1,2-Dichloroethane → 2-[(6R)-6-(3,5-Difluorophenyl)-3,3-diethyl-2-oxopiperazin-1-yl]-N-[(2R)-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-5-yl]acetamide

HRID 1866732Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1866732
Cl.[F:2][C:3]1[CH:4]=[C:5]([C@H:10]2[N:15]([CH2:16][C:17]([OH:19])=O)[C:14](=[O:20])[C:13]([CH2:23][CH3:24])([CH2:21][CH3:22])[NH:12][CH2:11]2)[CH:6]=[C:7]([F:9])[CH:8]=1.[NH2:25][C:26]1[CH:27]=[C:28]2[C:49](=[CH:50][CH:51]=1)[CH2:48][C@:30]1([C:38]3[C:33](=[N:34][CH:35]=[CH:36][CH:37]=3)[N:32](COCC[Si](C)(C)C)[C:31]1=[O:47])[CH2:29]2.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C=O)C>[F:2][C:3]1[CH:4]=[C:5]([C@H:10]2[N:15]([CH2:16][C:17]([NH:25][C:26]3[CH:27]=[C:28]4[C:49](=[CH:50][CH:51]=3)[CH2:48][C@:30]3([C:38]5[C:33](=[N:34][CH:35]=[CH:36][CH:37]=5)[NH:32][C:31]3=[O:47])[CH2:29]4)=[O:19])[C:14](=[O:20])[C:13]([CH2:21][CH3:22])([CH2:23][CH3:24])[NH:12][CH2:11]2)[CH:6]=[C:7]([F:9])[CH:8]=1

Komponenten

6

Edukt 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 66973301[(6R)-6-(3,5-Difluorophenyl)-3,3-diethyl-2-oxopiperazin-1-yl]acetic acid hydrochloride2×HCID 66973634(R)-5-amino-1'-{[2-(trimethylsilyl)ethoxy]methyl}-1,3-dihydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one2×

Produkt 1

HCID 250199382-[(6R)-6-(3,5-Difluorophenyl)-3,3-diethyl-2-oxopiperazin-1-yl]-N-[(2R)-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-5-yl]acetamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A mixture of [(6R)-6-(3,5-difluorophenyl)-3,3-diethyl-2-oxopiperazin-1-yl]acetic acid hydrochloride (43 mg, 0.119 mmol, described in Intermediate 29), (R)-5-amino-1,3-dihydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (30 mg, 0.119 mmol, described in Intermediate 9), HOBT (27 mg, 0.179 mmol), and EDC (34 mg, 0.179 mmol) in DMF (0.5 mL) was stirred at ambient temperature for 18 h. The reaction mixture was purified directly by HPLC using a reversed phase C18 column and eluting with a gradient of H2O:CH3CN:CF3CO2H—90:10:0.1 to 5:95:0.1. The pure, product-containing fractions were combined, basified with saturated aqueous NaHCO3, and extracted with EtOAc. The organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo to give the title compound. MS: m/z=560 (M+1). HRMS: m/z=560.2469; calculated m/z=560.2468 for C31H32F2N5O3.

Aufarbeitung

  1. customThe reaction mixture was purified directly by HPLC
  2. washeluting with a gradient of H2O
  3. additionThe pure, product-containing fractions
  4. extractionextracted with EtOAc
  5. dry with materialThe organic extracts were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-e3decf82225b4c47b0dae06fcd5d98af
Quelldatensatz
uspto-grants-2009_12
Patentnummer
US07629338B2

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