Hydrochloric Acid → N-{[6-Hydroxy-1-{[3-(methyloxy)phenyl]methyl}-2,4-dioxo-3-(phenylmethyl)-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycine

HRID 2188760

Reaction equation

HRID 2188760 reaction equation
[OH:1][C:2]1[NH:7][C:6](=[O:8])[N:5]([CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:4](=[O:16])[C:3]=1[C:17]([NH:19][CH2:20][C:21]([O:23]CC)=[O:22])=[O:18].[CH3:26][O:27][C:28]1[CH:29]=[C:30]([CH:33]=[CH:34][CH:35]=1)[CH2:31]Br.C(=O)([O-])[O-].[Na+].[Na+].Cl>CN(C)C=O>[OH:1][C:2]1[N:7]([CH2:31][C:30]2[CH:33]=[CH:34][CH:35]=[C:28]([O:27][CH3:26])[CH:29]=2)[C:6](=[O:8])[N:5]([CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:4](=[O:16])[C:3]=1[C:17]([NH:19][CH2:20][C:21]([OH:23])=[O:22])=[O:18]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 40672073-Methoxybenzyl bromideHCID 178472773HCID 178472773, compound

Product 1

HCID 24831505N-{[6-Hydroxy-1-{[3-(methyloxy)phenyl]methyl}-2,4-dioxo-3-(phenylmethyl)-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycineYield 11%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of ethyl N-{[6-hydroxy-2,4-dioxo-3-(phenylmethyl)-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycinate (example 11a, 369 mg, 1.06 mmoles), 3-methoxybenzyl bromide (163 uL, 1.17 mmoles) and sodium carbonate (330 mg, 3.1 mmoles) in dimethylformamide (6.0 mL) was stirred under argon at 100° C. for 2.5 hours. The mixture was cooled, poured into 1 molar hydrochloric acid and extracted with ethyl acetate (×2). The ester was hydrolysed by stirring in a mixture of ethanol (3 mL) and 1 molar sodium hydroxide solution (3 mL) for 3 hours. The mixture was acidified and extracted with ethyl acetate. Purification by preparative HPLC (acetonitrile-water—0.1% TFA, 20-100%) and crystallization from ethanol-water gave the title compound (50 mg, 11%). 1H NMR (400 MHz, DMSO-d6) δ ppm 13.10 (br. s., 1 H), 10.12 (t, 1 H), 7.14-7.47 (m, 6 H), 6.69-6.97 (m, 3 H), 5.00 (s, 2 H), 5.03 (s, 2 H), 4.13 (d, J=5.56 Hz, 2 H), 3.71 (s, 3 H).

Workup

  1. temperatureThe mixture was cooled
  2. extractionextracted with ethyl acetate (×2)
  3. stirringby stirring in a mixture of ethanol (3 mL) and 1 molar sodium hydroxide solution (3 mL) for 3 hours
  4. extractionextracted with ethyl acetate
  5. customPurification
  6. customby preparative HPLC (acetonitrile-water—0.1% TFA, 20-100%) and crystallization from ethanol-water

Sources & evidence

ORD record
ord-6410022c4a1a42f69394bceca4b93388
Source dataset
uspto-grants-2012_12
Patent number
US08324208B2

Linked notes

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