1,2-Dichloroethane → 2-[(4S,6S)-6-(3,5-Difluorophenyl)-4-hydroxy-3,3-dimethyl-2-oxopiperidin-1-yl]-N-[(2R)-2'-oxo-1,1',2',3-tetrahydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-5-yl]acetamide

HRID 1367247Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1367247
[F:1][C:2]1[CH:3]=[C:4]([C@H:9]2[N:14]([CH2:15][C:16]([OH:18])=O)[C:13](=[O:19])[C:12]([CH3:21])([CH3:20])[C@@H:11]([OH:22])[CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1.[NH2:23][C:24]1[CH:25]=[C:26]2[C:39](=[CH:40][CH:41]=1)[CH2:38][C@:28]1([C:36]3[C:31](=[N:32][CH:33]=[CH:34][CH:35]=3)[NH:30][C:29]1=[O:37])[CH2:27]2.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([C@H:9]2[N:14]([CH2:15][C:16]([NH:23][C:24]3[CH:25]=[C:26]4[C:39](=[CH:40][CH:41]=3)[CH2:38][C@:28]3([C:36]5[C:31](=[N:32][CH:33]=[CH:34][CH:35]=5)[NH:30][C:29]3=[O:37])[CH2:27]4)=[O:18])[C:13](=[O:19])[C:12]([CH3:20])([CH3:21])[C@@H:11]([OH:22])[CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1

Komponenten

6

Edukt 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 53260812(R)-5-Amino-1,3-dihydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one2×HCID 57974108[(4S,6S)-6-(3,5-Difluorophenyl)-4-hydroxy-3,3-dimethyl-2-oxopiperidin-1-yl]acetic acid2×

Produkt 1

HCID 250207582-[(4S,6S)-6-(3,5-Difluorophenyl)-4-hydroxy-3,3-dimethyl-2-oxopiperidin-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 [(4S,6S)-6-(3,5-difluorophenyl)-4-hydroxy-3,3-dimethyl-2-oxopiperidin-1-yl]acetic acid (130 mg, 0.415 mmol, described in Intermediate 21), (R)-5-amino-1,3-dihydro spiro[indene-2,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (140 mg, 0.557 mmol, described in Intermediate 9), HOBT (82 mg, 0.535 mmol), and EDC (95 mg, 0.498 mmol) in DMF (2 mL) was stirred at ambient temperature for 6 h. The reaction mixture was partitioned between H2O (50 mL), saturated aqueous NaHCO3 (30 mL) and EtOAc (100 mL). The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of CH2Cl2:CH3OH—100:0 to 90:10, to give the title compound. MS: m/z=547 (M+1). HRMS: m/z=547.2169; calculated m/z=547.2151 for C30H29F2N4O4.

Aufarbeitung

  1. customThe reaction mixture was partitioned between H2O (50 mL), saturated aqueous NaHCO3 (30 mL) and EtOAc (100 mL)
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by silica gel chromatography
  6. washeluting with a gradient of CH2Cl2

Quellen und Nachweise

ORD-Eintrag
ord-077fac7e7edf48df9afa3e96f457bbf1
Quelldatensatz
uspto-grants-2011_02
Patentnummer
US07893079B2

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