Triethylamine → HCID 136380214, compound

HRID 1093109Notes

Reaction equation

HRID 1093109 reaction equation
[C:1]([O:9][C:10]1[C:15](=[O:16])[NH:14][C:13]([C:17]2([O:25][CH2:26][CH2:27][O:28]OC(=O)C3C=CC=CC=3)[CH2:22][CH2:21][CH:20]([CH2:23][OH:24])[CH2:19][CH2:18]2)=[N:12][C:11]=1[C:38]([O:40][CH2:41][CH3:42])=[O:39])(=[O:8])C1C=CC=CC=1.C(N([CH2:48][CH3:49])CC)C.[CH3:50][S:51](Cl)(=[O:53])=[O:52].C([O:58][CH2:59][CH3:60])(=O)C>C1COCC1>[C:1]([O:9][C:10]1[C:15](=[O:16])[NH:14][C:13]([C:17]2([O:25][CH2:26][CH2:27][O:28][C:59](=[O:58])[C:60]3[CH:49]=[CH:48][CH:15]=[CH:10][CH:11]=3)[CH2:18][CH2:19][CH:20]([CH2:23][O:24][S:51]([CH3:50])(=[O:53])=[O:52])[CH2:21][CH2:22]2)=[N:12][C:11]=1[C:38]([O:40][CH2:41][CH3:42])=[O:39])(=[O:8])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 8857Ethyl AcetateHCID 31297Methanesulfonyl chloride2×HCID 136380217HCID 136380217, compound

Product 1

HCID 136380214HCID 136380214, compoundYield 99%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Under N2, to a cold (ice-bath), stirred solution of ethyl 5-(benzoyloxy)-2-(1-(2-(benzoylperoxy)ethoxy)-4-(hydroxymethyl)cyclohexyl)-6-oxo-1,6-dihydropyrimidine-4-carboxylate (1.13 g, 2.001 mmol) in THF (10 mL) was added, triethylamine (0.279 mL, 2.00 mmol), followed by methane sulfonylchloride (0.156 mL, 2.001 mmol), and the mixture stirred at room temperature overnight. Additional triethylamine (50 mg, 0.5 mmol) and methane sulfonylchloride (40 uL, 0.5 mmol) were added and the mixture stirred at room temperature 2 h. The mixture was diluted with ethyl acetate (15 mL) and washed with water followed by brine, then dried (Na2SO4) and concentrated to provide ethyl 5-(benzoyloxy)-2-(1-(2-(benzoyloxy)ethoxy)-4-((methylsulfonyloxy)methyl)cyclohexyl)-6-oxo-1,6-dihydropyrimidine-4-carboxylate (1.27 g, 1.976 mmol, 99%) as a tan foam: HPLC: retention time=3.00 min (area percent=71%); LCMS: m/z 643 (M+H). To a solution of this compound (1.27 g, 1.98 mmol) in DMF (10 mL) was added cesium carbonate (0.644 g, 1.98 mmol) and the mixture stirred for 6 h at 60° C. in an oil bath under N2. The mixture was concentrated and the residue taken up in ethyl acetate (20 mL), washed with 1M-aq. K2CO3, water, followed by brine, then dried (Na2SO4), filtered and concentrated to provide 930 mg of a light brown crystalline powder. This was purified by silica gel column chromatography (60 g SiO2, 5-10% ethyl acetate/CH2Cl2) to provide the title compound (382 mg, 0.699 mmol, 35% yield) as an off-white crystalline solid: HPLC: retention time=3.24 min (area percent=94%); TLC: RF 0.6 (10% ethyl acetate/CH2Cl2): LCMS: m/z 547 (M+H); 1H NMR (500 MHz, CDCl3) δ ppm 1.19 (3H, t, J=7.0 Hz), 1.66-1.79 (2H, m), 1.89-2.01 (2H, m), 2.07-2.16 (2H, m), 2.17-2.27 (2H, m), 2.46 (1H, brs), 4.00 (2H, t, J=5.2 Hz), 4.09 (2H, d, J=3.7 Hz), 4.27 (2H, q, J=7.0 Hz), 4.62 (2H, t, J=5.3 Hz), 7.43 (2H, t, J=7.8 Hz), 7.49 (2H, t, J=7.8 Hz), 7.55 (1H, t, J=7.5 Hz), 7.63 (1H, t, J=7.5 Hz), 8.06 (2H, dd, J=8.4, 1.1 Hz), 8.19 (2H, dd, J=8.4, 1.1 Hz); 13C NMR (126 MHz, CDCl3) δ ppm 14.0, 23.3, 27.7, 30.9, 54.2, 62.1, 62.2, 64.8, 78.0, 128.4, 128.6, 128.7, 129.8, 130.5, 130.7, 133.0, 134.0, 136.6, 140.7, 159.9, 161.2, 162.9, 163.8, 166.7.

Workup

  1. additionwas added
  2. stirringthe mixture stirred at room temperature 2 h
  3. washwashed with water
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-e60b1d02d9f54cd3a959b666a8725d83
Source dataset
uspto-grants-2012_03
Patent number
US08129398B2

Reaction notes

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