Piperazin-2-one → 4-{3-[(4-{[5-Chloro-7-(3-methoxyprop-1-yn-1-yl)-1,3-benzodioxol-4-yl]amino}-6-methoxyquinazolin-7-yl)oxy]propyl}piperazin-2-one

HRID 1785181Notes

Reaction equation

HRID 1785181 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH2:13][O:14][CH3:15])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:16][C:17]1[C:26]2[C:21](=[CH:22][C:23]([O:29][CH2:30][CH2:31][CH2:32]Cl)=[C:24]([O:27][CH3:28])[CH:25]=2)[N:20]=[CH:19][N:18]=1.[NH:34]1[CH2:39][CH2:38][NH:37][CH2:36][C:35]1=[O:40]>COCCO.ClCCl>[Cl:1][C:2]1[CH:10]=[C:9]([C:11]#[C:12][CH2:13][O:14][CH3:15])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:16][C:17]1[C:26]2[C:21](=[CH:22][C:23]([O:29][CH2:30][CH2:31][CH2:32][N:37]3[CH2:38][CH2:39][NH:34][C:35](=[O:40])[CH2:36]3)=[C:24]([O:27][CH3:28])[CH:25]=2)[N:20]=[CH:19][N:18]=1

Participants

5

Reactant 2

HCID 231360Piperazin-2-oneHCID 68882624N-[5-chloro-7-(3-methoxyprop-1-yn-1-yl)-1,3-benzodioxol-4-yl]-7-(3-chloropropoxy)-6-methoxyquinazolin-4-amine

Product 1

HCID 103704024-{3-[(4-{[5-Chloro-7-(3-methoxyprop-1-yn-1-yl)-1,3-benzodioxol-4-yl]amino}-6-methoxyquinazolin-7-yl)oxy]propyl}piperazin-2-oneYield 71.7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 80192-MethoxyethanolSolvent

Conditions

Temperature
110 °C

Procedure

N-[5-chloro-7-(3-methoxyprop-1-yn-1-yl)-1,3-benzodioxol-4-yl]-7-(3-chloropropoxy)-6-methoxyquinazolin-4-amine (0.200 g) was dissolved in 2-methoxyethanol (6 ml) and piperazine-2-one (0.821 g) was then added and the mixture heated to 110° C. for 3 hours. The reaction mixture was cooled to room temperature, diluted with dichloromethane, washed with water and brine, dried over magnesium sulfate and then evaporated. The residue was purified by column chromatography on silica using increasingly polar mixtures of dichloromethane and methanol as eluent. There was thus obtained the title compound (0.162 g) as a white powder, NMR Spectrum: (d6-DMSO) 2.10 (quin, 2H), 2.66 (m, 4H), 3.12 (s, 2H), 3.33 (m, 2H), 3.44 (s, 3H), 4.01 (s, 3H), 4.24 (t, 2H), 4.34 (s, 2H), 6.09 (s, 2H), 7.04 (, 1H), 7.06 (s, 1H), 7.19 (s, 1H), 7.77 (s, 1H), 8.46 (s, 1H), 9.04 (s, 1H); Mass Spectrum: M+H+ 554/556.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washwashed with water and brine
  3. dry with materialdried over magnesium sulfate
  4. customevaporated
  5. customThe residue was purified by column chromatography on silica using
  6. temperatureincreasingly polar mixtures of dichloromethane and methanol as eluent

Sources & evidence

ORD record
ord-062743da78aa415eb92d53bcf02b9377
Source dataset
uspto-grants-2009_03
Patent number
US07504408B2

Reaction notes

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