Tributylphosphine → 4-((5-Chloro-2-thienyl)methoxy)-1-(2-((1RS,2SR)-2-(2-hydroxypropan-2-yl)cyclopropyl)-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-one

HRID 2203031Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2203031
[OH:1][C:2]1[CH:7]=[CH:6][N:5]([C:8]2[CH:9]=[CH:10][C:11]3[N:15]=[C:14]([CH:16]4[CH2:18][CH:17]4[C:19]([OH:22])([CH3:21])[CH3:20])[N:13]([CH3:23])[C:12]=3[CH:24]=2)[C:4](=[O:25])[CH:3]=1.[Cl:26][C:27]1[S:31][C:30]([CH2:32]O)=[CH:29][CH:28]=1.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>C1COCC1>[Cl:26][C:27]1[S:31][C:30]([CH2:32][O:1][C:2]2[CH:7]=[CH:6][N:5]([C:8]3[CH:9]=[CH:10][C:11]4[N:15]=[C:14]([CH:16]5[CH2:18][CH:17]5[C:19]([OH:22])([CH3:20])[CH3:21])[N:13]([CH3:23])[C:12]=4[CH:24]=3)[C:4](=[O:25])[CH:3]=2)=[CH:29][CH:28]=1

Komponenten

6

Edukt 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 12554178(5-Chlorothiophen-2-yl)methanolHCID 1213862594-Hydroxy-1-(2-((1RS,2SR)-2-(2-hydroxypropan-2-yl)cyclopropyl)-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-one

Produkt 1

HCID 897025734-((5-Chloro-2-thienyl)methoxy)-1-(2-((1RS,2SR)-2-(2-hydroxypropan-2-yl)cyclopropyl)-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-oneAusbeute 21 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

To a mixture of 4-hydroxy-1-(2-((1RS,2SR)-2-(2-hydroxypropan-2-yl)cyclopropyl)-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-one (100 mg), (5-chloro-2-thienyl)methanol (88 mg), tributylphosphine (0.219 ml) and THF (10 ml) was added 1,1′-(azodicarbonyl)dipiperidine (223 mg), and the mixture was stirred at 60° C. for 2 h. The reaction mixture was partitioned between EtOAc and water, and the organic layer was washed with brine, dried over MgSO4, and concentrated in vacuo. The residue was purified by NH silica gel column chromatography (EtOAc/MeOH), followed by silica gel column chromatography (hexane/EtOAc then EtOAc/MeOH). The resulting solid was recrystallized from IPE-IPA to give the title compound (29.1 mg) as an off-white solid.

Aufarbeitung

  1. customThe reaction mixture was partitioned between EtOAc and water
  2. washthe organic layer was washed with brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by NH silica gel column chromatography (EtOAc/MeOH)
  6. customThe resulting solid was recrystallized from IPE-IPA

Quellen und Nachweise

ORD-Eintrag
ord-95333d0b1ba3423d8d880c5d325886ec
Quelldatensatz
uspto-grants-2016_06
Patentnummer
US09365540B2

Notizen zur Reaktion

Wird geladen…