(S)-6-(1-Methylpiperidin-4-yl)-2-(2-oxo-4-(1-(2,3,5,6-tetrafluorophenyl)propan-2-ylamino)-1,2-dihydropyridin-3-yl)imidazo[4,5-f]isoindole-5,7(1H,6H)-dione → HCID 178461706, compound

HRID 69341Notes

Reaction equation

HRID 69341 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([N:8]2[C:16](=O)[C:15]3[CH:14]=[C:13]4[NH:18][C:19]([C:21]5[C:22](=[O:41])[NH:23][CH:24]=[CH:25][C:26]=5[NH:27][C@@H:28]([CH3:40])[CH2:29][C:30]5[C:35]([F:36])=[C:34]([F:37])[CH:33]=[C:32]([F:38])[C:31]=5[F:39])=[N:20][C:12]4=[CH:11][C:10]=3[C:9]2=[O:42])[CH2:4][CH2:3]1>C(O)(=O)C.[Zn]>[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([N:8]2[CH2:16][C:15]3[CH:14]=[C:13]4[N:18]=[C:19]([C:21]5[C:22](=[O:41])[NH:23][CH:24]=[CH:25][C:26]=5[NH:27][C@@H:28]([CH3:40])[CH2:29][C:30]5[C:31]([F:39])=[C:32]([F:38])[CH:33]=[C:34]([F:37])[C:35]=5[F:36])[NH:20][C:12]4=[CH:11][C:10]=3[C:9]2=[O:42])[CH2:4][CH2:3]1

Participants

4

Reactant 1

HCID 136340639(S)-6-(1-Methylpiperidin-4-yl)-2-(2-oxo-4-(1-(2,3,5,6-tetrafluorophenyl)propan-2-ylamino)-1,2-dihydropyridin-3-yl)imidazo[4,5-f]isoindole-5,7(1H,6H)-dione2×

Product 1

HCID 178461706HCID 178461706, compoundYield 13.8%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 176Acetic AcidSolvent

Procedure

To a solution of (S)-6-(1-methylpiperidin-4-yl)-2-(2-oxo-4-(1-(2,3,5,6-tetrafluorophenyl)propan-2-ylamino)-1,2-dihydropyridin-3-yl)imidazo[4,5-f]isoindole-5,7(1H,6H)-dione (Compound 27) (0.30 g, 0.51 mmol) in 50 mL of acetic acid was added zinc powder (0.64 g, 7.65 mmol). The mixture was heated to reflux for 16 h and filtered through Celite. Acetic acid was removed under vacuum and the residue was taken up with 10 mL of MeOH. Reverse phase chromatography purification yielded the title compound as a white solid (40 mg, 13.7%). 1H NMR δ (500 MHz, DMSO-d6) 13.03 (d, J=3.0 Hz, 1H), 11.25 (br s, 1H), 11.11 (dd, J=5, 13 Hz, 1H), 7.96 (s, 0.5H, conformational isomer), 7.81 (s, 0.5H), 7.77 (s, 0.5H), 7.80-7.65 (m, 1H), 7.61 (s, 0.5H), 7.41-7.31 (m, 1H), 6.16 (d, J=12.0 Hz, 1H), 4.48 (s, 2H), 4.29-4.14 (m, 1H), 4.12-3.96 (m, 1H), 3.20-3.02 (m, 2H), 2.90 (d, J=18 Hz, 2H), 2.23 (s, 3H), 2.07 (t, J=18 Hz, 2H), 1.94-1.75 (m, 2H), 1.78-1.64 (m, 2H), 1.42-1.29 (m, 3H). ESI MS: m/z 569.2 (M+1).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 16 h
  3. filtrationfiltered through Celite
  4. customAcetic acid was removed under vacuum
  5. customReverse phase chromatography purification

Sources & evidence

ORD record
ord-56be15b53a27454c915c3ccb50488825
Source dataset
uspto-grants-2014_09
Patent number
US08822500B2

Reaction notes

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