1,1-Dichloroethane → Butyl-{3-[4-(tert-butylamino-methyl)-2-fluoro-phenyl]-imidazo[1,2-b]pyridazin-6-yl}-amine

HRID 870651Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 870651
[CH2:1]([NH:5][C:6]1[CH:7]=[CH:8][C:9]2[N:10]([C:12]([C:15]3[CH:22]=[CH:21][C:18]([CH:19]=O)=[CH:17][C:16]=3[F:23])=[CH:13][N:14]=2)[N:11]=1)[CH2:2][CH2:3][CH3:4].ClC(Cl)C.[C:28]([NH2:32])([CH3:31])([CH3:30])[CH3:29].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>>[CH2:1]([NH:5][C:6]1[CH:7]=[CH:8][C:9]2[N:10]([C:12]([C:15]3[CH:22]=[CH:21][C:18]([CH2:19][NH:32][C:28]([CH3:31])([CH3:30])[CH3:29])=[CH:17][C:16]=3[F:23])=[CH:13][N:14]=2)[N:11]=1)[CH2:2][CH2:3][CH3:4]

Komponenten

5

Edukt 4

HCID 63651,1-DichloroethaneHCID 6385Tert-ButylamineHCID 5049666Sodium triacetoxyborohydrideHCID 866963464-(6-Butylamino-imidazo[1,2-b]pyridazin-3-yl)-3-fluoro-benzaldehyde

Produkt 1

HCID 86696347Butyl-{3-[4-(tert-butylamino-methyl)-2-fluoro-phenyl]-imidazo[1,2-b]pyridazin-6-yl}-amineAusbeute 67 %

Versuchsvorschrift

A mixture of 4-(6-butylamino-imidazo[1,2-b]pyridazin-3-yl)-3-fluoro-benzaldehyde (120 mg, 0.40 mmol) and dichloroethane (DCE, 4 mL) was treated with tert-butyl amine (0.050 mL, 0.50 mmol) and the resulting reaction mixture was maintained at RT for 20 min. The reaction was then treated with sodium triacetoxyborohydride (170 mg, 0.80 mmol) and the resulting mixture was maintained until LCMS indicated complete consumption of the aldehyde. The reaction was quenched with saturated aqueous sodium bicarbonate, the layers were separated, and the aqueous layer was extracted with dichloromethane (3×20 mL). The combined organic layers were washed with water (20 mL) and brine (20 mL), then dried (MgSO4), filtered and concentrated to afford a residue that was purified by reverse phase HPLC to afford butyl-{3-[4-(tert-butylamino-methyl)-2-fluoro-phenyl]-imidazo[1,2-b]pyridazin-6-yl}-amine (98 mg, 67%) as a white solid: 1H NMR (400 MHz, METHANOL-d4) δ ppm 8.21 (dd, J=12.3, 1.5 Hz, 1H), 7.93 (dd, J=8.0, 1.7 Hz, 1H), 7.82 (s, 1H), 7.58 (d, J=9.7 Hz, 1H), 7.50 (t, J=8.0 Hz, 1H), 6.68 (d, J=9.7 Hz, 1H), 4.02 (s, 2H), 3.34 (t, J=7.2 Hz, 2H), 1.84 (s, 1H), 1.61-1.71 (m, 2H), 1.39-1.50 (m, 2H), 1.32 (s, 9H), 1.25-1.30 (m, 1H), 0.91-0.99 (m, 3H); LCMS (ESI) m/e 370.2 [(M+H)+, calcd for C21H29FN5 370.2].

Aufarbeitung

  1. customthe resulting reaction mixture
  2. temperaturethe resulting mixture was maintained until LCMS
  3. customconsumption of the aldehyde
  4. customThe reaction was quenched with saturated aqueous sodium bicarbonate
  5. customthe layers were separated
  6. extractionthe aqueous layer was extracted with dichloromethane (3×20 mL)
  7. washThe combined organic layers were washed with water (20 mL) and brine (20 mL)
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto afford a residue that
  12. customwas purified by reverse phase HPLC

Quellen und Nachweise

ORD-Eintrag
ord-d718cdb03501495c84bc8e18e1371c32
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08969565B2

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