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

HRID 925589Notes

Reaction equation

HRID 925589 reaction equation
[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

Participants

7

Reactant 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

Product 1

HCID 509145924-(6-Bromo-8-(isobutylamino)imidazo[1,2-a]pyrazin-3-yl)-N-cyclopropylbenzamideYield 56.2%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
40 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-1d06c939423143a6a8c7cad6e9ca2fca
Source dataset
uspto-grants-2016_03
Patent number
US09284317B2

Reaction notes

Loading…