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Cesium carbonate → 5-(3-(ethylsulfonyl)phenyl)-3-methyl-8-((1-methylpiperidin-4-yl)methoxy)-9H-pyrido[2,3-b]indole

HRID 1642561
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1642561
Cl[C:2]1[CH:10]=[CH:9][C:8]([O:11][CH2:12][CH:13]2[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]2)=[C:7]2[C:3]=1[C:4]1[CH:23]=[C:22]([CH3:24])[CH:21]=[N:20][C:5]=1[NH:6]2.[CH2:25]([S:27]([C:30]1[CH:31]=[C:32](B(O)O)[CH:33]=[CH:34][CH:35]=1)(=[O:29])=[O:28])[CH3:26].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.C([O-])([O-])=O.[Cs+].[Cs+]>CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].O1CCOCC1>[CH2:25]([S:27]([C:30]1[CH:35]=[C:34]([C:2]2[CH:10]=[CH:9][C:8]([O:11][CH2:12][CH:13]3[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]3)=[C:7]3[C:3]=2[C:4]2[CH:23]=[C:22]([CH3:24])[CH:21]=[N:20][C:5]=2[NH:6]3)[CH:33]=[CH:32][CH:31]=1)(=[O:28])=[O:29])[CH3:26]
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

8

Edukt 4

HCID 10796Cesium carbonateHCID 75806TricyclohexylphosphineHCID 164271023-Ethylsulfonylphenylboronic acidHCID 588801545-chloro-3-methyl-8-((1-methylpiperidin-4-yl)methoxy)-9H-pyrido[2,3-b]indole

Produkt 1

HCID 588800825-(3-(ethylsulfonyl)phenyl)-3-methyl-8-((1-methylpiperidin-4-yl)methoxy)-9H-pyrido[2,3-b]indole
Ausbeute 75,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumKatalysatorHCID 8857Ethyl AcetateLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
125 °C

Versuchsvorschrift

To a stirred solution of Compound 175 (170 mg, 0.49 mmol) and 3-(ethylsulfonyl)phenylboronic acid (265 mg, 1.24 mmol) in anhydrous and degassed dioxane (5 mL), were added Pd(dba)2 (70 mg, 0.12 mmol), PCy3 (0.34 mL, 20% wt solution in toluene, 0.24 mmol) and Cs2CO3 (479 mg, 1.47 mmol), under nitrogen. After being stirred for 6 h. under reflux (oil bath temperature 125° C.) the reaction was diluted with EtOAc and filtered through a small pad of celite. The residue was washed thoroughly with EtOAc and 10% MeOH in CH2Cl2. All the washings and filtrate were concentrated in vacuum and the crude residue was triturated with ether and then with MeOH and then purified through preparative HPLC to give Compound 176 (176 mg, 75%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.20 (t, J=7.34 Hz, 3 H) 1.50-1.61 (m, 2 H) 2.18 (br. s., 1 H) 2.13-2.20 (m, 1 H) 2.23-2.31 (m, 5 H) 2.82 (s, 3 H) 2.98-3.09 (m, 2 H) 3.39 (q, J=7.34 Hz, 2 H) 3.54 (d, J=10.60 Hz, 2 H) 4.12 (d, J=6.52 Hz, 2 H) 7.06-7.17 (m, 2 H) 7.53 (s, 1 H) 7.85 (t, J=7.74 Hz, 1 H) 7.96 (d, J=7.66 Hz, 1 H) 8.00 (d, J=7.66 Hz, 1 H) 8.06 (s, 1 H) 8.28 (d, J=1.47 Hz, 1 H) 11.83 (br. s., 1 H), [M+H] calc'd for C27H32N3O3S, 478.2; found, 478.4; [M+H+TFA] calc'd for C29H33N3O5F3S, 592.2; found, 592.4.

Aufarbeitung

  1. filtrationfiltered through a small pad of celite
  2. washThe residue was washed thoroughly with EtOAc and 10% MeOH in CH2Cl2
  3. concentrationAll the washings and filtrate were concentrated in vacuum
  4. customthe crude residue was triturated with ether
  5. customwith MeOH and then purified through preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-51d0047f21e84cad86114faa5a24de12
Quelldatensatz
uspto-grants-2012_02
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08119655B2

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