Ammonium Chloride → 2-(2,6-Dichloro-phenylamino)-7-(1-hydroxy-allyl)-1,6-dimethyl-1,8-dihydro-imidazo[4,5-h]isoquinolin-9-one

HRID 562426Notes

Reaction equation

HRID 562426 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[NH:9][C:10]1[N:11]([CH3:27])[C:12]2[C:21]3[C:20](=[O:22])[NH:19][C:18]([CH:23]=[O:24])=[C:17]([CH3:25])[C:16]=3[CH:15]=[CH:14][C:13]=2[N:26]=1.[CH:28]([Mg]Br)=[CH2:29].[Cl-].[NH4+]>C1COCC1>[Cl:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=1[NH:9][C:10]1[N:11]([CH3:27])[C:12]2[C:21]3[C:20](=[O:22])[NH:19][C:18]([CH:23]([OH:24])[CH:28]=[CH2:29])=[C:17]([CH3:25])[C:16]=3[CH:15]=[CH:14][C:13]=2[N:26]=1

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 108622852-(2,6-Dichloro-phenylamino)-1,6-dimethyl-9-oxo-8,9-dihydro-1H-imidazo[4,5-h]isoquinoline-7-carbaldehydeHCID 178418507HCID 178418507, compound2×

Product 1

HCID 110912672-(2,6-Dichloro-phenylamino)-7-(1-hydroxy-allyl)-1,6-dimethyl-1,8-dihydro-imidazo[4,5-h]isoquinolin-9-oneYield 40%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a 50 mL round bottom flask equipped with a stir bar was added 2-(2,6-dichloro-phenylamino)-1,6-dimethyl-9-oxo-8,9-dihydro-1H-imidazo[4,5-h]isoquinoline-7-carbaldehyde (0.415 g, 1.03 mmol) and THF (12 mL). The reaction mixture was cooled to −78° C. To the stirred suspension was added vinylmagnesium bromide (5 mL, 1M in THF, 5 mmol) in one portion. The solution was allowed to gradually warm to −30° C. over 1 h. Additional vinylmagnesium bromide (3 mL, 1M in THF, 3 mmol) was added and the reaction mixture was further warmed to 0° C. over 1.5 h. The cold reaction mixture was poured into saturated aqueous ammonium chloride (50 mL) and extracted with EtOAc (3×50 mL). The organic fractions were collected, washed with brine (3×25 mL) and concentrated. The resulting solid was further purified by flash chromatography, eluting with EtOAc:Hexane (0-100%) to give 2-(2,6-dichloro-phenylamino)-7-(1-hydroxy-allyl)-1,6-dimethyl-1,8-dihydro-imidazo[4,5-h]isoquinolin-9-one (0.175 g, 40%) as a light yellow solid. 1H NMR (400 MHz, DMSO-d6+TFA) δ 10.43 (s, 1H), 7.77-7.75 (m, 4H), 7.59 (t, 1H, J=8.6 Hz), 6.06-5.98 (m, 1H) 5.42 (app d, 1H, J=5.5 Hz), 5.32 (app d, 1H, J=17.2 Hz), 5.16 (app d, 1H, J=10.2 Hz), 4.26 (s, 3H), 2.27 (s, 3H); ESMS (m/z): found, 429.

Workup

  1. customTo a 50 mL round bottom flask equipped with a stir bar
  2. temperatureto gradually warm to −30° C. over 1 h
  3. temperaturethe reaction mixture was further warmed to 0° C. over 1.5 h
  4. customThe cold reaction mixture
  5. extractionextracted with EtOAc (3×50 mL)
  6. customThe organic fractions were collected
  7. washwashed with brine (3×25 mL)
  8. concentrationconcentrated
  9. customThe resulting solid was further purified by flash chromatography
  10. washeluting with EtOAc

Sources & evidence

ORD record
ord-2cefd706105e41b980d37f7183f70e82
Source dataset
uspto-grants-2011_11
Patent number
US08067395B2

Reaction notes

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