Chloride → HCID 58962325, compound

HRID 1365735Notes

Reaction equation

HRID 1365735 reaction equation
[OH:1][C:2]1[C:7](=[O:8])N[C:5]([C:9]2([O:13][CH2:14][CH2:15][CH2:16]O)[CH2:12][CH2:11][CH2:10]2)=[N:4][C:3]=1[C:18]([O:20][CH2:21][CH3:22])=[O:19].[Cl-].[CH2:24](N(CC)CC)C.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1>[OH:1][C:2]1[C:7](=[O:8])[CH:24]2[CH2:16][CH2:15][CH2:14][O:13][C:9]3([CH2:12][CH2:11][CH2:10]3)[C:5]2=[N:4][C:3]=1[C:18]([O:20][CH2:21][CH3:22])=[O:19]

Participants

6

Reactant 4

HCID 312ChlorideHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 136000860HCID 136000860, compound

Product 1

HCID 58962325HCID 58962325, compoundYield 19%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A cold (0° C.) solution of ethyl 5-hydroxy-2-(1-(3-hydroxypropoxy)cyclobutyl)-6-oxo-1,6-dihydropyrimidine-4-carboxylate (3.0 g, 9.6 mmol) in tetrahydrofuran (25 mL) was treated with methanesulfony chloride (3.30 g, 29 mmol) followed by dropwise addition of triethylamine (4.7 mL, 33.6 mmol). The reaction was stirred for 16 hours at room temperature. The solvent was removed in vacuo and the mixture was dissolved in ethanol (50 mL) and dimethylformamide (25 mL). To the slurry was added potassium carbonate (1.36 g, 9.7 mmol) and the reaction was stirred at room temperature for 16 hours, followed by heating (80° C.) for 3 hours. The solvent was removed in vacuo. The crude product was diluted with ethyl acetate (50 mL) and washed with 1N hydrochloric acid (2×50 mL), extracted with ethyl acetate (2×25 mL) then brine ((50 mL). The solution was then dried (sodium sulfate), filtered and concentrated to give the title compound (0.534 g, 19%) as a brown solid. 1H NMR (500 MHz, CDCl3) δ: 10.64 (1H, br s), 4.45 (2H, q, J=7.0 Hz), 4.38 (2H, br), 3.91 (2H, t, J=5.0 Hz), 2.81 (2H, br), 2.36-2.44 (2H, m), 1.87-1.97 (1H, m), 1.82-1.86 (2H, m), 1.67-1.75 (1H, m), 1.43 (3H, t, J=7.2 Hz).

Workup

  1. customThe solvent was removed in vacuo
  2. dissolutionthe mixture was dissolved in ethanol (50 mL)
  3. stirringthe reaction was stirred at room temperature for 16 hours
  4. temperatureby heating (80° C.) for 3 hours
  5. customThe solvent was removed in vacuo
  6. additionThe crude product was diluted with ethyl acetate (50 mL)
  7. washwashed with 1N hydrochloric acid (2×50 mL)
  8. extractionextracted with ethyl acetate (2×25 mL)
  9. dry with materialThe solution was then dried (sodium sulfate)
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-e8820ec229fa4098a5e72c1b653e2f63
Source dataset
uspto-grants-2011_02
Patent number
US07893055B2

Reaction notes

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