Triphenylphosphine → (R)-4-((R)-1-(3-(difluoromethyl)-6-(3,4-dimethoxyphenyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one

HRID 2209003Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2209003
[F:1][CH:2]([F:23])[N:3]1[C:7]2[C:8](=[O:22])[NH:9][C:10]([C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([O:20][CH3:21])[CH:13]=3)=[CH:11][C:6]=2[N:5]=[CH:4]1.O[C@H:25]([C@H:27]1[CH2:31][N:30]([C@@H:32]([C:34]2[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=2)[CH3:33])[C:29](=[O:42])[CH2:28]1)[CH3:26].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1.C(Cl)Cl>[F:23][CH:2]([F:1])[N:3]1[C:7]2[C:8]([O:22][C@@H:25]([C@H:27]3[CH2:31][N:30]([C@@H:32]([C:34]4[CH:35]=[CH:36][C:37]([O:40][CH3:41])=[CH:38][CH:39]=4)[CH3:33])[C:29](=[O:42])[CH2:28]3)[CH3:26])=[N:9][C:10]([C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([O:20][CH3:21])[CH:13]=3)=[CH:11][C:6]=2[N:5]=[CH:4]1

Komponenten

7

Edukt 4

HCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 71238294(4R)-4-[(1S)-1-hydroxyethyl]-1-[(1R)-1-(4-methoxyphenyl)ethyl]pyrrolidin-2-oneHCID 1178438163-(difluoromethyl)-6-(3,4-dimethoxyphenyl)-3H-imidazo[4,5-c]pyridin-4(5H)-one

Produkt 1

HCID 117843944(R)-4-((R)-1-(3-(difluoromethyl)-6-(3,4-dimethoxyphenyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

3-(difluoromethyl)-6-(3,4-dimethoxyphenyl)-3H-imidazo[4,5-c]pyridin-4(5H)-one 2.29 (49 mg, 0.153 mmol), lactam alcohol 1.05 (60 mg, 0.23 mmol), and PPh3 (60 mg, 0.23 mmol) were taken up in THF (2 mL). To the resulting suspension was added DEAD (38 μL, 0.24 mmol) dropwise. The resulting clear colorless solution was heated to 40° C. and stirred 15 h. The solution was then diluted with DCM and concentrated directly onto silica gel. Purification by silica gel chromatography gave (R)-4-((R)-1-(3-(difluoromethyl)-6-(3,4-dimethoxyphenyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)-1-((R)-1-(4-methoxyphenyl)ethyl)pyrrolidin-2-one 2.30 that was used without further purification. LCMS-ESI+ (m/z): [M+H]+ calcd for C30H33F2N4O5: 567.2; found 567.4.

Aufarbeitung

  1. concentrationconcentrated directly onto silica gel
  2. customPurification by silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-43558ccb0d2b46f2a8d4e38e5ff5fadd
Quelldatensatz
uspto-grants-2016_06
Patentnummer
US09376441B2

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