Cesium carbonate → 2-(5-chloro-2-nitrophenylamino)-6-(pyridin-4-yl)-9-(tetrahydro-2H-pyran-4-yl)-7H-purin-8(9H)-one

HRID 2074159Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2074159
[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([NH:6][C:7](=[O:17])[N:8]2[CH:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)=[C:4]([C:18]2[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=2)[N:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.Br[C:77]1[CH:82]=[C:81]([Cl:83])[CH:80]=[CH:79][C:78]=1[N+:84]([O-:86])=[O:85]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2].CS(C)=O>[Cl:83][C:81]1[CH:80]=[CH:79][C:78]([N+:84]([O-:86])=[O:85])=[C:77]([NH:1][C:2]2[N:10]=[C:9]3[C:5]([NH:6][C:7](=[O:17])[N:8]3[CH:11]3[CH2:12][CH2:13][O:14][CH2:15][CH2:16]3)=[C:4]([C:18]3[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=3)[N:3]=2)[CH:82]=1

Komponenten

8

Edukt 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 98561242-Bromo-4-chloro-1-nitrobenzeneHCID 576126402-amino-6-(pyridin-4-yl)-9-(tetrahydro-2H-pyran-4-yl)-7H-purin-8(9H)-one

Produkt 1

HCID 576127192-(5-chloro-2-nitrophenylamino)-6-(pyridin-4-yl)-9-(tetrahydro-2H-pyran-4-yl)-7H-purin-8(9H)-oneAusbeute 11 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 679Dimethyl SulfoxideLösungsmittelHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
170 °C

Versuchsvorschrift

To an oven-dried vial was added 2-amino-6-(pyridin-4-yl)-9-(tetrahydro-2H-pyran-4-yl)-7H-purin-8(9H)-one (68 mg, 0.22 mmol, 1 equiv.) in anhydrous toluene (1 mL), then freshly grounded cesium carbonate (99.4 mg, 0.31 mmol, 1.4 equiv.) with stirring at room temperature under Ar. After 20 min, Pd(OAc)2 (15 mg, 0.02 mmol, 0.1 equiv.), racemic BINAP (20.5 mg, 0.03 mmol, 0.15 equiv.) and 1-bromo-5-chloro-2-nitrobenzene (WO 02/053545 A1) (67.6 mg, 0.29 mmol, 1.3 equiv.) were added as solids, followed by anhydrous DMSO (1 mL). The vial was purged with Ar for 3 min, then closed and heated in a microwave oven at 170° C. for 45 min. The reaction mixture was cooled to room temperature, diluted with ethyl acetate/methylene chloride, filtered through a Nylon 0.45 μm filter, and the filtrate was concentrated in vacuo. The resulting residue was purified using preparative TLC (silica gel, 7.5% methanol in methylene chloride) to give the desired product as a brown solid (11 mg, 11% yield). 1H NMR (300 MHz, CDCl3+CD3OD) δ, ppm: 9.13 (s, 1H), 8.63 (br m, 2H), 8.13 (d, J=8.9 Hz, 1H), 7.83 (br m, 2H), 6.91 (d, J=8.6 Hz, 1H), 4.70-4.50 (m, 1H), 4.10-4.03 (m, 2H), 3.51-3.43 (m, 2H), 2.68-2.65 (m, 2H), 1.71-1.66 (m, 2H); MS (EI) m/z 468.4 (MH)+.

Aufarbeitung

  1. customThe vial was purged with Ar for 3 min
  2. customclosed
  3. temperatureThe reaction mixture was cooled to room temperature
  4. additiondiluted with ethyl acetate/methylene chloride
  5. filtrationfiltered through a Nylon 0.45 μm
  6. filtrationfilter
  7. concentrationthe filtrate was concentrated in vacuo
  8. customThe resulting residue was purified

Quellen und Nachweise

ORD-Eintrag
ord-1d226e9874514b37a9d0950ceb6ef3dc
Quelldatensatz
uspto-grants-2011_04
Patentnummer
US07919490B2

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