Hydrazine hydrate (1:1) → HCID 73214301, compound

HRID 1398444Notes

Reaction equation

HRID 1398444 reaction equation
[CH3:1][C:2]1[N:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10](=[O:12])[N:9]([CH3:13])[C:8]1[CH:14]=[C:15]([O:22][CH2:23][C@@H:24]([N:29]3C(=O)C4C(=CC=CC=4)C3=O)[CH2:25][CH:26]([CH3:28])[CH3:27])[C:16]([C:18]([F:21])([F:20])[F:19])=[CH:17][C:7]2=1.O.NN>CCO>[NH2:29][C@@H:24]([CH2:25][CH:26]([CH3:28])[CH3:27])[CH2:23][O:22][C:15]1[C:16]([C:18]([F:20])([F:21])[F:19])=[CH:17][C:7]2[C:6]3[C:11](=[C:2]([CH3:1])[N:3]=[CH:4][CH:5]=3)[C:10](=[O:12])[N:9]([CH3:13])[C:8]=2[CH:14]=1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 86710424HCID 86710424, compound

Product 1

HCID 73214301HCID 73214301, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of (S)-2-(1-((4,6-dimethyl-5-oxo-9-(trifluoromethyl)-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)isoindoline-1,3-dione (50 mg, 0.019 mmol) in EtOH (4 mL) was added hydrazine hydrate (6.52 mg, 0.130 mmol). The reaction mixture was allowed to stir at 45° C. for 2 h. After cooling, the reaction mixture was concentrated under reduced pressure. The residue was purified by reverse phase HPLC (Symmetry C-18 column (19.0×250 mm) 7.0 micron; mobile phase A: Ammonium acetate in water; mobile phase B: acetonitrile; flow rate: 16.0 mL) to afford the (S)-8-((2-amino-4-methylpentyl)oxy)-4,6-dimethyl-9 (trifluoromethyl)benzo[c][2,7]naphthyridin-5(6H)-one (5 mg, 0.012 mmol, 64% yield) as an off-white solid. LC/MS (ESI) m/e 408.2 [(M+H)+, calcd for C21H25F3N3O2 408.2] LC/MS retention time (method B): tR=1.25 min. HPLC retention time (method A): tR=10.10 min HPLC retention time (method B): tR=10.69 min; 1H NMR (400 MHz, METHANOL-d4) δ ppm 8.66 (s, 1H), 8.63 (d, J=5.6 Hz, 1H), 8.22 (d, J=5.6 Hz, 1H), 7.19 (s, 1H), 4.42-4.38 (m, 1H), 4.28-4.20 (m, 1H), 3.83 (s, 3H), 3.58-3.49 (m, 1H), 3.11 (s, 3H), 1.90-1.82 (m, 1H), 1.68-1.62 (m, 1H), 1.58-1.53 (m, 1H), 1.10-1.00 (m, 6H).

Workup

  1. temperatureAfter cooling
  2. concentrationthe reaction mixture was concentrated under reduced pressure
  3. customThe residue was purified by reverse phase HPLC (Symmetry C-18 column (19.0×250 mm) 7.0 micron; mobile phase A: Ammonium acetate in water; mobile phase B: acetonitrile; flow rate: 16.0 mL)

Sources & evidence

ORD record
ord-3d36d0dd4de048e89979bfc86a5ea901
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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