Hydrochloric Acid → 4-(3-ethoxy-4-hydroxy-5-nitrophenyl)-6-(4-fluorophenyl)-5-(thiophen-3-yl)-3,4-dihydropyrimidin-2(1H)-one

HRID 2177961Notes

Reaction equation

HRID 2177961 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)[CH2:9][C:10]2[CH:14]=[CH:13][S:12][CH:11]=2)=[CH:4][CH:3]=1.[CH2:16]([O:18][C:19]1[CH:20]=[C:21]([CH:24]=[C:25]([N+:28]([O-:30])=[O:29])[C:26]=1[OH:27])[CH:22]=O)[CH3:17].[NH2:31][C:32]([NH2:34])=[O:33].Cl>CCO.CCOC(C)=O>[CH2:16]([O:18][C:19]1[CH:20]=[C:21]([CH:22]2[C:9]([C:10]3[CH:14]=[CH:13][S:12][CH:11]=3)=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)[NH:34][C:32](=[O:33])[NH:31]2)[CH:24]=[C:25]([N+:28]([O-:30])=[O:29])[C:26]=1[OH:27])[CH3:17]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 1176UreaHCID 5848783-Ethoxy-4-hydroxy-5-nitrobenzaldehydeHCID 610540541-(4-Fluorophenyl)-2-(thiophen-3-yl)ethanone2×

Product 1

HCID 668265274-(3-ethoxy-4-hydroxy-5-nitrophenyl)-6-(4-fluorophenyl)-5-(thiophen-3-yl)-3,4-dihydropyrimidin-2(1H)-oneYield 27%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 1-(4-fluorophenyl)-2-(thiophen-3-yl)ethanone (Intermediate 54) (100 mg, 0.45 mmol), 3-ethoxy-4-hydroxy-5-nitrobenzaldehyde (87 mg, 0.41 mmol), urea (74 mg, 1.24 mmol), concentrated HCl (0.04 mL, 0.41 mmol) in EtOH (5 mL) was refluxed overnight. Followed standard aqueous/EtOAc workup procedure, then purified by preparative HPLC to give Compound 109 (50 mg, yield 27%). 1H NMR (DMSO-d6 400 MHz): δ 10.30 (s, 1H), 8.77 (s, 1H), 7.58 (s, 1H), 7.49 (s, 1H), 7.34-7.30 (m, 2H), 7.27 (s, 1H), 7.23-7.18 (m, 3H), 6.88 (s, 1H), 6.27 (d, J=5.2 Hz, 1H), 5.21 (d, J=2.8 Hz, 1H), 4.13-4.06 (m, 2H), 1.36 (t, J=6.8 Hz, 3H); MS (ESI): m/z 456.0 [M+1]+.

Workup

  1. temperaturewas refluxed overnight
  2. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-ca264160014e4cdb97527d523072cc9e
Source dataset
uspto-grants-2015_06
Patent number
US09067893B2

Reaction notes

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