Methanol → HCID 66600266, Verbindung

HRID 1621657Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1621657
F[C:2]1[C:7]([C:8]2[N:16]=[C:15]([CH3:17])[N:14]=[C:13]3[C:9]=2[N:10]=[CH:11][N:12]3[CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][O:19]2)=[CH:6][CH:5]=[CH:4][N:3]=1.[NH2:24][C:25]1[CH:30]=[CH:29][C:28]([NH:31][C:32]([CH:34]2[CH2:36][CH2:35]2)=[O:33])=[CH:27][CH:26]=1.C[Si](N[Si](C)(C)C)(C)C.[Li].CO>C1COCC1.C(Cl)Cl>[CH3:17][C:15]1[N:14]=[C:13]2[C:9]([N:10]=[CH:11][N:12]2[CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][O:19]2)=[C:8]([C:7]2[C:2]([NH:24][C:25]3[CH:26]=[CH:27][C:28]([NH:31][C:32]([CH:34]4[CH2:35][CH2:36]4)=[O:33])=[CH:29][CH:30]=3)=[N:3][CH:4]=[CH:5][CH:6]=2)[N:16]=1

Komponenten

7

Edukt 4

HCID 887MethanolHCID 16227631N-(4-aminophenyl)cyclopropanecarboxamideHCID 57426343Lithium bis(trimethylsilyl)amideHCID 595484686-(2-fluoropyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine

Produkt 1

HCID 66600266HCID 66600266, VerbindungAusbeute 60,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A glass microwave reaction vessel was charged with 6-(2-fluoropyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (100 mg, 0.319 mmol) and N-(4-aminophenyl)cyclopropanecarboxamide (56.2 mg, 0.319 mmol, Enamine Ltd, Ukraine) in THF (5 mL), argon was bubbled through for 2 min, and the tube was sealed. The reaction mixture was cooled to 0° C. and lithium bis(trimethylsilyl)amine (1 N in THF, 1 mL, 1 mmol) was added dropwise. The red solution was stirred at 0° C. for 1 h and then warmed to room temperature. The mixture was quenched with saturated NH4Cl and extracted with EtOAc (3×). The organic extract was washed with satd NaCl and dried over Na2SO4. The solution was filtered and concentrated in vacuo. The crude material was purified by chromatography through a Redi-Sep pre-packed silica gel column (25 g) eluting with a gradient of 2% to 5% 2 M NH3.MeOH in DCM to give N-(4-(3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-ylamino)phenyl)cyclopropanecarboxamide (90 mg, 0.192 mmol, 60% yield) as a yellow solid. 1H NMR (400 MHz, d6-DMSO) δ 12.69 (s, 1H); 10.12 (s, 1H); 9.73 (dd, J=7.92, 1.86 Hz, 1H); 8.87 (s, 1H); 8.35 (dd, J=4.70, 1.76 Hz, 1H); 7.76 (d, J=9.00 Hz, 2H); 7.57 (d, J=8.80 Hz, 2H); 6.99 (dd, J=7.82, 4.69 Hz, 1H); 5.84 (dd, J=10.95, 1.76 Hz, 1H); 4.04 (d, J=12.63 Hz, 1H); 3.71-3.81 (m, 1H); 2.91 (s, 3H); 2.27-2.38 (m, 1H); 1.97-2.07 (m, 2H); 1.73-1.85 (m, 2H); 1.56-1.67 (m, 2H); 0.72-0.82 (m, 4H). m/z (ESI, +ve ion) 470 (M+H)+.

Aufarbeitung

  1. customA glass microwave reaction vessel
  2. customwas bubbled through for 2 min
  3. customthe tube was sealed
  4. temperaturewarmed to room temperature
  5. customThe mixture was quenched with saturated NH4Cl
  6. extractionextracted with EtOAc (3×)
  7. extractionThe organic extract
  8. washwas washed with satd NaCl
  9. dry with materialdried over Na2SO4
  10. filtrationThe solution was filtered
  11. concentrationconcentrated in vacuo
  12. customThe crude material was purified by chromatography through a Redi-Sep pre-packed silica gel column (25 g)
  13. washeluting with a gradient of 2% to 5% 2 M NH3

Quellen und Nachweise

ORD-Eintrag
ord-03553d4c5e244e42a794d575a46664a8
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08772480B2

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