Diisopropylethylamine → (S)-N-(1-(7-fluoro-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2-yl)ethyl)-9H-purin-6-amine

HRID 243472Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 243472
[F:1][C:2]1[CH:11]=[CH:10][C:9]2[N:12]=[C:13]([C@@H:14]([NH2:16])[CH3:15])[N:7]3[C:8]=2[C:3]=1[CH2:4][CH2:5][CH2:6]3.Cl[C:18]1[N:26]=[CH:25][N:24]=[C:23]2[C:19]=1[N:20]=[CH:21][N:22]2C1CCCCO1.CCN(C(C)C)C(C)C>C(O)CCC>[F:1][C:2]1[CH:11]=[CH:10][C:9]2[N:12]=[C:13]([C@@H:14]([NH:16][C:18]3[N:26]=[CH:25][N:24]=[C:23]4[C:19]=3[N:20]=[CH:21][NH:22]4)[CH3:15])[N:7]3[C:8]=2[C:3]=1[CH2:4][CH2:5][CH2:6]3

Komponenten

5

Edukt 3

HCID 81531DiisopropylethylamineHCID 977406-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 68157923(S)-1-(7-Fluoro-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2-yl)ethylamine

Produkt 1

HCID 178461922(S)-N-(1-(7-fluoro-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2-yl)ethyl)-9H-purin-6-amineAusbeute 58,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 2631-ButanolLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

A mixture of (5)-1-(7-fluoro-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-2-yl)ethylamine (48.5 mg, 0.221 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (52.9 mg, 0.221 mmol), and DIPEA (0.113 mL, 0.663 mmol) in n-butanol (1 mL) was stirred in a sealed vial at 90° C. for 16 h. After cooling to RT, volatiles were removed under reduced pressure. The residue was dissolved in MeOH (3 mL) and the resulting solution was cooled in an ice bath. HCl in isopropanol (1.25 M, 2 mL) was added and the mixture stirred at 0° C. for 1 h and then concentrated under reduced pressure. The residue was dissolved in MeOH and loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH and the product eluted with 0.5 M NH3 in MeOH, further purification by column chromatography (Si—PCC, gradient 2-14% 2M NH3/MeOH in DCM) afforded 398 as a white solid (43.4 mg, 58%). LCMS (Method J): RT 4.80 min [M+H]+ 338.2. 1H NMR ((CD3)2SO, 400 MHz): 12.81 (1H, bs), 8.23 (1H, s), 8.15 (1H, s), 7.96 (1H, d, J=7.8 Hz), 7.37 (1H, dd, J=8.8, 4.2 Hz), 6.92 (1H, dd, J=10.5, 8.8 Hz), 5.80 (1H, bs), 4.29-4.16 (2H, m), 2.87 (2H, t, J=6.1 Hz), 2.16-2.05 (2H, m), 1.68 (3H, d, J=6.8 Hz)

Aufarbeitung

  1. temperatureAfter cooling to RT
  2. customvolatiles were removed under reduced pressure
  3. dissolutionThe residue was dissolved in MeOH (3 mL)
  4. temperaturethe resulting solution was cooled in an ice bath
  5. additionHCl in isopropanol (1.25 M, 2 mL) was added
  6. stirringthe mixture stirred at 0° C. for 1 h
  7. concentrationconcentrated under reduced pressure
  8. dissolutionThe residue was dissolved in MeOH
  9. washThe cartridge was washed with MeOH
  10. washthe product eluted with 0.5 M NH3 in MeOH, further purification by column chromatography (Si—PCC, gradient 2-14% 2M NH3/MeOH in DCM)

Quellen und Nachweise

ORD-Eintrag
ord-d8133d55883b45f7aff0f778b0fbe100
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08653089B2

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