1,4-Dioxane → 2-(4-fluoro-2-methyl-phenylamino)-1,6-dimethyl-9-oxo-8,9-dihydro-1H-imidazo[4,5-h]isoquinoline-7-carbaldehyde

HRID 1863903Notes

Reaction equation

HRID 1863903 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:10]([CH3:25])[C:11]3[C:20]4[C:19](=[O:21])[NH:18][C:17]([CH3:22])=[C:16]([CH3:23])[C:15]=4[CH:14]=[CH:13][C:12]=3[N:24]=2)=[C:4]([CH3:26])[CH:3]=1.[O:27]1CCOCC1>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:10]([CH3:25])[C:11]3[C:20]4[C:19](=[O:21])[NH:18][C:17]([CH:22]=[O:27])=[C:16]([CH3:23])[C:15]=4[CH:14]=[CH:13][C:12]=3[N:24]=2)=[C:4]([CH3:26])[CH:3]=1

Participants

3

Reactant 2

HCID 312751,4-DioxaneHCID 668326292-(4-Fluoro-2-methyl-phenylamino)-1,6,7-trimethyl-1,8-dihydro-imidazo[4,5-h]isoquinolin-9-one

Product 1

HCID 866182842-(4-fluoro-2-methyl-phenylamino)-1,6-dimethyl-9-oxo-8,9-dihydro-1H-imidazo[4,5-h]isoquinoline-7-carbaldehydeYield 82%

Conditions

Temperature
100 °C

Procedure

To a 200 mL round-bottom flask equipped with a magnetic stir bar was added 2-(4-fluoro-2-methyl-phenylamino)-1,6,7-trimethyl-1,8-dihydro-imidazo[4,5-h]isoquinolin-9-one (1.3 g, 3.7 mmol) selenium dioxide (1.23 g, 11.0 mmol) and dioxane (100 mL). The flask was fitted with a reflux condenser and heated to 100° C. in an oil bath for 5 h. The flask was then cooled to room temperature and the mixture filtered through a plug of celite, washing with 10% MeOH/DCM. The filtrate was concentrated to dryness and the resulting brown solid further purified by trituration with cold DCM to give 2-(4-fluoro-2-methyl-phenylamino)-1,6-dimethyl-9-oxo-8,9-dihydro-1H-imidazo[4,5-h]isoquinoline-7-carbaldehyde (1.11 g, 82%) as a red-yellow solid. 1H NMR (400 MHz, DMSO-d6+TFA) δ 10.80 (br s, 1H), 10.70 (br s, 1H), 10.25 (s, 1H), 8.02 (d, 1H, J=8.8 Hz), 7.80 (d, 1H, J=8.8 Hz), 7.57 (dd, 1H, J1=5.5 Hz, J2=8.6 Hz), 7.35 (dd, 1H, J1=3.1 Hz, J2=9.8 Hz), 7.26 (td, 1H, J1=3.1 Hz, J2=8.6 Hz), 4.14 (s, 3H), 2.69 (s, 3H), 2.31 (s, 3H); ESMS (m/z): found, 365.

Workup

  1. customTo a 200 mL round-bottom flask equipped with a magnetic stir bar
  2. customThe flask was fitted with a reflux condenser
  3. temperatureThe flask was then cooled to room temperature
  4. filtrationthe mixture filtered through a plug of celite
  5. washwashing with 10% MeOH/DCM
  6. concentrationThe filtrate was concentrated to dryness
  7. customthe resulting brown solid further purified by trituration with cold DCM

Sources & evidence

ORD record
ord-5b204738f29641ab8c3e98bf88b9fbc2
Source dataset
uspto-grants-2009_12
Patent number
US07625880B2

Reaction notes

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