Hydrochloric Acid → 3-Ethoxy-2-hydroxy-5-(2-oxo-5,6-diphenyl-1,2,3,4-tetrahydropyrimidin-4-yl)benzonitrile

HRID 924830Notes

Reaction equation

HRID 924830 reaction equation
[CH2:1]([O:3][C:4]1[C:5]([OH:14])=[C:6]([CH:9]=[C:10]([CH:12]=O)[CH:11]=1)[C:7]#[N:8])[CH3:2].[C:15]1([C:21](=O)[CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[NH2:30][C:31]([NH2:33])=[O:32].Cl>CCO.CO.CCOC(C)=O>[CH2:1]([O:3][C:4]1[C:5]([OH:14])=[C:6]([CH:9]=[C:10]([CH:12]2[C:22]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[C:21]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[NH:33][C:31](=[O:32])[NH:30]2)[CH:11]=1)[C:7]#[N:8])[CH3:2]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 1176UreaHCID 99482-PhenylacetophenoneHCID 866693323-Ethoxy-5-formyl-2-hydroxybenzonitrile

Product 1

HCID 513485173-Ethoxy-2-hydroxy-5-(2-oxo-5,6-diphenyl-1,2,3,4-tetrahydropyrimidin-4-yl)benzonitrileYield 45.7%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 3-ethoxy-5-formyl-2-hydroxybenzonitrile (285 mg, 1.5 mmol), 1,2-diphenylethanone (320 mg, 1.6 mmol), and urea (270 mg, 4.5 mmol) in anhydrous EtOH (5 mL) was added concentrated HCl solution (0.5 mL). The reaction mixture was refluxed overnight. TLC (EtOAc:MeOH=10:1) showed 40% of the starting materials were consumed. The reaction mixture was concentrated, and purified by column chromatography (EtOAc:MeOH=40:1) and preparative HPLC to afford Compound 69 as a yellow solid (280 mg, yield: 45.7%). 1H NMR (DMSO-d6 400 MHz TMS): δ 10.30 (s, 1H), 8.70 (d, J=1.2 Hz, 1H), 7.47 (s, 1H), 7.20-7.27 (m, 5H), 7.16 (d, J=1.6 Hz, 1H), 6.98-7.06 (m, 4H), 6.80-6.82 (m, 2H), 5.14 (d, J=2.4 Hz, 1H), 4.00-4.10 (m, 2H), 1.33 (t, J=7.2 Hz, 3H); MS (ESI): m/z 412.1 [M+1]+.

Workup

  1. temperatureThe reaction mixture was refluxed overnight
  2. customwere consumed
  3. concentrationThe reaction mixture was concentrated
  4. custompurified by column chromatography (EtOAc:MeOH=40:1) and preparative HPLC

Sources & evidence

ORD record
ord-3659d74f0d0e41d4bd49b712675296bd
Source dataset
uspto-grants-2016_03
Patent number
US09283229B2

Reaction notes

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