2-Piperidone → HCID 59242077, compound

HRID 1876226Notes

Reaction equation

HRID 1876226 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][C:2]1=[O:7].C([Li])CCC.Cl[CH2:14][C:15]1[N:24]=[C:23]([N:25]([C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=2)[CH3:26])[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[N:16]=1>C1COCC1>[CH3:34][O:33][C:30]1[CH:29]=[CH:28][C:27]([N:25]([CH3:26])[C:23]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[N:16]=[C:15]([CH2:14][N:1]3[CH2:6][CH2:5][CH2:4][CH2:3][C:2]3=[O:7])[N:24]=2)=[CH:32][CH:31]=1

Participants

5

Reactant 3

HCID 126652-PiperidoneHCID 11358914(2-Chloromethyl-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amineHCID 178418339Butyllithium

Product 1

HCID 59242077HCID 59242077, compoundYield 82.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To 2-piperidone (149 mg, 1.5 mmol) in THF (1 mL) at 0° C. was added n-butyllithium (2.5 M, 0.60 mL, 1.5 mmol) followed by a solution of (2-chloromethyl-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amine (150 mg, 0.43 mmol) in THF (1.5 mL). The reaction was heated to reflux for 2 h, cooled to room temperature, quenched with H2O and diluted with ether. The aqueous phase was extracted with ether (3×10 mL) The combined organic phases were washed with brine, dried (MgSO4), concentrated and purified by gradient MPLC (SiO2, 0-20% MeOH/CH2Cl2 with 0.1% NH4OH) to give 133 mg (82%) of the title compound as a yellow oil. 1H NMR (MeOH-d4) δ 7.73 (d, 1H), 7.52 (dd, 1H), 7.71 (d, 2H), 6.98-6.96 (m, 2H), 6.90 (d, 2H), 4.82 (s, 2H), 3.84 (s, 3H), 3.55 (s, 3H), 3.52 (m, 2H), 2.53 (m, 2H), 1.92-1.88 (m, 4H); LC-MS (ESI+; 377 ([M+H]+)).

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux for 2 h
  3. customquenched with H2O
  4. additiondiluted with ether
  5. extractionThe aqueous phase was extracted with ether (3×10 mL) The combined organic phases
  6. washwere washed with brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated
  9. custompurified by gradient MPLC (SiO2, 0-20% MeOH/CH2Cl2 with 0.1% NH4OH)

Sources & evidence

ORD record
ord-1eca105198744574bdab1ad5d27000ad
Source dataset
uspto-grants-2012_11
Patent number
US08309562B2

Reaction notes

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