Morpholine → N-(3,4-Difluorobenzyl)-2-isopropyl-6-morpholino-1-(pyridin-2-ylmethyl)-1H-indole-3-carboxamide

HRID 40160

Reaktionsgleichung

Reaktionsgleichung von HRID 40160
FC(F)(F)S(O[C:7]1[CH:15]=[C:14]2[C:10]([C:11]([C:26](=[O:37])[NH:27][CH2:28][C:29]3[CH:34]=[CH:33][C:32]([F:35])=[C:31]([F:36])[CH:30]=3)=[C:12]([CH:23]([CH3:25])[CH3:24])[N:13]2[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=2)=[CH:9][CH:8]=1)(=O)=O.[NH:40]1[CH2:45][CH2:44][O:43][CH2:42][CH2:41]1.[Li]N([Si](C)(C)C)[Si](C)(C)C.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>C1(C)C=CC=CC=1.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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:36][C:31]1[CH:30]=[C:29]([CH:34]=[CH:33][C:32]=1[F:35])[CH2:28][NH:27][C:26]([C:11]1[C:10]2[C:14](=[CH:15][C:7]([N:40]3[CH2:45][CH2:44][O:43][CH2:42][CH2:41]3)=[CH:8][CH:9]=2)[N:13]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=2)[C:12]=1[CH:23]([CH3:24])[CH3:25])=[O:37]

Komponenten

8

Edukt 4

HCID 8083MorpholineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 866216073-(3,4-Difluorobenzylcarbamoyl)-2-isopropyl-1-(pyridin-2-ylmethyl)-1H-indol-6-yl trifluoromethanesulfonate2×HCID 178418261HCID 178418261, Verbindung

Produkt 1

HCID 59762287N-(3,4-Difluorobenzyl)-2-isopropyl-6-morpholino-1-(pyridin-2-ylmethyl)-1H-indole-3-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 1140TolueneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

To a solution of 3-(3,4-difluorobenzylcarbamoyl)-2-isopropyl-1-(pyridin-2-ylmethyl)-1H-indol-6-yl trifluoromethanesulfonate (Compound 202, 100 mg, 0.18 mmol) in toluene (10 ml) at 25° C., bubbled with argon then added morpholine (22 mg, 0.25 mmol), LiN(TMS)2 (1M in THF, 0.37 ml, 0.40 mmol), Pd2 (dba)3 (3.2 mg, 0.0035 mmol), and X-Phos (4 mg, 0.011 mmol). The reaction was stirred for 12 h at 110° C., diluted with EtOAc, the organic layer was washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by chromatography on silica gel (0→100% EtOAc-hexanes) to yield the title compound as a light brown solid.

Aufarbeitung

  1. washthe organic layer was washed with brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by chromatography on silica gel (0→100% EtOAc-hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-d6d15a728d194b5185c373c04264493d
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08524917B2

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