Acetamide → 4-[({(1R,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]benzamide

HRID 1468850Notes

Reaction equation

HRID 1468850 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:28]=[CH:27][C:24]([C:25]#[N:26])=[CH:23][CH:22]=3)[CH2:11][CH2:10]2)=[N:7][CH:8]=1)[CH3:2].C(N)(=[O:31])C>C1COCC1.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:1]([C:3]1[CH:4]=[N:5][C:6]([N:9]2[CH2:10][CH2:11][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]([NH2:26])=[O:31])=[CH:27][CH:28]=3)[CH2:13][CH2:14]2)=[N:7][CH:8]=1)[CH3:2]

Participants

6

Reactant 2

HCID 178AcetamideHCID 711288064-[({(1R,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]benzonitrile

Product 1

HCID 867177944-[({(1R,2R)-2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]cyclopropyl}methoxy)methyl]benzamide

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

The product of step A (150 mg, 0.398 mmol), acetamide (101 mg, 1.71 mmol) and Pd(OAc)2 (13.4 mg, 0.02 mmol) in THF (4.5 mL) and H2O (1.5 mL) was heated at 65° C. for 24 h. The mixture was cooled to RT and diluted with H2O. The solution was extracted with EtOAc (×3). The combined organic layers were washed with brine (1×), dried over anhydrous MgSO4, filtered, and concentrated under vacuum to leave a residue which was purified by silica gel column chromatography (elution with 20:1 DCM:MeOH) to yield the desired compound. MS (ESI) m/z 395 [M+H]+.

Workup

  1. extractionThe solution was extracted with EtOAc (×3)
  2. washThe combined organic layers were washed with brine (1×)
  3. dry with materialdried over anhydrous MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customto leave a residue which
  7. customwas purified by silica gel column chromatography (elution with 20:1 DCM:MeOH)

Sources & evidence

ORD record
ord-26de9c116d0d41b09668c5ce616bdad5
Source dataset
uspto-grants-2015_04
Patent number
US09006228B2

Reaction notes

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