Toluene → 4-(5-Cyano-2-pyridin-3-yl-indole-1-carbonyl)-benzoic acid methyl ester

HRID 593523

Reaktionsgleichung

Reaktionsgleichung von HRID 593523
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[NH:8][C:9]3[C:14]([CH:15]=2)=[CH:13][C:12]([C:16]#[N:17])=[CH:11][CH:10]=3)[CH:2]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].C1(C)C=CC=CC=1.[CH3:35][O:36][C:37](=[O:47])[C:38]1[CH:43]=[CH:42][C:41]([C:44](Cl)=[O:45])=[CH:40][CH:39]=1>C1COCC1>[CH3:35][O:36][C:37](=[O:47])[C:38]1[CH:43]=[CH:42][C:41]([C:44]([N:8]2[C:9]3[C:14](=[CH:13][C:12]([C:16]#[N:17])=[CH:11][CH:10]=3)[CH:15]=[C:7]2[C:3]2[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=2)=[O:45])=[CH:40][CH:39]=1

Komponenten

6

Edukt 4

HCID 1140TolueneHCID 81850Methyl 4-(chlorocarbonyl)benzoateHCID 3251421Potassium bis(trimethylsilyl)amideHCID 445541352-pyridin-3-yl-1H-indole-5-carbonitrile

Produkt 1

HCID 582155474-(5-Cyano-2-pyridin-3-yl-indole-1-carbonyl)-benzoic acid methyl ester

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of 2-pyridin-3-yl-1H-indole-5-carbonitrile (Example 8, 240 mg, 1.09 mmol) in THF (10 mL) at room temperature is added 0.5 M KHMDS in toluene (4.0 mL, 2.0 mmol). After 30 min, 4-chlorocarbonyl-benzoic acid methyl ester (400 mg, 2.0 mmol) is added. The mixture is stirred under N2 for 1 h. The reaction is quenched with aqueous sodium bicarbonate and the volatiles are removed in vacuo. Purification by silica gel flash chromatography using a heptane-ethyl acetate gradient affords 4-(5-cyano-2-pyridin-3-yl-indole-1-carbonyl)-benzoic acid methyl ester. 1H NMR (400 MHz, MeOD) δ ppm 3.90 (s, 3H), 7.12 (s, 1H), 7.26 (dd, J=8.0, 4.9 Hz, 1H), 7.63-7.72 (m, 3H), 7.77-7.81 (m, 1H), 7.91-7.96 (m, 3H), 8.17 (d, J=1.5 Hz, 1H), 8.32 (dd, J=4.8, 1.5 Hz, 1H), 8.56 (d, J=2.3 Hz, 1H). HRMS (ESI) m/z 382.1186 [(M+H)+ Calcd for C23H16N3O3: 382.1192].

Aufarbeitung

  1. customThe reaction is quenched with aqueous sodium bicarbonate
  2. customthe volatiles are removed in vacuo
  3. customPurification by silica gel flash chromatography

Quellen und Nachweise

ORD-Eintrag
ord-e58a1b088f1e4327af4b65e806b7e317
Quelldatensatz
uspto-grants-2016_01
Patentnummer
US09242963B2

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