Hydrochloric Acid → HCID 178440905, compound

HRID 2410069Notes

Reaction equation

HRID 2410069 reaction equation
[CH:1]1([N:7]2[C:12]([OH:13])=[C:11]([C:14]([NH:16][CH2:17][C:18]([O:20]CC)=[O:19])=[O:15])[C:10](=[O:23])[NH:9][C:8]2=[O:24])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+].[Br:31][C:32]1[CH:37]=[C:36]([C:38]([CH3:41])([CH3:40])[CH3:39])[CH:35]=[CH:34][C:33]=1[CH2:42]Br.Cl>CN(C)C=O>[Br:31][C:32]1[CH:37]=[C:36]([C:38]([CH3:40])([CH3:39])[CH3:41])[CH:35]=[CH:34][C:33]=1[CH2:42][N:9]1[C:10](=[O:23])[C:11]([C:14]([NH:16][CH2:17][C:18]([OH:20])=[O:19])=[O:15])=[C:12]([OH:13])[N:7]([CH:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)[C:8]1=[O:24]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 453576952-Bromo-1-(bromomethyl)-4-tert-butylbenzeneHCID 68636133ethyl N-[(1-cyclohexyl-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycinate

Product 1

HCID 178440905HCID 178440905, compoundYield 7.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of ethyl N-[(1-cyclohexyl-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycinate (340 mg, 1.0 mmoles), pulv. potassium carbonate (740 mg, 5.35 mmoles) and 2-bromo-1-(bromomethyl)-4-(1,1-dimethylethyl)benzene (612 mg, 2.0 mmoles) in dimethylformamide (5 mL) was vigorously stirred at 100° C. for 3 hours. The mixture was poured into 1 molar hydrochloric acid and extracted with ethyl acetate (×2). The combined organic solutions were washed with 1 molar hydrochloric acid and evaporated. The residue was purified by flash chromatography (10-50% ethyl acetate in hexane), the required fractions evaporated, dissolved in ethanol (5 mL) and 1 molar sodium hydroxide solution (1.0 mL) and 6 molar sodium hydroxide (1.0 mL) added. The mixture was stirred overnight, acidified and extracted with ethyl acetate (×2), the combined extracts washed with 1 molar hydrochloric acid, dried and evaporated. Preparative HPLC (50-90% acetonitrile-water-0.1% TFA) gave the title compound (40 mg, 7.5%). 1H NMR (400 MHz, DMSO-d6) δ ppm 13.17 (br. s., 1 H), 10.14 (br. s., 1 H), 7.59 (d, J=1.52 Hz, 1H), 7.33 (dd, J=8.08, 1.52 Hz, 1 H), 6.92 (d, J=8.08 Hz, 1 H), 4.96 (s, 2 H), 4.65 (t, J=11.75 Hz, 1H), 4.13 (d, J=5.56 Hz, 2 H), 2.25 (q, J=11.54 Hz, 2 H), 1.79 (d, J=12.13 Hz, 2 H), 1.53-1.73 (m, 3 H), 1.20-1.38 (m, 11 H), 1.11 (q, 1 H)

Workup

  1. extractionextracted with ethyl acetate (×2)
  2. washThe combined organic solutions were washed with 1 molar hydrochloric acid
  3. customevaporated
  4. customThe residue was purified by flash chromatography (10-50% ethyl acetate in hexane)
  5. customthe required fractions evaporated
  6. dissolutiondissolved in ethanol (5 mL)
  7. addition1 molar sodium hydroxide solution (1.0 mL) and 6 molar sodium hydroxide (1.0 mL) added
  8. extractionextracted with ethyl acetate (×2)
  9. washthe combined extracts washed with 1 molar hydrochloric acid
  10. customdried
  11. customevaporated

Sources & evidence

ORD record
ord-e8373d3c5b38437fa131e68621c2d343
Source dataset
uspto-grants-2014_08
Patent number
US08815884B2

Reaction notes

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