Triphenylphosphine → 1-{3-[(4-Chloro-6-methoxyquinazolin-7-yl)oxy]propyl}-4-methylpiperazin-2-one

HRID 1785143Notes

Reaction equation

HRID 1785143 reaction equation
CC(OC(/N=N/C(OC(C)(C)C)=O)=O)(C)C.[Cl:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([OH:30])=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1.O[CH2:32][CH2:33][CH2:34][N:35]1[CH2:40][CH2:39][N:38]([CH3:41])[CH2:37][C:36]1=[O:42].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCl>[Cl:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:32][CH2:33][CH2:34][N:35]3[CH2:40][CH2:39][N:38]([CH3:41])[CH2:37][C:36]3=[O:42])=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1

Participants

6

Reactant 4

HCID 11776Triphenylphosphine2×HCID 6034084Di-tert-butyl diazene-1,2-dicarboxylate2×HCID 450995871-(3-Hydroxypropyl)-4-methylpiperazin-2-oneHCID 1357422514-Chloro-6-methoxyquinazolin-7-ol

Product 1

HCID 866015631-{3-[(4-Chloro-6-methoxyquinazolin-7-yl)oxy]propyl}-4-methylpiperazin-2-oneYield 50.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Di-tert-butylazodicarboxylate (393 mg, 1.71 mmol) was added portionwise, at room temperature, to a stirred suspension of 4-chloro-6-methoxyquinazolin-7-ol, (300 mg, 1.42 mmol), 1-(3-hydroxypropyl)-4-methylpiperazin-2-one (270 mg, 1.57 mmol) and triphenylphosphine (522 mg, 1.99 mmol) in dichloromethane (10 ml). The reaction was stirred 1 hr before adding further di-tert-butylazodicarboxylate (393 mg) and triphenylphosphine (522 mg) and stirring for a further 1 hr. The resulting reaction solution was purified by column chromatography on silica using increasing concentrations of methanol in dichloromethane as eluent to give 1-{3-[(4-chloro-6-methoxyquinazolin-7-yl)oxy]propyl}-4-methylpiperazin-2-one (260 mg, 50%) as a pale yellow solid; NMR Spectrum:(DMSOd6) 2.06 (quintet, 2H), 2.20 (s, 3H), 2.60 (t, 2H), 2.91 (s, 2H), 3.33 (t, 2H), 3.48 (t, 2H), 4.00 (s, 3H), 4.22 (t, 2H), 7.40 (s, 1H), 7.41 (s, 1H), 8.87 (s, 1H); Mass Spectrum: M+H+ 365/367.

Workup

  1. stirringstirring for a further 1 hr
  2. customThe resulting reaction solution
  3. customwas purified by column chromatography on silica using
  4. temperatureincreasing concentrations of methanol in dichloromethane as eluent

Sources & evidence

ORD record
ord-87f2eac24a9642afa6aba322e62d3679
Source dataset
uspto-grants-2009_03
Patent number
US07504408B2

Reaction notes

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