Ammonium Hydroxide → 5-(2-Fluoro-4-iodophenylamino)imidazo[1,5-a]pyrazine-6-carboxamide

HRID 2064013Notes

Reaction equation

HRID 2064013 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[N:15]2[CH:16]=[N:17][CH:18]=[C:14]2[CH:13]=[N:12][C:11]=1[C:19]([OH:21])=O.C1C=CC2N(O)N=[N:28]C=2C=1.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C.[OH-].[NH4+]>C1COCC1.C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[N:15]2[CH:16]=[N:17][CH:18]=[C:14]2[CH:13]=[N:12][C:11]=1[C:19]([NH2:28])=[O:21]

Participants

8

Reactant 5

HCID 14923Ammonium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 591401265-(2-Fluoro-4-iodo-phenylamino)-imidazo[1,5-a]pyrazine-6-carboxylic acid

Product 1

HCID 591401585-(2-Fluoro-4-iodophenylamino)imidazo[1,5-a]pyrazine-6-carboxamideYield 16%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-(2-fluoro-4-iodo-phenylamino)-imidazo[1,5-a]pyrazine-6-carboxylic acid (64.0 mg, 0.16 mmol) in anhydrous THF (3.6 mL) was added HOBt (56.5 mg, 0.42 mmol, 2.6 eq), DIPEA (0.073 mL, 0.42 mmol, 2.6 mmol), and EDCI (67.8 mg, 0.35 mmol, 2.2 eq), and the reaction mixture was stirred at room temperature under N2 for 2 h. Concentrated aqueous ammonium hydroxide solution (0.50 mL) was added and the reaction mixture was stirred at room temperature for 20 h. The reaction mixture was diluted with ethyl acetate (50 mL) and washed with a saturated aqueous solution of ammonium chloride, water and brine. The organic layer was isolated and dried (Na2SO4), filtered, and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si-PPC, gradient 0 to 20% methanol in dichloromethane) to give an oil. Crystallization from DCM—ether—hexane afforded the title compound as a beige solid (9.9 mg, 16.0%). 1H NMR (MeOD, 400 MHz) δ ppm 8.74 (s, 1H), 7.86 (s, 1H), 7.79 (s, 1H), 7.62 (dd, J=10.4 Hz, 2.0 Hz, 1H), 7.48 (d, J=8.4 Hz, 1H), 6.59 (t, J=8.4 Hz, 1H); LCMS (method D1): RT=0.84 min, [M+H]+=398.

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 20 h
  2. washwashed with a saturated aqueous solution of ammonium chloride, water and brine
  3. customThe organic layer was isolated
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give an oil
  8. customCrystallization from DCM—ether—hexane

Sources & evidence

ORD record
ord-1420f5f256594d6b8dfc45408b9e3268
Source dataset
uspto-grants-2012_10
Patent number
US08288408B2

Reaction notes

Loading…