Sodium cyanoborohydride → methyl3-((((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(methyl)amino)cyclobutanecarboxylate

HRID 511581Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 511581
O=[C:2]1[CH2:5][CH:4]([C:6]([O:8][CH3:9])=[O:7])[CH2:3]1.[CH3:10][C:11]1([CH3:32])[O:15][C@@H:14]2[C@@H:16]([CH2:29][NH:30][CH3:31])[O:17][C@@H:18]([N:19]3[CH:27]=[N:26][C:25]4[C:20]3=[N:21][CH:22]=[N:23][C:24]=4[NH2:28])[C@@H:13]2[O:12]1.[BH3-]C#N.[Na+]>CO>[CH3:9][O:8][C:6]([CH:4]1[CH2:5][CH:2]([N:30]([CH2:29][C@@H:16]2[C@@H:14]3[C@@H:13]([O:12][C:11]([CH3:32])([CH3:10])[O:15]3)[C@H:18]([N:19]3[CH:27]=[N:26][C:25]4[C:20]3=[N:21][CH:22]=[N:23][C:24]=4[NH2:28])[O:17]2)[CH3:31])[CH2:3]1)=[O:7]

Komponenten

5

Edukt 3

HCID 5003444Sodium cyanoborohydrideHCID 110236419-((3aR,4R,6R,6aR)-2,2-Dimethyl-6-((methylamino)methyl)tetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-9H-purin-6-amineHCID 13992367Methyl 3-oxocyclobutane-1-carboxylate

Produkt 1

HCID 67774297methyl3-((((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(methyl)amino)cyclobutanecarboxylateAusbeute 63 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Versuchsvorschrift

A solution of methyl 3-oxocyclobutanecarboxylate (1.28 g crude), 9-((3aR,4R,6R,6aR)-2,2-dimethyl-6-((methylamino)methyl)tetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-9H-purin-6-amine (2.0 g, 6.25 mmol) (Townsend et al Org Lett 2009, 11, 2976-2679) and Ti(iPrO)4 (1.78 g, 6.25 mmol) in MeOH (50 mL) was stirred at 45° C. for 2 h, then NaCNBH3 (0.79 g, 12.50 mmol) was added. The reaction was stirred at RT overnight. The reaction was quenched with aq. sat. NaHCO3 (40 mL), filtered, extracted with DCM (40 mL×3), dried over Na2SO4 and concentrated. The residue was purified by SGC (DCM:MeOH=12:1) to obtain title compound (1.7 g, Yield 63%). 1H NMR (500 MHz, MeOD): δH 8.28-8.27 (m, 1H), 8.21 (s, 1H), 6.20-6.18 (m, 1H), 5.52 (dd, J=1.5, 6.0 Hz, 1H), 5.00 (dd, J=3.0, 6.0 Hz, 1H), 5.33 (brs, 1H), 3.65-3.63 (m, 3H), 2.77-2.55 (m, 4H), 2.19-2.11 (m, 5H), 2.00-1.82 (m, 2H), 1.59 (s, 3H), 1.38 (s, 3H) ppm; ESI-MS (m/z): 433.2[M+1]+.

Aufarbeitung

  1. customThe reaction was quenched with aq. sat. NaHCO3 (40 mL)
  2. filtrationfiltered
  3. extractionextracted with DCM (40 mL×3)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified by SGC (DCM:MeOH=12:1)

Quellen und Nachweise

ORD-Eintrag
ord-b7e98938fc3c4c0aba96a05d3082d8f5
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09096634B2

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