Ammonia → 2-(4-(5-amino-1H-indol-3-yl)-5,6-dihydropyridin-1(2H)-yl)ethanol

HRID 1186291Notes

Reaction equation

HRID 1186291 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]=[C:7]2[C:13]1[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][OH:21])[CH2:15][CH:14]=1)([O-])=O.O.NN.N.C(Cl)Cl>CO.[Ni]>[NH2:1][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]=[C:7]2[C:13]1[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][OH:21])[CH2:15][CH:14]=1

Participants

7

Reactant 4

HCID 222AmmoniaHCID 6344DichloromethaneHCID 24654Hydrazine hydrate (1:1)HCID 57791874HCID 57791874, compound

Product 1

HCID 577918722-(4-(5-amino-1H-indol-3-yl)-5,6-dihydropyridin-1(2H)-yl)ethanolYield 87%

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 887MethanolSolvent2×

Procedure

A solution of 2-(4-(5-nitro-1H-indol-3-yl)-5,6-dihydropyridin-1(2H)-yl)ethanol (0.225 g, 0.783 mmol) in dry methanol (5 mL) was treated with hydrazine hydrate (0.244 mL, 7.83 mmol), followed by Raney-nickel (0.1 g, 0.783 mmol) at room temperature. The resulting mixture was placed in a pre-heated oil bath and refluxed for 5 minutes (TLC basis, 2 M NH3 in MeOH:CH2Cl2, 1:9). The reaction was brought to room temperature, filtered through a Celite bed, and washed with methanol (3×10 mL). The combined methanol layer was evaporated and crude was purified by column chromatography (2 M NH3 in MeOH:CH2Cl2, 1:9) to obtain 2-(4-(5-amino-1H-indol-3-yl)-5,6-dihydropyridin-1(2H)-yl)ethanol (0.175 g, 87%) as a solid. 1H NMR (DMSO-d6) δ 10.59 (s, 1H), 7.15 (d, 1H, J=2.4 Hz), 7.05 (d, 1H, J=8.4 Hz), 6.99 (s, 1H), 6.48 (dd, 1H, J=1.8, 8.4 Hz), 5.96 (s, 1H), 4.48 (brs, 2H), 4.40 (t, 1H, J=5.4 Hz), 3.55 (q, 2H), 3.16-3.10 (m, 2H), 2.65 (t, 2H, J=5.7 Hz), 2.50-2.45 (m, 4H); ESI-MS (m/z, %): 258 (MH+, 30), 185 (100).

Workup

  1. customThe resulting mixture was placed in a pre-heated oil bath
  2. customwas brought to room temperature
  3. filtrationfiltered through a Celite bed
  4. washwashed with methanol (3×10 mL)
  5. customThe combined methanol layer was evaporated
  6. customcrude was purified by column chromatography (2 M NH3 in MeOH:CH2Cl2, 1:9)

Sources & evidence

ORD record
ord-809450b2b4644460acbdafa489bdd7e5
Source dataset
uspto-grants-2014_03
Patent number
US08673909B2

Reaction notes

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