Sodium Iodide → 3-(4-acetylpiperazin-1-yl)propoxyl-N-[5-chloro-7-(3-methoxyprop-1-yn-1-yl)-1,3-benzodioxol-4-yl]-6-methoxyquinazolin-4-amine

HRID 1785178Notes

Reaction equation

HRID 1785178 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](OCCCCl)=[C:24]([O:27][CH3:28])[CH:25]=2)[N:20]=[CH:19][N:18]=1.[C:34]([N:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1)(=[O:36])[CH3:35].[I-].[Na+]>COCCO.ClCCl>[C:34]([N:37]1[CH2:42][CH2:41][N:40]([CH2:3][CH2:4][CH2:5][O:6][C:19]2[N:18]=[C:17]([NH:16][C:3]3[C:4]4[O:8][CH2:7][O:6][C:5]=4[C:9]([C:11]#[C:12][CH2:13][O:14][CH3:15])=[CH:10][C:2]=3[Cl:1])[C:26]3[C:21](=[CH:22][CH:23]=[C:24]([O:27][CH3:28])[CH:25]=3)[N:20]=2)[CH2:39][CH2:38]1)(=[O:36])[CH3:35]

Participants

6

Reactant 3

HCID 5238Sodium IodideHCID 837951-AcetylpiperazineHCID 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 866015663-(4-acetylpiperazin-1-yl)propoxyl-N-[5-chloro-7-(3-methoxyprop-1-yn-1-yl)-1,3-benzodioxol-4-yl]-6-methoxyquinazolin-4-amineYield 145%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 80192-MethoxyethanolSolvent

Conditions

Temperature
105 °C

Procedure

N-[5-chloro-7-(3-methoxyprop-1-yn-1-yl)-1,3-benzodioxol-4-yl]-7-(3-chloropropoxy)-6-methoxyquinazolin-4-amine (0.158 g) was dissolved in 2-methoxyethanol (5 ml) and then N-acetylpiperazine (0.600 g) was added and the mixture heated to 105° C. A small amount of sodium iodide was added to the reaction mixture, and heating continued for a total of 2½ hours. The reaction mixture was cooled to room temperature and then diluted with dichloromethane. The mixture was washed with a water/brine (5/1) mixture followed by brine and then dried over magnesium sulfate and 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 (0.136 g) as a pale yellow foam. NMR Spectrum: (CDCl3) 2.10 (quin, 2H), 2.43 (m, 2H), 2.47 (m, 2H), 2.57 (t, 2H), 3.46 (s, 3H), 3.47 (m, 2H), 3.49 (s, 3H), 3.62 (t, 3H), 3.98 (s, 3H), 4.25 (t, 2H), 4.35 (s, 2H), 6.08 (s, 2H), 7.06 (s, 1H), 7.20 (s, 1H), 7.28 (s, 2H), 8.62 (s, 1H); Mass Spectrum: M+H+ 582/584.

Workup

  1. temperatureheating
  2. customcontinued for a total of 2½ hours
  3. temperatureThe reaction mixture was cooled to room temperature
  4. washThe mixture was washed with a water/brine (5/1) mixture
  5. dry with materialdried over magnesium sulfate
  6. customevaporated
  7. customThe residue was purified by column chromatography on silica using
  8. temperatureincreasingly polar mixtures of dichloromethane and methanol as eluent

Sources & evidence

ORD record
ord-2467d81877434cfe8187954255027fdb
Source dataset
uspto-grants-2009_03
Patent number
US07504408B2

Reaction notes

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