Water → 4-(6-Bromo-8-(isobutylamino)imidazo[1,2-a]pyrazin-3-yl)-N-cyclopropylbenzamide

HRID 1503360Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1503360
[Br:1][C:2]1[N:3]=[C:4]([NH:12][CH2:13][CH:14]([CH3:16])[CH3:15])[C:5]2[N:6]([C:8](I)=[CH:9][N:10]=2)[CH:7]=1.O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH:26]1([NH:29][C:30]([C:32]2[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=2)=[O:31])[CH2:28][CH2:27]1>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Br:1][C:2]1[N:3]=[C:4]([NH:12][CH2:13][CH:14]([CH3:16])[CH3:15])[C:5]2[N:6]([C:8]([C:35]3[CH:36]=[CH:37][C:32]([C:30]([NH:29][CH:26]4[CH2:27][CH2:28]4)=[O:31])=[CH:33][CH:34]=3)=[CH:9][N:10]=2)[CH:7]=1

Komponenten

7

Edukt 4

HCID 962Water2×HCID 62657Potassium Phosphate, TribasicHCID 2773359(4-(Cyclopropylcarbamoyl)phenyl)boronic acidHCID 715340446-Bromo-3-iodo-N-isobutylimidazo[1,2-a]pyrazin-8-amine

Produkt 1

HCID 509145924-(6-Bromo-8-(isobutylamino)imidazo[1,2-a]pyrazin-3-yl)-N-cyclopropylbenzamideAusbeute 56,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

To a stirred solution of (6-bromo-3-iodo-imidazo[1,2-a]pyrazin-8-yl)isobutyl-amine (74.20 g, 188 mmol) in dioxane (1300 mL) was subsequently added 130 mL water, 119 g tripotassium phosphate (563 mmol, 3 eq), 50.06 g [4-[(cyclopropylamino)carbonyl]phenyl]-boronic acid (244 mmol, 1.3 eq) and 7.42 g Pd(dppf)Cl2 (9 mmol, 0.05 eq) in one portion at rt under argon atmosphere. After stirring for 72 h at 40° C., the mixture was poured on 5 L water and the precipitate was filtered off and washed with water. The precipitate was taken up in DCM, washed with sat. sodium chloride solution, dried over sodium sulphate and after filtration the solvent was evaporated. Purification by flash chromatography (DCM/acetone 95:5) yielded 45.2 g (56.20%) 4-(6-bromo-8-isobutylamino-imidazo[1,2-a]pyrazin-3-yl)-N-cyclopropyl-benzamide: 1H-NMR (300 MHz, CDCl3): δ=7.90 (2H, d), 7.65 (1H, s), 7.58 (2H, d), 7.56 (1H, s), 6.32 (1H, s), 6.20 (1H, tr), 3.46 (2H, dd), 2.95 (1H, m), 2.01 (1H, m), 1.04 (6H, d), 0.92 (2H, m), 0.66 (2H, m) ppm.

Aufarbeitung

  1. customat rt
  2. filtrationthe precipitate was filtered off
  3. washwashed with water
  4. washwashed with sat. sodium chloride solution
  5. dry with materialdried over sodium sulphate
  6. filtrationafter filtration the solvent
  7. customwas evaporated
  8. customPurification by flash chromatography (DCM/acetone 95:5)

Quellen und Nachweise

ORD-Eintrag
ord-475f9717c4b143bd974523e99d5a96a0
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09212184B2

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