Tetrahydrofuran → tert-butyl (aminosulfonyl)({(1S,2S,4R)-2-hydroxy-4-[(6-{[(1R,2S)-2-methoxy-2,3-dihydro-1H-inden-1-yl]amino}pyrimidin-4-yl)oxy]cyclopentyl}methyl)carbamate

HRID 1397557Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1397557
[NH2:1][S:2]([N:5]([CH2:13][C@@H:14]1[CH2:18][C@@H:17]([O:19][C:20]2[CH:25]=[C:24]([NH:26][C@@H:27]3[C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[CH2:29][C@@H:28]3[O:36][CH3:37])[N:23]=[CH:22][N:21]=2)[CH2:16][C@@H:15]1[O:38][Si](C(C)(C)C)(C)C)[C:6](=[O:12])[O:7][C:8]([CH3:11])([CH3:10])[CH3:9])(=[O:4])=[O:3].C1COCC1.F.N1C=CC=CC=1>N1C=CC=CC=1>[NH2:1][S:2]([N:5]([CH2:13][C@@H:14]1[CH2:18][C@@H:17]([O:19][C:20]2[CH:25]=[C:24]([NH:26][C@@H:27]3[C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[CH2:29][C@@H:28]3[O:36][CH3:37])[N:23]=[CH:22][N:21]=2)[CH2:16][C@@H:15]1[OH:38])[C:6](=[O:12])[O:7][C:8]([CH3:10])([CH3:11])[CH3:9])(=[O:3])=[O:4]

Komponenten

5

Edukt 3

HCID 8028TetrahydrofuranHCID 64774Pyridine, hydrofluoride (1:1)2×HCID 66797969tert-butyl (aminosulfonyl)({(1S,2S,4R)-2-{[tert-butyl(dimethyl)silyl]oxy}-4-[(6-{[(1R,2S)-2-methoxy-2,3-dihydro-1H-inden-1-yl]amino}-pyrimidin-4-yl)oxy]cyclopentyl}methyl)carbamate

Produkt 1

HCID 66797857tert-butyl (aminosulfonyl)({(1S,2S,4R)-2-hydroxy-4-[(6-{[(1R,2S)-2-methoxy-2,3-dihydro-1H-inden-1-yl]amino}pyrimidin-4-yl)oxy]cyclopentyl}methyl)carbamate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1049PyridineLösungsmittel

Reaktionsbedingungen

Temperatur
23 °C

Versuchsvorschrift

To a solution of tert-butyl (aminosulfonyl)({(1S,2S,4R)-2-{[tert-butyl(dimethyl)silyl]oxy}-4-[(6-{[(1R,2S)-2-methoxy-2,3-dihydro-1H-inden-1-yl]amino}-pyrimidin-4-yl)oxy]cyclopentyl}methyl)carbamate (331.5 mg, 0.0004094 mol) in THF (1.84 mL, 0.0228 mol) and pyridine (1.84 mL) at 0° C. was added pyridine hydrofluoride (0.25 mL, 0.0028 mol) dropwise. The mixture was allowed to slowly warm to 23° C. and stirred for 19 hours. To the reaction was added pyridine hydrofluoride (0.25 mL, 0.0028 mol) and the mixture was stirred an additional 6 hours. The reaction was quenched by the dropwise addition of saturated aqueous NaHCO3. The mixture was partitioned with additional saturated aqueous NaHCO3 and EtOAc, separated, and the aqueous was extracted with EtOAc (2×) and CH2Cl2 (2×). The combined organics were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography (30 to 70% EtOAc/hexanes) to collect 34.5 mg (15%) of the title compound. LC/MS: Rt=1.64 min, ES+ 550 (FA standard).

Aufarbeitung

  1. stirringthe mixture was stirred an additional 6 hours
  2. customThe reaction was quenched by the dropwise addition of saturated aqueous NaHCO3
  3. customThe mixture was partitioned with additional saturated aqueous NaHCO3 and EtOAc
  4. customseparated
  5. extractionthe aqueous was extracted with EtOAc (2×) and CH2Cl2 (2×)
  6. washThe combined organics were washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by flash chromatography (30 to 70% EtOAc/hexanes)
  11. customto collect 34.5 mg (15%) of the title compound

Quellen und Nachweise

ORD-Eintrag
ord-57332db41b4f450c88e04f4d4b0510e3
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08901136B2

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