Cesium carbonate → N-(5-chloro-2-nitrophenyl)-8-methyl-6-(pyridin-4-yl)-9-(tetrahydro-2H-pyran-4-yl)-9H-purin-2-amine

HRID 2074167Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2074167
[CH3:1][C:2]1[N:3]([CH:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[C:4]2[C:9]([N:10]=1)=[C:8]([C:11]1[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=1)[N:7]=[C:6]([NH2:17])[N:5]=2.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]>[Cl:83][C:81]1[CH:80]=[CH:79][C:78]([N+:84]([O-:86])=[O:85])=[C:77]([NH:17][C:6]2[N:5]=[C:4]3[C:9]([N:10]=[C:2]([CH3:1])[N:3]3[CH:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[C:8]([C:11]3[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=3)[N:7]=2)[CH:82]=1

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 98561242-Bromo-4-chloro-1-nitrobenzeneHCID 576126668-methyl-6-(pyridin-4-yl)-9-(tetrahydro-2H-pyran-4-yl)-9H-purin-2-amine

Produkt 1

HCID 57612643N-(5-chloro-2-nitrophenyl)-8-methyl-6-(pyridin-4-yl)-9-(tetrahydro-2H-pyran-4-yl)-9H-purin-2-amineAusbeute 21,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
170 °C

Versuchsvorschrift

To an oven-dried vial was added 8-methyl-6-(pyridin-4-yl)-9-(tetrahydro-2H-pyran-4-yl)-9H-purin-2-amine (56 mg, 0.18 mmol, 1 equiv.) in anhydrous toluene (1 mL), then freshly grounded cesium carbonate (82 mg, 0.25 mmol, 1.4 equiv.) with stirring at room temperature under Ar. After 10 min, Pd(OAc)2 (13.5 mg, 0.02 mmol, 0.1 equiv.), racemic BINAP (17 mg, 0.03 mmol, 0.15 equiv.) and 1-bromo-5-chloro-2-nitrobenzene (WO 02/053545 A1) (55 mg, 0.23 mmol, 1.3 equiv.) were added as solids. The vial was purged with Ar for 3 min, then closed and heated in a microwave oven at 170° C. for 2 h. 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 yellow solid (18 mg, 21% yield). 1H NMR (300 MHz, CDCl3+CD3OD) δ, ppm: 9.30 (s, 1H), 8.77 (br m, 2H), 8.64 (br m, 2H), 8.26 (d, J=8.9 Hz, H), 7.05 (d, J=7.9 Hz, 1H), 4.60-4.56 (m, 1H), 4.26-4.22 (m, 2H), 3.64 (app t, J=11.9 Hz, 2H), 2.94-2.90 (m, 2H), 2.76 (s, 3H), 1.91 (br d, J=11.2 Hz, 2H); MS (EI) m/z 466.3 (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-4bb3cc7240d5491c900f2f1020dd0db9
Quelldatensatz
uspto-grants-2011_04
Patentnummer
US07919490B2

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