cyano-4-(2-oxo-2,3-dihydro-imidazo[4,5-b]pyridin-1-yl)-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4'-carboxylic acid and 5'-cyano-4-(2-oxo-2,3-dihydro-imidazo[4,5-b]pyridin-1-yl)-3,4,5,6-tetrahydro-2H-[1,4']bipyridinyl-2'-carboxylic acid Step 1: Isomer mixture of 4'-chloro-4-(2-oxo-2,3-dihydro-imidazo[4,5-b]pyridin-1-yl)-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-5'-carbonitrile and 6'-chloro-4-(2-oxo-2,3-dihydro-imidazo[4,5-b]pyridin-1-yl)-3,4,5,6-tetrahydro-2H-[1,4']bipyridinyl-3'-carbonitrile 1.50 g (5.15 mmol) 1-piperidin-4-yl-1,3-dihydroimidazo[4,5-b]pyridin-2-one-dihydrochloride and 3.59 mL (20.6 mmol) DIPEA were placed in 45 mL ethanol. 891 mg (5.00 mmol) <strong>[166526-03-0]4,6-dichloro-nicotinonitrile</strong> and 3 spatula tips of DMAP were added and the reaction mixture was stirred for 4 h at RT. The precipitated solid was suction filtered, washed with ethanol and dried.Yield: 1.41 g (77% of theory)ESI-MS: m/z=355/357 (Cl) (M+H)+ Rt (HPLC-MS): 1.15 min (method C)Step 2 Isomer mixture of methyl 5'-cyano-4-(2-oxo-2,3-dihydro-imidazo[4,5-b]pyridin-1-yl)-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4'-carboxylate and methyl 5'-cyano-4-(2-oxo-2,3-dihydro-imidazo[4,5-b]pyridin-1-yl)-3,4,5,6-tetrahydro-2H-[1,4']bipyridinyl-2'-carboxylate In a CO atmosphere 717 mg (2.02 mmol) of an isomer mixture of 4'-chloro-4-(2-oxo-2,3-dihydro-imidazo[4,5-b]pyridin-1-yl)-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-5'-carbonitrile and 6'-chloro-4-(2-oxo-2,3-dihydro-imidazo[4,5-b]pyridin-1-yl)-3,4,5,6-tetrahydro-2H-[1,4']bipyridinyl-3'-carbonitrile, 78 mg (0.20 mmol) PdCl2(PhCN)2, 112 mg (0.20 mmol) dppf and 0.34 mL (2.4 mmol) TEA in 30 mL methanol were carbonylated for 4 h at 130 C. and 25 bar. The catalyst was removed by suction filtering and the filtrate was concentrated to dryness by rotary evaporation. The residue was combined with isopropanol and the precipitated solid was suction filtered and dried.Yield: 112 mg (15% of theory)Rt (HPLC-MS): 1.05 min (method C) Step 3 Isomer mixture of 5'-cyano-4-(2-oxo-2,3-dihydro-imidazo[4,5-b]pyridin-1-yl)-3,4,5,6-tetrahydro-2H-[1,2']-bipyridinyl-4'-carboxylic acid and 5'-cyano-4-(2-oxo-2,3-dihydro-imidazo[4,5-b]pyridin-1-yl)-3,4,5,6-tetrahydro-2H-[1,4']bipyridinyl-2'-carboxylic acid 272 mg (0.720 mmol) of an isomer mixture of methyl 5'-cyano-4-(2-oxo-2,3-dihydro-imidazo[4,5-b]pyridin-1-yl)-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4'-carboxylate and methyl 5'-cyano-4-(2-oxo-2,3-dihydro-imidazo[4,5-b]pyridin-1-yl)-3,4,5,6-tetrahydro-2H-[1,4']bipyridinyl-2'-carboxylate were stirred overnight in 4.0 mL THF, 0.54 mL (2.1 mmol) of a 4M NaOH solution and 0.54 mL water at RT. The organic solvent was eliminated by rotary evaporation and the aqueous phase was combined with 50 mL water and 25 mL of a 4M HCl solution. The reaction mixture was stirred for one hour at RT, then the precipitated solid was suction filtered and dried.Yield: 210 mg (80% of theory)ESI-MS: m/z=365 (M+H)+ Rt (HPLC-MS): 3.65 min (method C) Example 174 6'-(2,3-dihydro-indole-1-carbonyl)-4-(2-oxo-2,3-dihydro-imidazo[4,5-b]pyridin-1-yl)-3,4,5,6-tetrahydro-2H-[1,4']bipyridinyl-3'-carbonitrile 0.11 mg (0.29 mmol) of an isomer mixture of 5'-cyano-4-(2-oxo-2,3-dihydro-imidazo[4,5-b]pyridin-1-yl)-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4'-carboxylic acid and 5'-cyano-4-(2-oxo-2,3-dihydro-imidazo[4,5-b]pyridin-1-yl)-3,4,5,6-tetrahydro-2H-[1,4']bipyridinyl-2'-carboxylic acid, 34 mg (0.29 mmol) 2,3-dihydro-1H-indole and 90 muL (0.61 mmol) TEA were placed in 1.5 mL DMF. 0.10 g (0.32 mmol) TBTU were added. The reaction mixture was stirred over the weekend at RT. The purification and separation of the isomers were carried out by HPLC-MS. The product-containing fractions were combined and freeze-dried. Yield: 18 mg (13% of theory) ESI-MS: m/z=466 (M+H)+Example 175 4'-(2,3-dihydro-indole-1-carbonyl)-4-(2-oxo-2,3-dihydro-imidazo[4,5-b]-pyridin-1-yl)-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-5'-carbonitrile This compound was obtained as described for 6'-(2,3-dihydro-indole-1-carbonyl)-4-(2-oxo-2,3-dihydro-imidazo[4,5-b]pyridin-1-yl)-3,4,5,6-tetrahydro-2H-[1,4']bipyridinyl-3'-carbonitrile. Yield: 5 mg (4% of theory) ESI-MS: m/z=466 (M+H)+
  • 52
  • [ 496-15-1 ]
  • [ 939-18-4 ]
  • [ 1335032-89-7 ]
  • 53
  • [ 496-15-1 ]
  • [ 161596-47-0 ]
  • [ 1357474-56-6 ]
  • 54
  • [ 496-15-1 ]
  • [ 60230-36-6 ]
  • [ 1374155-11-9 ]
  • 55
  • [ 496-15-1 ]
  • [ 701-27-9 ]
  • [ 893902-38-0 ]
YieldReaction ConditionsOperation in experiment
100% With pyridine; at 20℃; Example 27Synthesis of 5-((2,3-dihydrobenzo[alpha][1,4]dioxin-6-yl)sulfonyl)-1-((3-fluorophenyl)sulfonyl)indolineReagents Table MW Reagent/raw material (gr/mole) Quantity moles Indoline 119.16 130 g 1.1 mmol 3-fluorobenzene-1-sulfonyl 194.61 0.3 g 1.5 mmol chloride 1-((3- 277.31 0.327 g 1.18 mmol fluorophenyl)sulfonyl)indoline 2,3- 234.66 0.33 g 1.41 mmol dihydrobenzo[b][1,4]dioxine- 6-sulfonyl chloride Aluminium chloride 133.3 0.47 3.5 mmol Procedure:Synthesis of 1: Indoline was dissolved in 5 ml dry pyridine, and <strong>[701-27-9]3-fluorobenzene-1-sulfonyl chloride</strong> was added. Reaction stirred for overnight at RT, intense red color developed. When complete by HPLC and LCMS, solvent was evaporated, crude reaction mixture was dissolved in EA and washed with HCl 1N, water and brine. Organic phase was evaporated and purified by CombiFlash (PE/EtOAC) yield 0.325 g product 100% pure, (100%% yield)
In pyridine; at 20℃; for 20h; General procedure: 2-Methylindoline (400 mg, 3.0 mmol, 1.0 equiv) was dissolved in dry pyridine (10 mL). Methane sulfonyl chloride (480 mg, 4.2 mmol, 1.4 equiv) was added dropwise and the reaction mixture was stirred overnight at rt. Monitoring by HPLC and LCMS indicated that the reaction was completed. The solvent was evaporated under reduced pressure. A solution of HCl 1N (50 mL) and EtOAc (50 mL) were added. The organic layer was separated and the aqueous phase was extracted twice with EtOAc (2x50 mL). The combined organic phase was dried over Na2SO4 and the solvent was evaporated under reduced pressure to yield the pure product: 634 mg, 100 % yield.
  • 56
  • [ 496-15-1 ]
  • [ 60230-36-6 ]
  • [ 1004219-87-7 ]
YieldReaction ConditionsOperation in experiment
89% With pyridine; at 20℃; Example 28Synthesis of 1-((2,6-difluorophenyl)sulfonyl)-5-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)sulfonyl)indolineReagents Table-Step 1 MW Quantity/ Mole Reagent/raw material (gr/mole) mgr Mmole ratio Indoline 119.2 0.19 ml 1.7 1.0 2,6-Difluorobenzene-1-sulfonyl 212.6 510 2.4 1.4 chloride Pyridine - 10 ml - - Procedure:Indoline was dissolved in dry pyridine. 2,6-Difluorobenzene-1-sulfonyl chloride was added dropwise and the reaction mixture was stirred overnight at rt. Intense red color appeared during the reaction. Monitoring by HPLC and LCMS indicated that the reaction was completed. The solvent was evaporated under reduced pressure, then HCl 1N solution and EtOAc were added. The organic layer was separated and the aqueous phase was extracted twice with EtOAc. The combined organic phase was dried over Na2SO4 and the solvent was evaporated under reduced pressure to yield the pure product as a yellow solid: 450 mg, 89percent yield.
  • 57
  • [ 16078-30-1 ]
  • [ 496-15-1 ]
  • [ 5876-09-5 ]
  • [ 64-17-5 ]
  • 58
  • [ 496-15-1 ]
  • [ 1065181-58-9 ]
  • 59
  • [ 496-15-1 ]
  • [ 3032-81-3 ]
  • [ 1416164-16-3 ]
  • [ 1416164-52-7 ]
  • 60
  • [ 496-15-1 ]
  • [ 73583-39-8 ]
  • [ 1416164-16-3 ]
  • [ 1416164-54-9 ]
  • 61
  • [ 496-15-1 ]
  • [ 239463-85-5 ]
  • 5-[(2S)-2-aminopropyl]-2,3-dihydro-1-[3-(benzoyloxy)propyl]-1H-indole-7-carbonitrile L-(+)-tartrate [ No CAS ]
  • 62
  • [ 496-15-1 ]
  • [ 5424-47-5 ]
  • [ 1267977-01-4 ]
  • 63
  • [ 496-15-1 ]
  • [ 4489-34-3 ]
  • [ 1450821-81-4 ]
  • 64
  • [ 496-15-1 ]
  • [ 445-28-3 ]
  • C15H14N2O [ No CAS ]
  • 65
  • [ 496-15-1 ]
  • [ 631912-19-1 ]
  • 1-(3-bromo-4-fluorophenylsulfonyl)indoline [ No CAS ]
YieldReaction ConditionsOperation in experiment
67% With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 20℃; for 20.0h; Example 97A 1-(3-bromo-4-fluorophenylsulfonyl)indoline [1059] A mixture of <strong>[631912-19-1]3-bromo-4-fluorobenzene-1-sulfonyl chloride</strong> (2.53 g, 8.33 mmol), indoline (0.933 mL, 8.33 mmol), and N,N-diisopropylethyl-amine (1.60 mL, 9.16 mmol) in tetrahydrofuran (20 mL) was stirred at room temperature for 20 hours. The reaction mixture was partitioned between water and ether. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered, and concentrated to a solid residue. Recrystallization from ether and heptane provided the title compound (1.99 g, 67%).
  • 66
  • [ 496-15-1 ]
  • [ 15897-81-1 ]
  • [ 1422444-15-2 ]
YieldReaction ConditionsOperation in experiment
30% With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; Example 37 Adamantan-2-yl-(2,3-dihydro-indol-l-yl)-methanone A mixture of 24.2 mg (0.134 mmol) <strong>[15897-81-1]adamantane-2-carboxylic acid</strong>, 20 mg (0.168 mmol) indoline, 64.7 mg (0.2 mmol) TBTU and 43.4 mg (0.336 mmol) DIPEA in 1 mL DMF was stirred at room temperature overnight. Formic acid was added and the mixture was subjected to column chromatography on reversed phase eluting with a gradient formed from acetonitrile, water and NEt3 to yield after evaporation of the product containing fractions 14.1 mg (30 %) of the title compound. MS(m/e): 282.4 (MFT).
30% With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; Example 37 Adamantan-2-yl-(2,3-dihydro-indol-1-yl)-methanone A mixture of 24.2 mg (0.134 mmol) <strong>[15897-81-1]adamantane-2-carboxylic acid</strong>, 20 mg (0.168 mmol) indoline, 64.7 mg (0.2 mmol) TBTU and 43.4 mg (0.336 mmol) DIPEA in 1 mL DMF was stirred at room temperature overnight. Formic acid was added and the mixture was subjected to column chromatography on reversed phase eluting with a gradient formed from acetonitrile, water and NEt3 to yield after evaporation of the product containing fractions 14.1 mg (30%) of the title compound. MS(m/e): 282.4 (MH+).
  • 67
  • [ 496-15-1 ]
  • [ 631912-19-1 ]
  • 1-(3-bromo-4-(cyclopropylmethoxy)phenylsulfonyl)indoline [ No CAS ]
  • 68
  • [ 496-15-1 ]
  • [ 628-09-1 ]
  • C13H17NO2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; In isopropyl alcohol; for 12h;Reflux; Indoline (92.05g, 0.774mol), 3-chloropropanolacetate (122.0g, 0.893mol) and N,N-diisopropyl ethylamine(336.2mL, 1.935ml) were charged successively into 1000 ml tree-neck round-bottom flask, equipped with a mechanicalstirrer and reflux condenser. Isopropanol was added and then reacted at reflux for 12 hours. Most of the isopropanol inthe reaction liquid was removed by distillation under reduced pressure. The mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate. Removal of the solvent by distillation under reduced pressureafforded 189g the crude compound of formula 1 as a deep red solid, which was used directly in the next step withoutfurther purification. 1HNMR (400MHz, CDCl3): delta=1.953-1.987(m, 2H), delta=2.102(s, 3H), delta=2.971-3.012 (t, 2H, J=8.4Hz),delta=3.159-3.195 (t, 2H, J=7.2Hz), delta=3.346-3.388 (t, 2H, J=8.4Hz), delta=4.203-4.235 (t, 2H, J=6.4Hz), delta=6.484-6.504 (d, 1H,J=8Hz), delta=6.660-6.697 (t, 1H, J=7.2Hz), delta=7.072-7.110 (m, 2H)
With N-ethyl-N,N-diisopropylamine; In isopropyl alcohol; for 12h;Reflux; 10117] Indoline (92.05 g, 0.774 mol), 3-chloropropanolac- etate (122.0 g, 0.893 mol) and N,N-diisopropyl ethylamine (336.2 mE, 1.935 mol) were charged successively into 1000 ml tree-neck round-bottom flask, equipped with a mechanical stirrer and reflux condenset Isopropanol was added and then reacted at reflux for 12 hours. Most of the isopropanol in the reaction liquid was removed by distillation under reduced pressure. The mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate. Removal of the solvent by distillation under reduced pressure afforded 189 g the crude compound of formula 1 as a deep red solid, which was used directly in the next step without further purification.10118] ?HNMR (400 MHz, CDC13): oe=i.953-i.987 (m,2H), oe=2.102 (s, 3H), oe=2.971-3.012 (t, 2H, J=8.4 Hz), oe=3.159-3.195 (t, 2H, J=7.2 Hz), oe=3.346-3.388 (t, 2H, J=8.4 Hz),oe=4.203-4.235 (t, 2H, J=6.4 Hz), oe=6.484-6.504 (d, 1H, J=8Hz), oe=6.660-6.697 (t, 1H, J=7.2 Hz), oe=7.072-7.ii0 (m,2H).
  • 69
  • [ 496-15-1 ]
  • [ 22821-76-7 ]
  • 7-[4-(methylsulfonyl)benzoyl]-1H-indoline [ No CAS ]
  • 70
  • [ 496-15-1 ]
  • [ 16019-31-1 ]
  • 1-(5-allyl-6-chloropyrimidin-4-yl)indoline [ No CAS ]
  • 71
  • [ 496-15-1 ]
  • [ 16019-31-1 ]
  • 8-chloro-6-methyl-1,2,6,7-tetrahydropyrimido[5',4':6,7]azepino-[3,2,1-hi]indole [ No CAS ]
  • 72
  • [ 496-15-1 ]
  • [ 239463-85-5 ]
  • 73
  • [ 496-15-1 ]
  • [ 6914-71-2 ]
  • dimethyl 2,3-dihydro-1H-pyrrolo[1,2-a]indole-1,1-dicarboxylate [ No CAS ]
  • 74
  • [ 496-15-1 ]
  • [ 18648-66-3 ]
  • C28H23N [ No CAS ]
  • 75
  • [ 496-15-1 ]
  • [ 538-23-8 ]
  • 1-octylindoline [ No CAS ]
  • 76
  • [ 496-15-1 ]
  • [ 608-08-2 ]
  • 2,3-dihydro-1,3'-bi-1H-indole [ No CAS ]
YieldReaction ConditionsOperation in experiment
69% With indium(III) tris[bis(trifluoromethanesulfonyl)amide]; In chlorobenzene; at 100℃; for 4h;Inert atmosphere; In (NTf 2) 3 (25 mumol) was placed in a container under reduced pressure,After heat treatment at 150 C. for 2 hours,After cooling to room temperature,The atmosphere was replaced with argon.To this was added chlorobenzene (1 mL)The contents were stirred at room temperature for 10 min.Further, compound (1alpha) (0.625 mmol) represented by the following formula and compound (2) (0.25 mmol) were added thereto,The reaction was carried out at 110 C. for 24 hours.Tables 1 and 2 show the amount of each raw material compound used and the reaction conditions.In Table 1,The amount of Lewis acid used is,It is shown in "mol%" unit.After completion of the reaction,Saturated aqueous sodium hydrogen carbonate solution (0.5 mL) was added to the reaction solution,The aqueous layer was extracted three times with ethyl acetate (5 mL)The organic layer was washed with saturated brine (2 mL)After dehydration with anhydrous sodium sulfate and filtration,After concentration under reduced pressure,The obtained concentrate was purified by silica gel column chromatography (mobile phase: n-hexane / ethyl acetate (10/1, volume ratio)),The target compound (3101) was taken out as a yellow liquid.The isolation yield of the compound (3101) was 63%The NMR conversion yield was 66%The NMR conversion yield almost agreed with the isolated yield. subjected to reaction under conditions shown in Tables 3 and 4, the concentrate was purified by silica gel column chromatography (mobile phase: n-hexane / ethyl acetate (5/1, volume ratio)) except that purified by, in the same manner as in example 1 to give compound as a brown solid (the 3302) (69% isolated yield).
  • 77
  • [ 496-15-1 ]
  • [ 123-54-6 ]
  • [ 16078-30-1 ]
  • 78
  • [ 496-15-1 ]
  • [ 144034-80-0 ]
  • 79
  • [ 496-15-1 ]
  • [ 84223-13-2 ]
  • [ 16078-30-1 ]
  • 80
  • [ 496-15-1 ]
  • [ 107-21-1 ]
  • [ 90874-78-5 ]
  • [ 121459-15-2 ]
YieldReaction ConditionsOperation in experiment
With palladium on activated charcoal; zinc(II) oxide; In water; at 150℃; for 24h;Sealed tube; General procedure: 1 mmol of amine, 0.07 mmol of Pd/C, 3 mmol of ZnO, 6 mL of distilled water and 6 mL of ethylene glycol were mixed manually inside a 20 mL Teflon flask. Then it was sealed into a steel autoclave and introduced in a preheated oven at 150 C for 24 h. The reaction mixture was cooled to room temperature, 25 mL of distilled water were added and the crude was filtered through a 0.2 mm Teflon filter. The reaction mixture was extracted with ethyl acetate3 15 ml and organic layers were combined, dried with Na2SO4, filtered and concentrated affording the reaction crude that was cheeked by NMR. Crude reaction was purified by chromatotron (1 mm, silica, from hexane to hexane/AcOEt 1:3) affording pure beta-amino alcohols.
  • 81
  • [ 496-15-1 ]
  • [ 62595-74-8 ]
  • 3-(indolin-1-yl)piperidine-2,6-dione [ No CAS ]
YieldReaction ConditionsOperation in experiment
53% In tetrahydrofuran; at 70℃; for 16h; General procedure: This was obtained as a beige solid (62 mg, 53%) from MA6-019 (150 mg, 1 equiv.) and indoline (62.0 mg, 1 equiv.) using the general method 1 (Scheme 1) (reaction temperature 70 C, solvent THF, reaction time 16 h). Purification was carried out using SiO2 column chromatography (eluent: MeOH-DCM, up to 15% MeOH). HPLC: 99% [tR = 13.6 min, Gradient 5-95% MeOH-water (with 0.1% TFA), 20 min].1H NMR (400 MHz, DMSO-d6) delta 10.81 (s, 1H), 7.01 (J = 7.2, 0.8 Hz, 1H), 6.93 (td, J = 7.8, 0.8 Hz, 1H), 6.53 (td, J = 7.4, 0.9 Hz, 1H), 6.48 (d, J = 7.8 Hz, 1H), 4.63 (dd, J = 13.1, 4.9 Hz, 1H), 3.41 (ddd, J = 9.6, 8.4, 5.9 Hz, 1H), 3.27 (q, J = 9.3 Hz, 1H), 2.99- 2.87 (m, 2H), 2.79 (ddd, J = 17.4, 13.5, 5.4 Hz, 1H), 2.62-2.58 (m, 1H), 2.20 (qd, J = 13.1, 4.4 Hz, 1H), 2.01- 1.92 (m, 1H). HPLC-MS (ESI): ): m/z 231.2 [100%, (M+H)+]. LC-MS (ESI+): 231.1 [100%, (M+H]. HRMS (ESI+): m/z calcd for C13H14N2O2 (M)+ 230.1055, found 230.1056.
  • 82
  • [ 16078-30-1 ]
  • [ 496-15-1 ]
  • [ 5876-09-5 ]
YieldReaction ConditionsOperation in experiment
97%; 2% With triethyl borane; Triethoxysilane; sodium hydroxide; In hexane; at 80℃; for 6h;Inert atmosphere; Sealed tube; Under argon atmosphere, NaOH and triethyl boron were first stirred at room temperature to form a clear clear solution at a concentration of 1 M / L;Subsequently, 10 mol (2 mol%) of the above-mentioned triethylboron solution, 5 mmol of amide substrate, 15 mmol of silane, 2 mL of solventInto a 10 mL sealed tube and placed in an oil bath at 80 C for 6 hours with heating. The reaction was completed and the reaction was exposed to air quenching, followed byThe yield was determined by column chromatography and gas chromatography and a pure product was obtained. When using polymethylhydrogensiloxane (PMHS) andWhen the tetrahydrofuran was used as the silane and the solvent, the yields of the products A and B were 88% and 1%, respectively. When the triethoxysilaneAnd n-hexane were used as silane and solvent, the yields of products A and B were respectively 97%, 2%
  • 83
  • [ 496-15-1 ]
  • [ 107-21-1 ]
  • [ 121459-15-2 ]
  • 84
  • [ 496-15-1 ]
  • [ 160538-51-2 ]
  • 1-(3-fluoro-4-nitrobenzyl)indoline [ No CAS ]
YieldReaction ConditionsOperation in experiment
62% To a solution ofcompound68(5.40 g, 31.95 mmol) in ClCH2CH2Cl (20 mL) wasadded indoline (2.97 mL, 26.63 mmol) at 0 C. The reaction mixturewas stirred at 0 C for 30 min, then NaBH(OAc)3(6.77 g, 31.95 mmol)was added, and stirred at 0 C for another 5 h. The reaction wasmonitored by TLC. Upon completion, the reaction mixture wasdiluted with saturated NaHCO3, and extracted with EtOAc(3 40 mL). The combined organic extracts were washed withbrine, dried (Na2SO4), and concentrated under reduced pressure.The crude proudct was purified by flash column chromatography(gradient elution, gradient 0 to 10% EtOAc/60e90 C petroleumether) to give compound69(5.38 g, 19.76 mmol, 62% yield) as redliquid.1H NMR (400 MHz, CDCl3) d 8.06 (t, J 8.0 Hz, 1H), 7.36 (d,J 11.7 Hz, 1H), 7.34e7.30 (m, 1H), 7.16 (d, J 7.2 Hz, 1H), 7.07 (t,J 7.7 Hz, 1H), 6.75 (t, J 7.4 Hz, 1H), 6.40 (d, J 7.8 Hz, 1H), 4.32 (s,2H), 3.41 (t, J 8.2 Hz, 2H), 3.06 (t, J 8.3 Hz, 2H).
  • 85
  • [ 51792-34-8 ]
  • [ 496-15-1 ]
  • 2,3-dihydro-1-(4-methoxy-3-thienyl)-1H-indole [ No CAS ]
  • 86
  • [ 496-15-1 ]
  • [ 890315-72-7 ]
  • [ 910241-03-1 ]
  • 87
  • [ 67-56-1 ]
  • [ 496-15-1 ]
  • [ 27465-51-6 ]
  • 1-(4-ethylphenyl)-3-(indolin-1-yl)-2-methylpropan-1-one [ No CAS ]
  • 88
  • [ 67-56-1 ]
  • [ 496-15-1 ]
  • [ 63740-97-6 ]
  • 1-(benzo[d][1,3]dioxol-5-yl)-2-(indolin-1-ylmethyl)butan-1-one [ No CAS ]
  • 89
  • [ 496-15-1 ]
  • [ 70639-77-9 ]
  • 6-(indoline-1-carbonyl)-3,4-dihydro-1H-quinolin-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
3% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 25℃; for 16.0h; To a stirred solution of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (902 mg)and 1-hydroxybenzotriazole (636 mg) in N,N-dimethylformamide (3 ml) were added <strong>[70639-77-9]2-oxo-3,4-dihydro-1H-quinoline-6-carboxylic acid</strong>88 (300 mg) and indoline33 (0.23 ml) and then the reaction mixture was stirred at 25 C for 16 hours. The reaction was diluted into water (10 ml) and extracted with ethyl acetate (2 x 5 ml).The combined organic phases were concentrated in vacuo and the residue was purified by preparative HPLC to give 6-(indoline-1-carbonyl)-3,4-dihydro-1H-quinolin-2-one (14.4 mg, 3 %) as a yellow solid. MS (ISP): 307.2 ([M+H]j.
  • 90
  • [ 496-15-1 ]
  • [ 52914-23-5 ]
  • [ 1745-81-9 ]
  • C25H27NO2 [ No CAS ]
  • 91
  • [ 496-15-1 ]
  • [ 1745-81-9 ]
  • [ 175278-00-9 ]
  • C24H22F3NO2 [ No CAS ]
  • 92
  • [ 496-15-1 ]
  • [ 608-28-6 ]
  • [ 1745-81-9 ]
  • C25H27NO [ No CAS ]
  • 93
  • [ 496-15-1 ]
  • [ 19230-28-5 ]
  • [ 1745-81-9 ]
  • C23H21Cl2NO [ No CAS ]
  • 94
  • [ 496-15-1 ]
  • [ 101335-11-9 ]
  • [ 1745-81-9 ]
  • C23H21ClFNO [ No CAS ]
  • 95
  • [ 496-15-1 ]
  • acetyl derivative [ No CAS ]
  • [ 16078-30-1 ]
  • 96
  • [ 496-15-1 ]
  • [ 6292-59-7 ]
  • [ 563-63-3 ]
  • [ 64-19-7 ]
  • [ 1612872-85-1 ]
YieldReaction ConditionsOperation in experiment
72% With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; [bis(acetoxy)iodo]benzene; silver trifluoromethanesulfonate; In 1,2-dichloro-ethane; at 100℃; for 16h;Schlenk technique; In the dried Schrank tube, raw porphyrin (0.15 mmol, 24.2 mg), p-tert-butylbenzenesulfonamide (0.3 mmol, 63.9 mg),Iodobenzene acetate (0.15 mmol, 48.3 mg), pentamethylcyclopentadienylphosphonium dichloride (5 mmolpercent, 4.6 mg), silver triflate (20 mmolpercent, 7.7 mg),Silver acetate (20 mmolpercent, 5.1 mg), acetic acid (0.45 mmol, 27 mg) 1,2-dichloroethane 1.5 mL, and the above-mentioned Schlank tube was placed in a 100 o C oil bath.Stir for about 16 h. The reaction was terminated, and the reaction liquid was easily quenched with 2 mL of saturated ammonium chloride, and then extracted with ethyl acetate (4 mL × 5), and then the organic phase was combined.The solvent was removed on a rotary evaporator. Finally, it was separated by silica gel column chromatography (eluent: ethyl acetate: petroleum ether = 1: 5).Obtaining N-(1-acetylporphyrin-7-yl)-<strong>[6292-59-7]4-(tert-butyl)benzenesulfonamide</strong> 3l(40.1 mg, isolated yield: 72percent).This compound was a pale yellow solid.
  • 97
  • [ 496-15-1 ]
  • [ 3119-02-6 ]
  • [ 563-63-3 ]
  • [ 64-19-7 ]
  • N-(1-acetylindolin-7-yl)-4-cyanobenzenesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
35% With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; [bis(acetoxy)iodo]benzene; silver trifluoromethanesulfonate; In 1,2-dichloro-ethane; at 100℃; for 16h;Schlenk technique; In the dried Schrank tube, raw porphyrin (0.15 mmol, 24.2 mg), <strong>[3119-02-6]p-cyanobenzenesulfonamide</strong> (0.3 mmol, 54.6 mg),Iodobenzene acetate (0.15 mmol, 48.3 mg), pentamethylcyclopentadienylphosphonium dichloride (5 mmol%, 4.6 mg), silver triflate (20 mmol%, 7.7 mg),Silver acetate (20 mmol%, 5.1 mg), acetic acid (0.45 mmol, 27 mg) 1,2-dichloroethane 1.5 mL, and the above-mentioned Schlank tube was placed in a 100 o C oil bath.Stir for about 16 h. The reaction was terminated, and the reaction solution was easily quenched with 2 mL of saturated ammonium chloride, and then extracted with ethyl acetate (4 mL×5).The solvent was removed on a rotary evaporator. Finally, it was separated by silica gel column chromatography (eluent: ethyl acetate: petroleum ether = 1: 5) to give N-(1- acetyl porphyrin-7-yl)-4-methoxybenzenesulfonamide 3p (17.9 mg, isolated yield: 35%),This compound was a pale yellow solid.
  • 99
  • [ 496-15-1 ]
  • [ 13101-83-2 ]
  • 1-(6-fluoronaphthalen-2-yl)-1H-indole [ No CAS ]
  • 100
  • [ 141519-77-9 ]
  • [ 496-15-1 ]
  • 1-chloro-5-indolin-1-ylsulfonylisoquinoline [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In dichloromethane; at 15℃; for 2.0h;Inert atmosphere; Example 3 5-(indolin-1-ylsulfonyl)isoquinolin-1(2H)-one Compound 3-1: To a solution of <strong>[141519-77-9]1-chloroisoquinoline-5-sulfonylchloride</strong> (0.3 g, 1.14 mmol) in DCM (8 mL) was added TEA (238.9 muL, 1.72 mmol) and indoline (109.1 mg, 915.6 mumol). The mixture was stirred at 15 C. for 12 h under an N2 atmosphere. The reaction mixture was diluted with H2O (60 mL) and extracted with EtOAc (100 mL*3). The combined organic layers were washed with saturated brine (50 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give a residue. The crude product, Compound 3-1, 1-chloro-5-indolin-1-ylsulfonyl-isoquinoline (0.2 g, crude) was obtained as a yellow solid. Compound 3-1 was used in the next step without further purification.
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