Hydrochloric Acid → Hydrochloric Acid

HRID 401096Notes

Reaction equation

HRID 401096 reaction equation
[N:1]1[CH:6]=[CH:5][N:4]=[CH:3][C:2]=1[C:7](=O)[CH2:8][C:9]1[CH:13]=[CH:12][S:11][CH:10]=1.[CH2:15]([O:17][C:18]1[CH:19]=[C:20]([CH:23]=[C:24]([N+:27]([O-:29])=[O:28])[C:25]=1[OH:26])[CH:21]=O)[CH3:16].[NH2:30][C:31]([NH2:33])=[O:32].[ClH:34]>C(O)C>[CH2:15]([O:17][C:18]1[CH:19]=[C:20]([CH:21]2[C:8]([C:9]3[CH:13]=[CH:12][S:11][CH:10]=3)=[C:7]([C:2]3[CH:3]=[N:4][CH:5]=[CH:6][N:1]=3)[NH:33][C:31](=[O:32])[NH:30]2)[CH:23]=[C:24]([N+:27]([O-:29])=[O:28])[C:25]=1[OH:26])[CH3:16].[ClH:34]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 1176UreaHCID 5848783-Ethoxy-4-hydroxy-5-nitrobenzaldehydeHCID 62621723HCID 62621723, compound2×

Product 2

HCID 313Hydrochloric AcidYield 12.3%HCID 56961466HCID 56961466, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 1-(pyrazin-2-yl)-2-(thiophen-3-yl)ethanone (Intermediate 66) (30 mg, 0.15 mmol), 3-ethoxy-4-hydroxy-5-nitrobenzaldehyde (31 mg, 0.15 mmol) and urea (27 mg, 0.45 mmol) in 2 mL of ethanol was added 0.2 mL of conc. HCl, and was stirred at reflux overnight. The mixture was cooled and then purified by preparative HPLC (30-60% acetonitrile+0.15% trifluoroacetic acid in water, over 15 min.), the desired eluting solution was treated with HCl/MeOH (2 mL, 2M) and concentrated in vacuo to give Compound 131 as HCl salt (8.3 mg, yield 12.3%). 1H NMR (CD3OD 400 MHz): δ 8.69 (dd, J=1.6 Hz, 2.4 Hz, 1H), 8.48 (d, J=3.6 Hz, 1H), 8.17 (d, J=1.6 Hz, 1H), 7.60 (d, J=2.0 Hz, 1H), 7.37 (dd, J=3.2 Hz, 5.2 Hz, 1H), 7.18 (d, J=2.0 Hz, 1H), 7.02 (dd, J=1.2 Hz, 2.8 Hz, 1H), 6.66 (dd, J=1.2 Hz, 5.2 Hz, 1H), 5.42 (s, 1H), 4.11-4.06 (m, 2H), 1.42 (t, J=7.2 Hz, 3H); MS (ESI): m/z 440.2 [M+1]+.

Workup

  1. temperatureat reflux overnight
  2. temperatureThe mixture was cooled
  3. custompurified by preparative HPLC (30-60% acetonitrile+0.15% trifluoroacetic acid in water, over 15 min.)
  4. washthe desired eluting solution
  5. additionwas treated with HCl/MeOH (2 mL, 2M)
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-90cb840c9e874d3483f459a8d0732efc
Source dataset
uspto-grants-2014_06
Patent number
US08741915B2

Reaction notes

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