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

HRID 2177960Notes

Reaction equation

HRID 2177960 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([O:16][CH3:17])[CH:11]=2)=[CH:4][CH:3]=1.[CH2:19]([O:21][C:22]1[CH:23]=[C:24]([CH:27]=[C:28]([N+:31]([O-:33])=[O:32])[C:29]=1[OH:30])[CH:25]=O)[CH3:20].[NH2:34][C:35]([NH2:37])=[O:36].Cl>CCO.CCOC(C)=O>[CH2:19]([O:21][C:22]1[CH:23]=[C:24]([CH:25]2[C:9]([C:10]3[CH:15]=[CH:14][CH:13]=[C:12]([O:16][CH3:17])[CH:11]=3)=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)[NH:37][C:35](=[O:36])[NH:34]2)[CH:27]=[C:28]([N+:31]([O-:33])=[O:32])[C:29]=1[OH:30])[CH3:20]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 1176UreaHCID 5848783-Ethoxy-4-hydroxy-5-nitrobenzaldehydeHCID 431599671-(4-Fluorophenyl)-2-(3-methoxyphenyl)ethanone2×

Product 1

HCID 668267914-(3-ethoxy-4-hydroxy-5-nitrophenyl)-6-(4-fluorophenyl)-5-(3-methoxyphenyl)-3,4-dihydropyrimidin-2(1H)-oneYield 20%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 1-(4-fluorophenyl)-2-(3-methoxyphenyl)ethanone (Intermediate 53) (200 mg, 0.82 mmol), 3-ethoxy-4-hydroxy-5-nitrobenzaldehyde (157 mg, 0.74 mmol), urea (134 mg, 2.23 mmol), concentrated HCl (0.06 mL, 0.74 mmol) in EtOH (5 mL) was refluxed overnight. Followed standard aqueous/EtOAc workup procedure, then purified by preparative HPLC to give Compound 108 (70 mg, yield 20%). 1H NMR (DMSO-d6 300 MHz): δ 10.29 (s, 1H), 8.77 (s, 1H), 7.55 (s, 1H), 7.45 (s, 1H), 7.27-7.24 (m, 2H), 7.20 (s, 1H), 7.15-7.09 (m, 2H), 6.99-6.94 (m, 1H), 6.59 (d, J=7.2 Hz, 1H), 6.39 (d, J=6.3 Hz, 2H), 5.22 (s, 1H), 4.07-4.05 (m, 2H), 3.49 (s, 3H), 1.33 (t, J=6.6 Hz, 3H); MS (ESI): m/z 479.9 [M+1]+.

Workup

  1. temperaturewas refluxed overnight
  2. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-acdb71fc8b4f4b2c8e421f6c39e9d136
Source dataset
uspto-grants-2015_06
Patent number
US09067893B2

Reaction notes

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