Hydrazine hydrate (1:1) → HCID 11631801, compound

HRID 883624Notes

Reaction equation

HRID 883624 reaction equation
[S:1]1[CH:5]=[CH:4][C:3]2[CH:6]=[C:7]([CH:10]3[C:19]4[C:14](=[CH:15][C:16]([C:20]5[N:21]=[N:22][C:23](Cl)=[CH:24][CH:25]=5)=[CH:17][CH:18]=4)[CH2:13][N:12]([CH3:27])[CH2:11]3)[CH:8]=[CH:9][C:2]1=2.O.NN>CO.[Pd]>[S:1]1[CH:5]=[CH:4][C:3]2[CH:6]=[C:7]([CH:10]3[C:19]4[C:14](=[CH:15][C:16]([C:20]5[N:21]=[N:22][CH:23]=[CH:24][CH:25]=5)=[CH:17][CH:18]=4)[CH2:13][N:12]([CH3:27])[CH2:11]3)[CH:8]=[CH:9][C:2]1=2

Participants

5

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 86603561HCID 86603561, compound

Product 1

HCID 11631801HCID 11631801, compoundYield 70.6%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a solution of the product obtained in Step B (2.02 g, 5.15 mmol) and hydrazine hydrate (8 mL) in MeOH (100 mL), was added 10% Pd/C (0.25 g). The reaction mixture was heated to reflux 8 h, then, the reaction mixture was filtered through a short pad of celite. The filtrate was concentrated to dryness under reduced pressure. The residue was diluted with CH2Cl2 (60 mL), then, washed with H2O (1×40 mL). The aqueous phase was extracted with additional amount of CH2Cl2 (3×20 mL). The combined organic phases were dried (Na2SO4) and concentrated to dryness under reduced pressure. The residue was purified using medium pressure chromatography (eluent: EtOAc/MeOH 9:1) to afford (+/−)-4-benzo[b]thiophen-5-yl-2-methyl-7-pyridazin-3-yl-1,2,3,4-tetrahydroisoquinoline (1.3 g, 71%, >99% AUC HPLC) as a white solid: 1H NMR (500 MHz, CDCl3) δ 9.14 (dd, J=1.6, 4.9 Hz, 1H), 7.94 (d, J=1.5 Hz, 1H), 7.84-7.79 (m, 2H), 7.71-7.67 (m, 2H), 7.51 (dd, J=8.6, 4.9 Hz, 1H), 7.44 (d, J=5.4 Hz, 1H), 7.28-7.26 (m, 1H), 7.20 (dd, J=8.3, 1.6 Hz, 1H), 7.06 (d, J=8.1 Hz, 1H), 4.46 (m, 1H), 3.90 (d, J=14.6 Hz, 1H), 3.76 (d, J=14.6 Hz, 1H), 3.15-3.10 (m, 1H), 2.71-2.65 (m, 1H), 2.48 (s, 3H); ESI-MS m/z 358 [M+H]+.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux 8 h
  3. filtrationthe reaction mixture was filtered through a short pad of celite
  4. concentrationThe filtrate was concentrated to dryness under reduced pressure
  5. additionThe residue was diluted with CH2Cl2 (60 mL)
  6. washwashed with H2O (1×40 mL)
  7. extractionThe aqueous phase was extracted with additional amount of CH2Cl2 (3×20 mL)
  8. dry with materialThe combined organic phases were dried (Na2SO4)
  9. concentrationconcentrated to dryness under reduced pressure
  10. customThe residue was purified

Sources & evidence

ORD record
ord-18643ece52a544589051940e18261133
Source dataset
uspto-grants-2012_08
Patent number
US08236796B2

Reaction notes

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