Hydrochloric Acid → HCID 178492041, compound

HRID 1042222Notes

Reaction equation

HRID 1042222 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+].[CH3:31][O:32][C:33]1[CH:34]=[C:35]([CH:38]=[C:39]([O:41][CH3:42])[CH:40]=1)[CH2:36]Br.Cl>CC(N(C)C)=O>[CH3:42][O:41][C:39]1[CH:38]=[C:35]([CH2:36][N:9]2[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]3[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]3)[C:8]2=[O:24])[CH:34]=[C:33]([O:32][CH3:31])[CH:40]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 12744903,5-Dimethoxybenzyl BromideHCID 68636133ethyl N-[(1-cyclohexyl-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycinate

Product 1

HCID 178492041HCID 178492041, compoundYield 41.2%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

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 (1.5 g, 11 mmoles) and 3,5-dimethoxybenzyl bromide (300 mg, 1.3 mmoles) in dimethylacetamide (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. The organic solution was 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 solution (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. Recrystallization from toluene gave the title compound (190 mg, 41%). 1H NMR (400 MHz, DMSO-d6) δ ppm 13.11 (s, 1 H), 10.15 (s, 1 H), 6.40 (s, 3 H), 4.92 (s, 2 H), 4.64 (t, J=11.87 Hz, 1 H), 4.09-4.17 (m, 2 H), 3.70 (s, 6 H), 2.26 (s, 2 H), 1.78 (d, J=12.63 Hz, 2 H), 1.62 (d, J=11.62 Hz, 3 H), 1.28 (q, J=13.05 Hz, 2 H), 1.06-1.17 (m, 1 H).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic solution was 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 solution (1.0 mL) added
  8. extractionextracted with ethyl acetate (×2)
  9. washthe combined extracts washed with 1 molar hydrochloric acid
  10. customdried
  11. customevaporated
  12. customRecrystallization from toluene

Sources & evidence

ORD record
ord-c09b753fa6bd47a7b33ae9bfa1715327
Source dataset
uspto-grants-2013_10
Patent number
US08557834B2

Reaction notes

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