Hydrochloric Acid → HCID 178525907, compound

HRID 2410063Notes

Reaction equation

HRID 2410063 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+].[F:31][C:32]1[CH:39]=[CH:38][C:35]([CH2:36]Br)=[C:34]([C:40]([F:43])([F:42])[F:41])[CH:33]=1.Cl>CC(N(C)C)=O>[CH:1]1([N:7]2[C:12]([OH:13])=[C:11]([C:14]([NH:16][CH2:17][C:18]([OH:20])=[O:19])=[O:15])[C:10](=[O:23])[N:9]([CH2:36][C:35]3[CH:38]=[CH:39][C:32]([F:31])=[CH:33][C:34]=3[C:40]([F:42])([F:41])[F:43])[C:8]2=[O:24])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 27375764-Fluoro-2-(trifluoromethyl)benzyl bromideHCID 68636133ethyl N-[(1-cyclohexyl-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycinate

Product 1

HCID 178525907HCID 178525907, compoundYield 38%

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 (750 mg, 5.35 mmoles) and 4-fluoro-2-trifluoromethylbenzyl bromide (455 mg, 1.77 mmoles) in dimethylacetamide (6 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 (3.0 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 hexane gave the title compound (184 mg, 38%). 1H NMR (400 MHz, DMSO-d6) δ ppm 13.10 (br. s., 1 H), 10.11 (br. s., 1 H), 7.67 (dd, J=9.09, 2.78 Hz, 1 H), 7.45 (ddd, J=8.40, 2.65 Hz, 1 H), 7.29 (dd, J=8.59, 5.31 Hz, 1 H), 5.13 (s, 2 H), 4.64 (t, J=12.00 Hz, 1 H), 4.13 (d, J=5.81 Hz, 2 H), 2.24 (q, 2 H), 1.78 (d, J=12.63 Hz, 2 H), 1.53-1.73 (m, 3 H), 1.28 (q, J=12.72 Hz, 2 H), 1.10 (q, J=12.63 Hz, 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 (3.0 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 hexane

Sources & evidence

ORD record
ord-9ba9d3b60f05453097d6bcb458aec3c5
Source dataset
uspto-grants-2014_08
Patent number
US08815884B2

Reaction notes

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