Triethylamine → HCID 66588808, compound

HRID 1093054Notes

Reaction equation

HRID 1093054 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([CH:14]2[CH2:19][CH:18]([CH2:20]O)[CH2:17][N:16](/[C:22](=[CH:28]/[C:29]([O:31][CH2:32][CH3:33])=[O:30])/[C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:15]2)[NH:9][C:10](=[O:13])[C:11]=1[OH:12])=[O:5])[CH3:2].C(N(CC)CC)C.CS(Cl)(=O)=O.C([O-])([O-])=O.[K+].[K+]>C1COCC1.O>[CH2:26]([O:25][C:23](=[O:24])[C:22]([N:16]1[CH2:17][CH:18]2[CH2:19][CH:14]([C:8]3[N:9]([C:10](=[O:13])[C:11]([OH:12])=[C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])[N:7]=3)[CH2:20]2)[CH2:15]1)=[CH:28][C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH3:27]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 136061314HCID 136061314, compound

Product 1

HCID 66588808HCID 66588808, compoundYield 100.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
23 °C

Procedure

To diethyl 2-(3-(4-(ethoxycarbonyl)-5-hydroxy-6-oxo-1,6-dihydropyrimidin-2-yl)-5-(hydroxymethyl)piperidin-1-yl)maleate (1.05 g, 2.32 mmol) in THF at 0° C. was added triethylamine (0.975 mL, 6.99 mmol) and methanesulfonyl chloride (0.541 mL, 6.99 mmol). The reaction mixture was stirred at 23° C. for 3 hours. H2O (50 mL) was then added and the mixture was extracted with ethyl acetate (3×50 mL). The combined organic fractions were dried (MgSO4) and concentrated in vacuo. To the crude material dissolved in EtOH (40 mL) were added K2CO3 (0.643 g, 4.66 mmol) and H2O (1.7 mL). The reaction mixture was stirred at 23° C. for 36 hours. The solvent was removed in vacuo and the crude material was purified by silica gel column chromatography (Biotage flash chromatography system) using a gradient of ethyl acetate:methanol:AcOH (95:4:1) to (40:40:10) to afford 1.05 g (33% yield) of the title compound. 1H NMR (400 MHz, DMSO-D6) δ ppm 3.83-4.26 (7 H, m), 2.68-3.40 (6H, m), 2.02 (1 H, m), 1.79-1.89 (2 H, m), 1.07-1.31 (10 H, m). LCMS (+ESI, M+H+) m/z: 450.

Workup

  1. extractionthe mixture was extracted with ethyl acetate (3×50 mL)
  2. dry with materialThe combined organic fractions were dried (MgSO4)
  3. concentrationconcentrated in vacuo
  4. dissolutionTo the crude material dissolved in EtOH (40 mL)
  5. stirringThe reaction mixture was stirred at 23° C. for 36 hours
  6. customThe solvent was removed in vacuo
  7. customthe crude material was purified by silica gel column chromatography (Biotage flash chromatography system)

Sources & evidence

ORD record
ord-ed0c041ea7ed42ca994725383bae5e66
Source dataset
uspto-grants-2012_03
Patent number
US08129398B2

Reaction notes

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