Piperazine → N-[5-chloro-7-(3-methoxyprop-1-yn-1-yl)-1,3-benzodioxol-4-yl]-6-methoxy-7-[3-piperazin-1-ylpropoxy]-quinazolin-4-amine

HRID 1785180Notes

Reaction equation

HRID 1785180 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][CH2:35]1>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:34]3[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]3)=[C:24]([O:27][CH3:28])[CH:25]=2)[N:20]=[CH:19][N:18]=1

Participants

5

Reactant 2

HCID 4837PiperazineHCID 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 68884133N-[5-chloro-7-(3-methoxyprop-1-yn-1-yl)-1,3-benzodioxol-4-yl]-6-methoxy-7-[3-piperazin-1-ylpropoxy]-quinazolin-4-amineYield 69.3%

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 (0.165 g) was dissolved in 2-methoxyethanol (5 ml) and piperazine (0.586 g) was then added and the mixture heated to 110° C. for 45 minutes. 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 with methanolic ammonia as eluent. There was thus obtained the title compound (0.126 g) as a clear gum; NMR Spectrum: (CDCl3) 2.09 (quin, 2H), 2.46 (s(broad), 4H), 2.54 (t, 2H), 2.91 (t, 4H), 3.45 (s, 3H), 3.47 (s, 1H), 3.96 (s, 3H), 4.23 (t, 2H), 4.35 (s, 2H), 6.06 (s, 2H), 7.06 (s, 1H), 7.13 (s, 1H), 7.28 (s, 2H), 8.62 (s, 1H); Mass Spectrum: M+H+ 540/542.

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 with methanolic ammonia as eluent

Sources & evidence

ORD record
ord-37691c967c664d6ba8ae9ee5e32c18ff
Source dataset
uspto-grants-2009_03
Patent number
US07504408B2

Reaction notes

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