Acetic Acid → 5-ethyl-2-{4-[(1R,2R)-2-({[4-(1,2,4-oxadiazol-5-yl)benzyl]oxy}methyl)cyclopropyl]piperidin-1-yl}pyrimidine

HRID 1468851Notes

Reaction equation

HRID 1468851 reaction equation
[CH2:1]([C:3]1[CH:4]=[N:5][C:6]([N:9]2[CH2:14][CH2:13][CH:12]([C@H:15]3[CH2:17][C@H:16]3[CH2:18][O:19][CH2:20][C:21]3[CH:29]=[CH:28][C:24]([C:25]([NH2:27])=[O:26])=[CH:23][CH:22]=3)[CH2:11][CH2:10]2)=[N:7][CH:8]=1)[CH3:2].NO.CC(O)=O.CO[CH:38](OC)[N:39](C)C>O1CCOCC1>[CH2:1]([C:3]1[CH:4]=[N:5][C:6]([N:9]2[CH2:14][CH2:13][CH:12]([C@H:15]3[CH2:17][C@H:16]3[CH2:18][O:19][CH2:20][C:21]3[CH:22]=[CH:23][C:24]([C:25]4[O:26][N:39]=[CH:38][N:27]=4)=[CH:28][CH:29]=3)[CH2:11][CH2:10]2)=[N:7][CH:8]=1)[CH3:2]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 787HydroxylamineHCID 78373Dimethylformamide dimethyl acetalHCID 867177944-[({(1R,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]benzamide

Product 1

HCID 711368115-ethyl-2-{4-[(1R,2R)-2-({[4-(1,2,4-oxadiazol-5-yl)benzyl]oxy}methyl)cyclopropyl]piperidin-1-yl}pyrimidine

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of the product of step B (80 mg, 0.203 mmol) in N,N-dimethylformamide dimethyl acetal (2 mL) was stirred at 120° C. for 4 h. Upon cooling to RT, the solvent was removed under vacuum to leave a residue. The resulting residue was dissolved in 1,4-dioxane (1 mL) followed by the addition of NH2OH (0.016 mL of 50% solution in H2O, 0.243 mmol) and HOAc (0.5 mL). The reaction was stirred at 90° C. for 4 h before being cooled to RT. The reaction was quenched with a saturated aqueous solution of NaHCO3 and the layer was extracted with EtOAc (×3). The combined organic layers were washed with brine (1×), dried over MgSO4, filtered, and concentrated under vacuum to leave a residue which was purified by silica gel column chromatography (elution with 5:1 hexane:ethyl acetate) to give the title compound. MS (ESI) m/z 420 [M+H]+. GPR119 Human EC50: 5.5 nM

Workup

  1. customthe solvent was removed under vacuum
  2. customto leave a residue
  3. temperaturebefore being cooled to RT
  4. customThe reaction was quenched with a saturated aqueous solution of NaHCO3
  5. extractionthe layer was extracted with EtOAc (×3)
  6. washThe combined organic layers were washed with brine (1×)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under vacuum
  10. customto leave a residue which
  11. customwas purified by silica gel column chromatography (elution with 5:1 hexane:ethyl acetate)

Sources & evidence

ORD record
ord-0cfe44939a014a08a5bebc761d8082c6
Source dataset
uspto-grants-2015_04
Patent number
US09006228B2

Reaction notes

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