Hydrochloric Acid → Hydrochloric Acid

HRID 924890Notes

Reaction equation

HRID 924890 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%). HNMR (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-b0d21e40d1664bd09ba8fc35079ba306
Source dataset
uspto-grants-2016_03
Patent number
US09283229B2

Reaction notes

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