Hydrochloric Acid → HCID 67061145, compound

HRID 924900Notes

Reaction equation

HRID 924900 reaction equation
[CH2:1]([O:3][C:4]1[CH:13]=[C:12]([CH:14]=O)[CH:11]=[C:10]([N+:16]([O-:18])=[O:17])[C:5]=1[C:6]([O:8][CH3:9])=[O:7])[CH3:2].[C:19]1([C:25](=O)[CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[NH2:34][C:35]([NH2:37])=[O:36].Cl>C(O)C>[CH2:1]([O:3][C:4]1[CH:13]=[C:12]([CH:14]2[C:26]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[C:25]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[NH:37][C:35](=[O:36])[NH:34]2)[CH:11]=[C:10]([N+:16]([O-:18])=[O:17])[C:5]=1[C:6]([O:8][CH3:9])=[O:7])[CH3:2]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 1176UreaHCID 99482-PhenylacetophenoneHCID 86669339HCID 86669339, compound2×

Product 1

HCID 67061145HCID 67061145, compoundYield 58.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a mixture of methyl 2-ethoxy-4-formyl-6-nitrobenzoate (Intermediate 78) (100 mg, 0.4 mmol), 1,2-diphenylethanone (116 mg, 0.6 mmol) and urea (72 mg, 1.2 mmol) in ethanol (3 mL) was added conc. HCl (0.1 mL). Refluxed under N2 atmosphere overnight. Concentrated under reduced pressure, then purified by silica gel column chromatography (PE:EtOAc=10:1 to PE:EtOAc=1:1) to give methyl 2-ethoxy-6-nitro-4-(2-oxo-5,6-diphenyl-1,2,3,4-tetrahydropyrimidin-4-yl)benzoate (110 mg, yield 58%). This was taken up in ethanol (5 mL) and aq. NaOH (0.5 M, 2 mL, 1 mmol) was added. The mixture was stirred under N2 atmosphere at 60° C. for 5 hrs. The reaction mixture was acidified with conc. HCl (3 mL), and then extracted with a solution (DCM:i-propanol=10:1, 30 mL×2). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by prep-HPLC (0.1% TFA as additive) to give Compound 153 (58 mg, yield 55%). 1H NMR (DMSO-d6 400 MHz): δ 13.60 (s, 1H), 8.83 (s, 1H), 7.74 (s, 1H), 7.69 (s, 1H), 7.39 (s, 1H), 7.28-7.21 (m, 5H), 7.07-7.00 (m, 3H), 6.85 (d, J=6.8 Hz, 2H), 5.42 (d, J=2.4 Hz, 1H), 4.12-4.00 (m, 2H), 1.26 (t, J=7.0 Hz, 3H). MS (ESI): m/z 460.1[M+1]+.

Workup

  1. temperatureRefluxed under N2 atmosphere overnight
  2. concentrationConcentrated under reduced pressure
  3. custompurified by silica gel column chromatography (PE:EtOAc=10:1 to PE:EtOAc=1:1)

Sources & evidence

ORD record
ord-e3b336d74f9a41a4b68a58020942c0a0
Source dataset
uspto-grants-2016_03
Patent number
US09283229B2

Reaction notes

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