Hydrazine hydrate (1:1) → HCID 49805152, compound

HRID 576126Notes

Reaction equation

HRID 576126 reaction equation
Cl[C:2]1[N:7]=[N:6][C:5]([C:8]2[CH:17]=[C:16]3[C:11]([CH:12]([C:25]4[CH:30]=[CH:29][C:28]([Cl:31])=[C:27]([Cl:32])[CH:26]=4)[CH2:13][N:14](C(OC(C)(C)C)=O)[CH2:15]3)=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.O.NN>C(O)C.[Pd]>[Cl:32][C:27]1[CH:26]=[C:25]([CH:12]2[C:11]3[C:16](=[CH:17][C:8]([C:5]4[N:6]=[N:7][CH:2]=[CH:3][CH:4]=4)=[CH:9][CH:10]=3)[CH2:15][NH:14][CH2:13]2)[CH:30]=[CH:29][C:28]=1[Cl:31]

Participants

5

Reactant 2

HCID 24654Hydrazine hydrate (1:1)2×HCID 87151241HCID 87151241, compound

Product 1

HCID 49805152HCID 49805152, compoundYield 77.7%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalyst2×HCID 702EthanolSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of tert-butyl 7-(6-chloropyridazin-3-yl)-4-(3,4-dichlorophenyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (259 mg, 0.52 mmol) in ethanol (15 mL) was added 10% palladium on carbon (80 mg) and hydrazine hydrate (128 mL, 2.60 mmol). The reaction mixture was heated at 75° C. for 1 hour under a nitrogen atmosphere. An additional quantity of hydrazine hydrate (128 mL, 2.60 mmol) was added and the reaction mixture heated at 75° C. for 3 hours 10% palladium on carbon (80 mg) was additionally added and the heating continued for another 2 hours. The reaction mixture was filtered through a celite pad and the filtrate concentrated in vacuo. The residue was dissolved in dichloromethane (5 mL) and treated with trifluoroacetic acid (10 mL) at ambient temperature for 1 hour. After concentration in vacuo the residue was partitioned between dichloromethane (50 mL) and 2N sodium hydroxide solution. The organic layer was washed with brine then dried over sodium sulfate. Concentration in vacuo gave the crude material which was purified by flash column chromatography ((95:5 to 50:50 ethyl acetate/ethyl acetate:methanol:ammonium hydroxide, 80:18:2 v/v) to give 4-(3,4-dichlorophenyl)-7-(pyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline (144 mg, 77%): [α]D=+19.2° (0.06, methanol): 1H NMR (CDCl3, 300 MHz) δ 9.15 (dd, J=5.0 Hz, 1.5 Hz, 1H), 7.90 (d, J=1.0 Hz, 1H), 7.85 (dd, J=8.5 Hz, 1.5 Hz, 1H), 7.77 (dd, J=8.3 Hz, 2.0 Hz, 1H), 7.54 (d, J=8.5 Hz, 1H), 7.37 (d, J=8.5 Hz, 1H), 7.24 (d, J=2.0 Hz, 1H), 7.04 (d, J=8.0 Hz, 1H), 6.99 (dd, J=8.3 Hz, 2.0 Hz, 1H), 4.15-4.11 (m, 3H), 3.44 (dd, J=12.8 Hz, 5.5 Hz, 1H), 3.10 (dd, J=13.0 Hz, 6.0 Hz, 1H), 1.95 (br s, 1H); ESI MS m/z 356 [M+H]+.

Workup

  1. additionwas additionally added
  2. filtrationThe reaction mixture was filtered through a celite pad
  3. concentrationthe filtrate concentrated in vacuo
  4. dissolutionThe residue was dissolved in dichloromethane (5 mL)
  5. additiontreated with trifluoroacetic acid (10 mL) at ambient temperature for 1 hour
  6. concentrationAfter concentration in vacuo the residue
  7. customwas partitioned between dichloromethane (50 mL) and 2N sodium hydroxide solution
  8. washThe organic layer was washed with brine
  9. dry with materialthen dried over sodium sulfate
  10. concentrationConcentration in vacuo
  11. customgave the crude material which
  12. customwas purified by flash column chromatography ((95:5 to 50:50 ethyl acetate/ethyl acetate:methanol:ammonium hydroxide, 80:18:2 v/v)

Sources & evidence

ORD record
ord-92c11d025f744957b0737a7576edb555
Source dataset
uspto-grants-2015_05
Patent number
US09034899B2

Reaction notes

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