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

HRID 562438Notes

Reaction equation

HRID 562438 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:10]([CH3:26])[C:11]3[C:20]4[C:19](=[O:21])[NH:18][C:17]([CH:22]=[O:23])=[C:16]([CH3:24])[C:15]=4[CH:14]=[CH:13][C:12]=3[N:25]=2)=[C:4]([CH3:27])[CH:3]=1.[CH:28]([Mg]Br)=[CH2:29]>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:10]([CH3:26])[C:11]3[C:20]4[C:19](=[O:21])[NH:18][C:17]([CH:22]([OH:23])[CH:28]=[CH2:29])=[C:16]([CH3:24])[C:15]=4[CH:14]=[CH:13][C:12]=3[N:25]=2)=[C:4]([CH3:27])[CH:3]=1

Participants

4

Reactant 2

HCID 866182842-(4-fluoro-2-methyl-phenylamino)-1,6-dimethyl-9-oxo-8,9-dihydro-1H-imidazo[4,5-h]isoquinoline-7-carbaldehydeHCID 178418507HCID 178418507, compound

Product 1

HCID 668328842-(4-Fluoro-2-methyl-phenylamino)-7-(1-hydroxy-allyl)-1,6-dimethyl-1,8-dihydro-imidazo[4,5-h]isoquinolin-9-oneYield 91%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a 1 L 3-neck round-bottom flask equipped with a magnetic stir-bar was added 2-(4-fluoro-2-methyl-phenylamino)-1,6-dimethyl-9-oxo-8,9-dihydro-1H-imidazo[4,5-h]isoquinoline-7-carbaldehyde (7.96 g, 21.9 mmole) and THF (260 mL). The resulting slurry was cooled to −78° C., and vinylmagnesium bromide (175 mL, 1.0 M in THF) was added dropwise over 30 minutes. The mixture was stirred at −78° C. for 2 hours, then warmed to −10° C. over 30 minutes and maintained at −10° C. for an additional 2 hours. The reaction was then quenched by addition of saturated aqueous ammonium chloride (200 mL), and extracted into EtOAc (2×200 mL). The organic layers were collected, washed with brine (2×100 mL), dried over sodium sulfate, and concentrated in vacuo to provide 2-(4-fluoro-2-methyl-phenylamino)-7-(1-hydroxy-allyl)-1,6-dimethyl-1,8-dihydro-imidazo[4,5-h]isoquinolin-9-one (7.8 g, 91%) as an orange-yellow solid, which was used without further purification. 1H NMR (400 MHz, DMSO-d6+TFA) δ 10.52 (br s, 1H), 10.38 (br s, 1H), 7.71 (app s, 2H), 7.55 (dd, 1H, J1=5.5 Hz, J2=8.6 Hz), 7.35 (dd, 1H, J1=3.1 Hz, J2=9.8 Hz), 7.24 (td, 1H, J1=9.1 Hz, J2=11.7 Hz), 6.02 (ddd, 1H, J1=5.9 Hz, J2=10.6 Hz, J3=17.2 Hz), 5.41 (app d, 1H, J=5.5 Hz), 5.33 (dt, 1H, J1=1.6 Hz, J2=17.2 Hz), 5.17 (dt, 1H, J1=1.2 Hz, J2=10.2 Hz), 4.19 (s, 3H), 2.29 (s, 3H), 2.26 (s, 3H); ESMS (m/z): 393 (M+1)+.

Workup

  1. customTo a 1 L 3-neck round-bottom flask equipped with a magnetic stir-bar
  2. temperaturewarmed to −10° C. over 30 minutes
  3. temperaturemaintained at −10° C. for an additional 2 hours
  4. customThe reaction was then quenched by addition of saturated aqueous ammonium chloride (200 mL)
  5. extractionextracted into EtOAc (2×200 mL)
  6. customThe organic layers were collected
  7. washwashed with brine (2×100 mL)
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8210b2d567e247a58e14e9bba8f4cc57
Source dataset
uspto-grants-2011_11
Patent number
US08067395B2

Reaction notes

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