Trifluoroacetic acid → 2-[4-(3,6-Dioxo-8-phenyl-2,6-dihydro-3H-9-oxa-1,2,3a-triaza-cyclopenta[a]naphthalen-7-yl)-phenyl]-2-methyl-propionitrile

HRID 1037331Notes

Reaction equation

HRID 1037331 reaction equation
[O:1]=[C:2]1[N:6]2[CH:7]=[CH:8][C:9]3[C:10](=[O:32])[C:11]([C:21]4[CH:26]=[CH:25][C:24]([C:27]([CH3:31])([CH3:30])[C:28]#[N:29])=[CH:23][CH:22]=4)=[C:12]([C:15]4[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=4)[O:13][C:14]=3[C:5]2=[N:4][N:3]1COCC[Si](C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[O:1]=[C:2]1[N:6]2[CH:7]=[CH:8][C:9]3[C:10](=[O:32])[C:11]([C:21]4[CH:22]=[CH:23][C:24]([C:27]([CH3:30])([CH3:31])[C:28]#[N:29])=[CH:25][CH:26]=4)=[C:12]([C:15]4[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=4)[O:13][C:14]=3[C:5]2=[N:4][NH:3]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 866710522-{-4-[3,6-Dioxo-8-phenyl-2-(2-trimethylsilanyl-ethoxymethyl)-2,6-dihydro-3H-9-oxa-1,2,3a-triaza-cyclopenta[a]naphthalen-7-yl]-phenyl}-2-methyl-propionitrile

Product 1

HCID 510301332-[4-(3,6-Dioxo-8-phenyl-2,6-dihydro-3H-9-oxa-1,2,3a-triaza-cyclopenta[a]naphthalen-7-yl)-phenyl]-2-methyl-propionitrileYield 47.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 2-{4-[3,6-dioxo-8-phenyl-2-(2-trimethylsilanyl-ethoxymethyl)-2,6-dihydro-3H-9-oxa-1,2,3a-triaza-cyclopenta[a]naphthalen-7-yl]-phenyl}-2-methyl-propionitrile (55 mg, 0.1 mmol) in DCM (2 mL), cooled in an ice bath, was added TFA (1.5 mL) at RT. After 16 h, the reaction mixture was evaporated to dryness, the resultant residue was dissolved in THF (3 mL) and benzyltrimethylammonium hydroxide solution (0.06 mL, 40% in MeOH) was added. The reaction mixture was stirred at RT for 1.5 h. EtOAc and water were added and the mixture was acidified by the addition of 1 M HCl (1 mL). The aqueous layer was extracted with EtOAc and the combined organic extracts were washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, EtOAc) to afford the title compound (20 mg, 47%) as a white solid. 1H NMR (400 MHz, CDCl3): δ 10.05 (s, 1H), 7.72 (d, J=7.3 Hz, 1H), 7.46-7.38 (m, 5H), 7.33-7.22 (m, 5H), 1.73 (s, 6H). LCMS (Method E): RT=4.22 min, [M+H]+=423.

Workup

  1. customthe reaction mixture was evaporated to dryness
  2. dissolutionthe resultant residue was dissolved in THF (3 mL)
  3. additionbenzyltrimethylammonium hydroxide solution (0.06 mL, 40% in MeOH) was added
  4. additionEtOAc and water were added
  5. additionthe mixture was acidified by the addition of 1 M HCl (1 mL)
  6. extractionThe aqueous layer was extracted with EtOAc
  7. washthe combined organic extracts were washed with brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-08819c55e2c14b138ed791eae40fca45
Source dataset
uspto-grants-2013_10
Patent number
US08546376B2

Reaction notes

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