Water → 2-(4-Fluoro-2-methyl-phenylamino)-1,6,7-trimethyl-1,8-dihydro-imidazo[4,5-h]isoquinolin-9-one

HRID 562430Notes

Reaction equation

HRID 562430 reaction equation
C(O[C:4](=O)[C:5]([C:10]1[CH:28]=[CH:27][C:13]2[N:14]=[C:15]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[CH3:26])[N:16]([CH3:17])[C:12]=2[C:11]=1[C:29]#[N:30])(C)[C:6](=O)[CH3:7])C.O.S(=O)(=O)(O)[OH:34].[OH-].[NH4+]>C(O)(=O)C>[F:25][C:22]1[CH:23]=[CH:24][C:19]([NH:18][C:15]2[N:16]([CH3:17])[C:12]3[C:11]4[C:29](=[O:34])[NH:30][C:6]([CH3:7])=[C:5]([CH3:4])[C:10]=4[CH:28]=[CH:27][C:13]=3[N:14]=2)=[C:20]([CH3:26])[CH:21]=1

Participants

6

Reactant 4

HCID 962WaterHCID 1118Sulfuric AcidHCID 14923Ammonium HydroxideHCID 668323242-[4-cyano-2-(4-fluoro-2-methyl-phenylamino)-3-methyl-3H-benzoimidazol-5-yl]-2-methyl-3-oxo-butyric acid ethyl ester

Product 1

HCID 668326292-(4-Fluoro-2-methyl-phenylamino)-1,6,7-trimethyl-1,8-dihydro-imidazo[4,5-h]isoquinolin-9-oneYield 70%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
100 °C

Procedure

To a glass scintillation vial equipped with a magnetic stir bar was added 2-[4-cyano-2-(4-fluoro-2-methyl-phenylamino)-3-methyl-3H-benzoimidazol-5-yl]-2-methyl-3-oxo-butyric acid ethyl ester (0.204 g, 0.483 mmol). A freshly prepared mixture of H2O (3.3 mL), glacial acetic acid (3.3 mL), and concentrated sulfuric acid (3.3 mL) at 60° C. was added to the vial. The vial was sealed with a screw cap and heated to 100° C. in a heating block. After 2.5 hours, the vial was allowed to cool to room temperature and stirred for an additional 12 h. The reaction mixture was then poured onto ice and neutralized by addition of concentrated ammonium hydroxide. The resulting precipitate was recovered by filtration and further purified by trituration with methanol to provide 2-(4-fluoro-2-methyl-phenylamino)-1,6,7-trimethyl-1,8-dihydro-imidazo[4,5-h]isoquinolin-9-one (0.1188 g, 70%) as a light gray solid. 1H NMR (400 MHz, DMSO-d6+TFA) δ 11.43 (br s, 1H), 10.49 (br s, 1H), 7.70-7.65 (m, 2H), 7.57 (dd, 1H, J1=5.5 Hz, J2=8.6 Hz), 7.37 (dd, 1H, J1=3.1 Hz, J2=9.8 Hz), 7.27 (td, 1H, J1=3.1 Hz, J2=11.7 Hz), 4.23 (s, 3H), 2.32 (app s, 6H), 2.23 (s, 3H); ESMS (m/z): found, 351.

Workup

  1. customTo a glass scintillation vial equipped with a magnetic stir bar
  2. additionwas added to the vial
  3. customThe vial was sealed with a screw
  4. customcap
  5. temperatureto cool to room temperature
  6. additionThe reaction mixture was then poured onto ice
  7. filtrationThe resulting precipitate was recovered by filtration
  8. customfurther purified by trituration with methanol

Sources & evidence

ORD record
ord-afcb439ab44a4511976b53baedce81c5
Source dataset
uspto-grants-2011_11
Patent number
US08067395B2

Reaction notes

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