Dimethylacetamide → HCID 178461235, Verbindung

HRID 1852881Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1852881
[CH2:1]([O:8][C:9]1[C:14]([C:15]2[C:20]3[N:21]([CH2:33][C@H:34]4[CH2:39][CH2:38][C@H:37]([CH3:40])[CH2:36][CH2:35]4)[C:22]([N:24]4[CH2:29][CH2:28][O:27][C@@H:26]5[CH2:30][CH2:31][CH2:32][C@@H:25]45)=[N:23][C:19]=3[CH:18]=[C:17](Cl)[N:16]=2)=[CH:13][C:12]([Cl:42])=[CH:11][N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[C:44]([N:46](C)C)=O>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[CH2:1]([O:8][C:9]1[C:14]([C:15]2[C:20]3[N:21]([CH2:33][C@H:34]4[CH2:39][CH2:38][C@H:37]([CH3:40])[CH2:36][CH2:35]4)[C:22]([N:24]4[CH2:29][CH2:28][O:27][C@@H:26]5[CH2:30][CH2:31][CH2:32][C@@H:25]45)=[N:23][C:19]=3[CH:18]=[C:17]([C:44]#[N:46])[N:16]=2)=[CH:13][C:12]([Cl:42])=[CH:11][N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Komponenten

6

Edukt 2

HCID 31374DimethylacetamideHCID 178461233HCID 178461233, Verbindung

Produkt 1

HCID 178461235HCID 178461235, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 11186Zinc cyanide (Zn(CN)2)KatalysatorHCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

4-[2-(benzyloxy)-5-chloropyridin-3-yl]-6-chloro-2-[(trans)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine (racemic, 450 mg, 0.74 mmol), zinc cyanide (43 mg, 0.37 mmol) and Pd(PPh3)4 (128 mg, 0.11 mmol) were placed in a dry vial. Degassed DMA (4 mL) was added to the reaction, and the reaction was placed under an atmosphere of Ar, sealed, and heated at 90° C. for 12 hours. The reaction was then cooled to room temperature, and cold water was added slowly. The aqueous layer was extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. Purification of the residue on a silica gel column (0 to 50% EtOAc/hexanes) afforded 4-[2-(benzyloxy)-5-chloropyridin-3-yl]-2-[(trans)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile as a racemic mixture. The enantiomers were separated on a chiral OD column using 2% IPA/98% heptanes. MS ES calc'd. for C34H37ClN6O2 [M+H]+ 597. found 597.

Aufarbeitung

  1. customsealed
  2. temperatureThe reaction was then cooled to room temperature
  3. extractionThe aqueous layer was extracted with EtOAc
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customPurification of the residue on a silica gel column (0 to 50% EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-62928b8339624dcb8a7253ece0aced3f
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08962611B2

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