Hydrochloric Acid → Hydrochloric Acid

HRID 401101Notes

Reaction equation

HRID 401101 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([C:7](=O)[CH2:8][C:9]2[CH:13]=[CH:12][S:11][CH:10]=2)=[CH:3][CH:2]=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:4]3[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=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 61056239HCID 61056239, compound2×

Product 2

HCID 313Hydrochloric AcidYield 6%HCID 56961515HCID 56961515, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 1-(pyridin-4-yl)-2-(thiophen-3-yl)ethanone (Intermediate 70) (180 mg, 0.89 mmol), 3-ethoxy-4-hydroxy-5-nitrobenzaldehyde (188 mg, 0.89 mmol), urea (160 mg, 2.70 mmol), conc. hydrochloric acid (0.5 mL) in ethanol (3 mL) was refluxed for 45 hours. The mixture was concentrated and purified by prep-HPLC (0.1% TFA as additive). To the residue was added HCl/MeOH (2 mL, 2 N) and concentrated to give Compound 136 as HCl salt (24.3 mg, yield 6%). 1HNMR (DMSO-d6 400 MHZ): δ 10.31 (brs, 1H), 9.03 (s, 1H), 8.72 (d, J=6.4 Hz, 2H), 7.71 (s, 1H), 7.61 (d, J=6.0 Hz, 2H), 7.45 (d, J=2.0 Hz, 1H), 7.30 (dd, J=4.8, 2.8 Hz, 1H), 7.17 (d, J=1.6 Hz, 1H), 7.02 (dd, J=2.8, 1.2 Hz, 1H), 6.50 (dd, J=5.2, 1.2 Hz, 1H), 5.32 (d, J=2.4 Hz, 1H), 4.05 (q, J=6.8 Hz, 2H), 1.34 (t, J=6.8 Hz, 3H). MS (ESI): m/z 438.9 [M+H]+.

Workup

  1. temperaturewas refluxed for 45 hours
  2. concentrationThe mixture was concentrated
  3. custompurified by prep-HPLC (0.1% TFA as additive)
  4. additionTo the residue was added HCl/MeOH (2 mL, 2 N)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-66d3fae149ae42fd92c28d3d190e8ffa
Source dataset
uspto-grants-2014_06
Patent number
US08741915B2

Reaction notes

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