Acetic Anhydride → acetic acid 1-[2-(4-fluoro-2-methyl-phenylamino)-1,6-dimethyl-9-oxo-8,9-dihydro-1H-imidazo[4,5-h]isoquinolin-7-yl]-allyl ester

HRID 562432Notes

Reaction equation

HRID 562432 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:10]([CH3:28])[C:11]3[C:20]4[C:19](=[O:21])[NH:18][C:17]([CH:22]([OH:25])[CH:23]=[CH2:24])=[C:16]([CH3:26])[C:15]=4[CH:14]=[CH:13][C:12]=3[N:27]=2)=[C:4]([CH3:29])[CH:3]=1.C(N(CC)CC)C.[C:37](OC(=O)C)(=[O:39])[CH3:38].[Cl-].[NH4+]>CN(C1C=CN=CC=1)C.C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:10]([CH3:28])[C:11]3[C:20]4[C:19](=[O:21])[NH:18][C:17]([CH:22]([O:25][C:37](=[O:39])[CH3:38])[CH:23]=[CH2:24])=[C:16]([CH3:26])[C:15]=4[CH:14]=[CH:13][C:12]=3[N:27]=2)=[C:4]([CH3:29])[CH:3]=1

Participants

7

Reactant 4

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 668328842-(4-Fluoro-2-methyl-phenylamino)-7-(1-hydroxy-allyl)-1,6-dimethyl-1,8-dihydro-imidazo[4,5-h]isoquinolin-9-one

Product 1

HCID 66832334acetic acid 1-[2-(4-fluoro-2-methyl-phenylamino)-1,6-dimethyl-9-oxo-8,9-dihydro-1H-imidazo[4,5-h]isoquinolin-7-yl]-allyl esterYield 55%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a 25 mL round-bottom flask equipped with a magnetic stir bar was added 2-(4-fluoro-2-methyl-phenylamino)-7-(1-hydroxy-allyl)-1,6-dimethyl-1,8-dihydro-imidazo[4,5-h]isoquinolin-9-one (0.65 g, 1.7 mmol), THF (5 mL), triethylamine (0.52 g, 5.1 mmol) and acetic anhydride (0.22 g, 2.2 mmol). To the stirred suspension was then added DMAP (0.002 g, 0.02 mmol). After 1 hour, all reaction components were fully dissolved and the reaction was complete as determined by TLC analysis. To the reaction mixture was added saturated aqueous ammonium chloride (20 mL) and the solution was extracted with ethyl acetate (2×20 mL). The organic fractions were collected, washed with brine (1×20 mL), dried over sodium sulfate, and concentrated in vacuo. The crude product was further purified by silica gel chromatography, eluting with 2% methanol:DCM to provide acetic acid 1-[2-(4-fluoro-2-methyl-phenylamino)-1,6-dimethyl-9-oxo-8,9-dihydro-1H-imidazo[4,5-h]isoquinolin-7-yl]-allyl ester (0.404 g, 55%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6+TFA) δ ppm 11.35 (br s, 1H), 10.55 (br s, 1H), 7.74 (d, 1H, J=9.0 Hz), 7.70 (d, 1H, J=8.6 Hz), 7.56 (dd, 1H, J1=5.5 Hz, J2=8.6 Hz), 7.37-7.34 (m, 3H), 7.25 (td, 1H, J1=2.7 Hz, J2=8.2 Hz), 6.34 (app d, 1H, J=6.3 Hz), 6.17 (ddd, 1H, J1=6.3 Hz, J2=10.2 Hz, J3=16.8 Hz), 5.41 (app d, 1H, J=17.2 Hz), 5.33 (app d, 1H, J=10.2 Hz), 4.18 (s, 3H), 2.32 (s, 3H), 2.12 (s, 3H); ESMS (m/z): found, 435.

Workup

  1. customTo a 25 mL round-bottom flask equipped with a magnetic stir bar
  2. customall reaction components
  3. dissolutionwere fully dissolved
  4. extractionthe solution was extracted with ethyl acetate (2×20 mL)
  5. customThe organic fractions were collected
  6. washwashed with brine (1×20 mL)
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customThe crude product was further purified by silica gel chromatography
  10. washeluting with 2% methanol

Sources & evidence

ORD record
ord-7bcc58fb02884a0585f3f88f4b7b93a5
Source dataset
uspto-grants-2011_11
Patent number
US08067395B2

Reaction notes

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