Cesium fluoride → 7-(2-Chlorophenyl)-3-(3-(ethyl(1-naphthyl)amino)propyl)-1h-indole-2-carboxylic acid

HRID 2095279Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2095279
Br[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][C:8]([C:11]([O:13]CC)=[O:12])=[C:7]2[CH2:16][CH2:17][CH2:18][N:19]([CH2:30][CH3:31])[C:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:23]=[CH:22][CH:21]=1.[Cl:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1B(O)O.F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.[F-].[Cs+]>O1CCCC1.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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][C:8]([C:11]([OH:13])=[O:12])=[C:7]2[CH2:16][CH2:17][CH2:18][N:19]([CH2:30][CH3:31])[C:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:23]=[CH:22][CH:21]=1

Komponenten

7

Edukt 4

HCID 25953Cesium fluorideHCID 27343222-Chlorophenylboronic acidHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 68938635Ethyl 7-bromo-3-(3-(ethyl(naphthalen-1-yl)amino)propyl)-1h-indole-2-carboxylate

Produkt 1

HCID 689371517-(2-Chlorophenyl)-3-(3-(ethyl(1-naphthyl)amino)propyl)-1h-indole-2-carboxylic acid

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a mixture of EXAMPLE 531B (192 mg) and 2-chlorophenylboronic acid (76 mg) in tetrahydrofuran (6 ml) was added tris(dibenzylideneacetone)dipalladium(0) (19 mg), tri-t-butyl-phosphonium tetrafluoroborate (12 mg) and cesium fluoride (200 mg). The mixture was purged with argon and stirred at room temperature for 24 hours. The mixture was diluted with ethyl acetate (200 mL) and washed with water, and brine and dried over Na2SO4. Concentration of the mixture and column purification of the crude material (5% ethyl acetate in hexane) provided the title compound. A portion of this material (50 mg) was dissolved in 1:1 tetrahydrofuran/methanol with a few drops of water and hydrolyzed with LiOH. Subsequent purification via RP HPLC afforded the title compound. 1H NMR (300 MHz, DMSO-d6) 10.80 (m, 1H), 8.27 (m, 1H), 7.90 (m, 1H), 7.55 (m, 1H), 7.53 (m, 1H), 7.42 (m, 3H), 7.34 (m, 3H), 7.21 (m, 2H), 7.03 (m, 1H), 6.98 (m, 2H), 3.21 (m, 4H), 3.08 (t, 2H), 1.79 (m, 2H), 0.96 (t, 3H).

Aufarbeitung

  1. customThe mixture was purged with argon
  2. additionThe mixture was diluted with ethyl acetate (200 mL)
  3. washwashed with water, and brine
  4. dry with materialdried over Na2SO4
  5. customConcentration of the mixture and column purification of the crude material (5% ethyl acetate in hexane)

Quellen und Nachweise

ORD-Eintrag
ord-b57b79a09eb24556905acf1e5a076b2d
Quelldatensatz
uspto-grants-2013_05
Patentnummer
US08445679B2

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