Hydrochloric Acid → HCID 178525904, compound

HRID 1042232Notes

Reaction equation

HRID 1042232 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]([F:42])([F:41])[C:33]1[CH:40]=[CH:39][C:36]([CH2:37]Br)=[CH:35][CH:34]=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]([CH2:37][C:36]3[CH:35]=[CH:34][C:33]([C:32]([F:31])([F:41])[F:42])=[CH:40][CH:39]=3)[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 1230621-(Bromomethyl)-4-(trifluoromethyl)benzeneHCID 68636133ethyl N-[(1-cyclohexyl-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)carbonyl]glycinate

Product 1

HCID 178525904HCID 178525904, compoundYield 37.5%

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-trifluoromethylbenzyl bromide (478 uL, 2.0 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 (×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 ethanol-water gave the title compound (176 mg, 37.5%). 1H NMR (400 MHz, DMSO-d6) δ ppm 13.10 (br. s., 1 H), 10.13 (br. s., 1 H), 7.69 (d, J=8.08 Hz, 2 H), 7.51 (d, J=8.08 Hz, 2 H), 5.07 (s, 2 H), 4.64 (t, J=12.13 Hz, 1 H), 4.13 (d, J=5.81 Hz, 2 H), 2.13-2.32 (m, 2 H), 1.78 (d, J=12.63 Hz, 2 H), 1.50-1.72 (m, 3 H), 1.28 (q, 2 H), 1.11 (q, J=13.22 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 ethanol-water

Sources & evidence

ORD record
ord-61d40384bb16444297830ba317e09e38
Source dataset
uspto-grants-2013_10
Patent number
US08557834B2

Reaction notes

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