(5-Methyl-2-oxo-1,3-dioxol-4-yl)methyl 4-nitrophenyl carbonate → (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl ((S)-1-((R)-2,2,2-trifluoro-1-(3-(6-fluoro-7-(2-hydroxyethoxy)quinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)ethyl)pyrrolidin-3-yl)carbamate

HRID 339084Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 339084
[NH2:1][C@H:2]1[CH2:6][CH2:5][N:4]([C@H:7]([C:12]2[CH:13]=[CH:14][C:15]3[N:16]([C:18]([C:21]4[CH:30]=[CH:29][C:28]5[C:23](=[CH:24][C:25]([O:32][CH2:33][CH2:34][OH:35])=[C:26]([F:31])[CH:27]=5)[N:22]=4)=[N:19][N:20]=3)[CH:17]=2)[C:8]([F:11])([F:10])[F:9])[CH2:3]1.[C:36](=O)([O:46]C1C=CC([N+]([O-])=O)=CC=1)[O:37][CH2:38][C:39]1[O:40][C:41](=[O:45])[O:42][C:43]=1[CH3:44]>CN(C=O)C>[F:10][C:8]([F:9])([F:11])[C@H:7]([N:4]1[CH2:5][CH2:6][C@H:2]([NH:1][C:36](=[O:46])[O:37][CH2:38][C:39]2[O:40][C:41](=[O:45])[O:42][C:43]=2[CH3:44])[CH2:3]1)[C:12]1[CH:13]=[CH:14][C:15]2[N:16]([C:18]([C:21]3[CH:30]=[CH:29][C:28]4[C:23](=[CH:24][C:25]([O:32][CH2:33][CH2:34][OH:35])=[C:26]([F:31])[CH:27]=4)[N:22]=3)=[N:19][N:20]=2)[CH:17]=1

Komponenten

4

Edukt 2

HCID 10756264(5-Methyl-2-oxo-1,3-dioxol-4-yl)methyl 4-nitrophenyl carbonateHCID 709845612-(2-(6-((R)-1-((S)-3-aminopyrrolidin-1-yl)-2,2,2-trifluoroethyl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-6-fluoro quinolin-7-yloxy)ethanol

Produkt 1

HCID 70984291(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl ((S)-1-((R)-2,2,2-trifluoro-1-(3-(6-fluoro-7-(2-hydroxyethoxy)quinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)ethyl)pyrrolidin-3-yl)carbamateAusbeute 80 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel2×

Versuchsvorschrift

To a solution of 2-((2-(6-((R)-1-((S)-3-aminopyrrolidin-1-yl)-2,2,2-trifluoroethyl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-6-fluoro quinolin-7-yl)oxy)ethanol (125 mg, 0.255 mmol) in DMF (1.5 mL) was added a solution of (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 4-nitrophenyl carbonate (prepared according to procedures described in J. Med. Chem. 1999, 42, 3994-4000, 71.2 mg, 0.255 mmol) in DMF (1 mL). The reaction mixture was stirred at ambient temperature for 30 minutes. The reaction was partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc. The combined organic layers were washed with water and brine, dried and concentrated. The residue was purified by flash chromatography on silica gel (DCM:MeOH, 70:1 to 40:1) to give (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl ((S)-1-((R)-2,2,2-trifluoro-1-(3-(6-fluoro-7-(2-hydroxyethoxy)quinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)ethyl)pyrrolidin-3-yl)carbamate (131 mg, 80%). LCMS APCI (+) m/z 647 (M+H).

Aufarbeitung

  1. customThe reaction was partitioned between EtOAc and water
  2. extractionThe aqueous layer was extracted with EtOAc
  3. washThe combined organic layers were washed with water and brine
  4. customdried
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography on silica gel (DCM:MeOH, 70:1 to 40:1)

Quellen und Nachweise

ORD-Eintrag
ord-22de57705a584fbd841505fed5a0520b
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08889704B2

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