Acetonitrile → 1-(4-(tert-butyl)phenyl)-3-(3-((((3aR,4R,6R,6aR)-6-(4-((2,4-dimethoxybenzyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(methyl)amino)propyl)urea

HRID 2284545Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2284545
CS(O[CH2:6][CH2:7][CH2:8][NH:9][C:10]([NH:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]([CH3:22])([CH3:21])[CH3:20])=[CH:15][CH:14]=1)=[O:11])(=O)=O.C(N(CC)C(C)C)(C)C.[CH3:32][O:33][C:34]1[CH:63]=[C:62]([O:64][CH3:65])[CH:61]=[CH:60][C:35]=1[CH2:36][NH:37][C:38]1[C:39]2[CH:46]=[CH:45][N:44]([C@H:47]3[C@H:54]4[C@H:50]([O:51][C:52]([CH3:56])([CH3:55])[O:53]4)[C@@H:49]([CH2:57][NH:58][CH3:59])[O:48]3)[C:40]=2[N:41]=[CH:42][N:43]=1.C(#N)C.S([O-])(=O)(=O)C>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)(=O)C.C(OCC)C>[C:19]([C:16]1[CH:17]=[CH:18][C:13]([NH:12][C:10]([NH:9][CH2:8][CH2:7][CH2:6][N:58]([CH2:57][C@@H:49]2[C@@H:50]3[C@@H:54]([O:53][C:52]([CH3:56])([CH3:55])[O:51]3)[C@H:47]([N:44]3[C:40]4[N:41]=[CH:42][N:43]=[C:38]([NH:37][CH2:36][C:35]5[CH:60]=[CH:61][C:62]([O:64][CH3:65])=[CH:63][C:34]=5[O:33][CH3:32])[C:39]=4[CH:46]=[CH:45]3)[O:48]2)[CH3:59])=[O:11])=[CH:14][CH:15]=1)([CH3:22])([CH3:21])[CH3:20]

Komponenten

8

Edukt 5

HCID 6342AcetonitrileHCID 81531DiisopropylethylamineHCID 85257MethanesulfonateHCID 67818376HCID 67818376, VerbindungHCID 867023653-(3-(4-(Tert-butyl)phenyl)ureido)propyl methanesulfonate

Produkt 1

HCID 678145181-(4-(tert-butyl)phenyl)-3-(3-((((3aR,4R,6R,6aR)-6-(4-((2,4-dimethoxybenzyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(methyl)amino)propyl)ureaAusbeute 62 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 67553Tetrabutylammonium IodideKatalysator3×HCID 21584169Diethylether ethylacetateLösungsmittel

Reaktionsbedingungen

Temperatur
65 °C

Versuchsvorschrift

A mixture of 3-(3-(4-(tert-butyl)phenyl)ureido)propyl methanesulfonate (224 mg, 0.682 mmol), tetra-n-butylammonium iodide (252 mg, 0.682 mmol) and N,N-diisopropylethylamine (120 μL, 0.67 mmol) was treated with N-(2,4-dimethoxybenzyl)-7-((3aR,4R,6R,6aR)-2,2-dimethyl-6-((methylamino)methyl)tetrahydrofuro[3,4-d][1,3]-dioxol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (320 mg, 0.68 mmol) in acetonitrile (7.8 mL, 150 mmol) and the solution was heated at 65° C. After 16.5 h at 65° C., HPLC indicated the reaction was about 78-85% complete. An additional 60 mg of mesylate (in 0.4 mL CH3CN) and 67 mg of TBAI were added and continued heating for 7 h. The reaction mixture was cooled to room temperature and concentrated. The crude residue was purified by flash chromatography (60 g silica gel, 3-7% 7N NH3 in CH3OH/CH2Cl2) to yield the product contaminated with TBAI. The material was dissolved in 20 mL 1/1 ethyl acetate/ethyl ether and washed with three 10 mL portions of H2O. The organic phase was dried over Na2SO4, filtered and concentrated to yield the title compound (295 mg, 62%) as a foam: MS (ESI+) for C38H51N7O6 m/z 702.2 (M+H)+: (ESI−) for C38H51N7O6 m/z 700.3 (M−H)−; HPLC purity 96% (ret. time, 3.69 min).

Aufarbeitung

  1. temperaturecontinued heating for 7 h
  2. temperatureThe reaction mixture was cooled to room temperature
  3. concentrationconcentrated
  4. customThe crude residue was purified by flash chromatography (60 g silica gel, 3-7% 7N NH3 in CH3OH/CH2Cl2)
  5. customto yield the product
  6. washwashed with three 10 mL portions of H2O
  7. dry with materialThe organic phase was dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-2aeae2bb44184cbe88cc982c1b565b8b
Quelldatensatz
uspto-grants-2015_09
Patentnummer
US09145438B2

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