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

HRID 562424Notes

Reaction equation

HRID 562424 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[C:24]([Cl:25])=[CH:23][CH:22]=[CH:21][C:20]=3[Cl: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]>C(O)(=O)C>[Cl:25][C:24]1[CH:23]=[CH:22][CH:21]=[C:20]([Cl:26])[C:19]=1[NH:18][C:15]1[N:16]([CH3:17])[C:12]2[C:11]3[C:29](=[O:34])[NH:30][C:6]([CH3:7])=[C:5]([CH3:4])[C:10]=3[CH:28]=[CH:27][C:13]=2[N:14]=1

Participants

5

Reactant 3

HCID 962WaterHCID 1118Sulfuric AcidHCID 120354962-[4-cyano-2-(2,6-dichloro-phenylamino)-3-methyl-3H-benzoimidazol-5-yl]-2-methyl-3-oxo-butyric acid ethyl ester

Product 1

HCID 99082472-(2,6-Dichloro-phenylamino)-1,6,7-trimethyl-1,8-dihydro-imidazo[4,5-h]isoquinolin-9-oneYield 46%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
100 °C

Procedure

A 25 mL round bottom flask was charged with 2-[4-cyano-2-(2,6-dichloro-phenylamino)-3-methyl-3H-benzoimidazol-5-yl]-2-methyl-3-oxo-butyric acid ethyl ester (0.258 g, 0.562 mmol) and a stir bar. Water (3 mL), glacial acetic acid (3 mL) and concentrated sulfuric acid (3 mL) were combined and added to the round bottom flask while still hot (60° C.). The flask was sealed with a plastic stopper and heated in an oil bath at 100° C. After 2 hours, the flask was removed from the oil bath and stirred at room temperature overnight. The clear solution was then poured onto ice and neutralized with concentrated ammonium hydroxide. The resulting precipitate was recovered by filtration, resuspended in methanol and filtered. The resulting solid was washed with methanol until the filtrate was colorless to provide 2-(2,6-dichloro-phenylamino)-1,6,7-trimethyl-1,8-dihydro-imidazo[4,5-h]isoquinolin-9-one (0.106 g, 46%) as a light gray solid, which was used without further purification. 1H NMR (400 MHz, DMSO-d6+TFA) δ 11.47 (s, 1H), 7.78-7.68 (m, 4H), 7.59 (t, 1H, J=8.6 Hz), 4.28 (2, 3H), 2.31 (s, 3H), 2.22 (s, 3H); ESMS (m/z): found, 387.

Workup

  1. additionadded to the round bottom flask while still hot (60° C.)
  2. customThe flask was sealed with a plastic stopper
  3. customthe flask was removed from the oil bath
  4. additionThe clear solution was then poured onto ice and neutralized with concentrated ammonium hydroxide
  5. filtrationThe resulting precipitate was recovered by filtration
  6. filtrationfiltered
  7. washThe resulting solid was washed with methanol until the filtrate

Sources & evidence

ORD record
ord-d096d849d6a14a0eba8e6f8d14cb06f5
Source dataset
uspto-grants-2011_11
Patent number
US08067395B2

Reaction notes

Loading…