Sodium Iodide → HCID 10077238, compound

HRID 1785189Notes

Reaction equation

HRID 1785189 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:31][CH2:32][CH2:33][CH2:34]Cl)=[CH:24][C:25]=2[O:27][CH:28]([CH3:30])[CH3:29])[N:20]=[CH:19][N:18]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:55][N:56]1[CH2:61][CH2:60][NH:59][CH2:58][C:57]1=[O:62].[I-].[Na+]>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:31][CH2:32][CH2:33][CH2:34][N:59]3[CH2:60][CH2:61][N:56]([CH3:55])[C:57](=[O:62])[CH2:58]3)=[CH:24][C:25]=2[O:27][CH:28]([CH3:29])[CH3:30])[N:20]=[CH:19][N:18]=1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 11776TriphenylphosphineHCID 43990421-Methylpiperazin-2-oneHCID 68882095HCID 68882095, compound

Product 1

HCID 10077238HCID 10077238, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 80192-MethoxyethanolSolvent

Conditions

Temperature
110 °C

Procedure

A mixture N-[5-chloro-7-(3-methoxyprop-1-yn-1-yl)-1,3-benzodioxol-4-yl]-7-(3-chloropropoxy)-5-isopropoxyquinazolin-4-amine (0.320 g, as a 1:1.3 wt.:wt. mixture with triphenylphosphine) and 1-methylpiperazin-2-one (0.280 g) was dissolved in 2-methoxyethanol (7 ml), then sodium iodide (0.040 g) was added and the reaction mixture was then heated at 110° C. with stirring for 24 hours. The reaction mixture was then cooled to room temperature, diluted with dichloromethane (70 ml) and washed with water:brine (1:1) then water then brine and dried over magnesium sulfate before filtration and evaporation of solvents under reduced pressure. The residues so resulting were then purified by column chromatography on silica using increasingly polar mixtures of methanol in dichloromethane as eluent. There was thus obtained 4-(3-{4-[5-chloro-7-(3-methoxy-prop-1-ynyl)-benzo[1,3]dioxol-4-ylamino]-5-isopropoxy-quinazolin-7-yloxy}-propoxy)-1-methyl-piperazin-2-one (0.086 g) as a white foam; NMR Spectrum: (CDCl3) 1.53 (d, 6H), 2.02 (quin, 2H), 2.61 (t, 2H), 2.72 (t, 2H), 2.96 (s, 3H), 3.18 (s, 2H), 3.33 (t, 2H), 3.45 (s, 3H), 4.15 (t, 2H), 4.35 (s, 2H), 4.83 (sept, 1H), 6.10 (s, 2H), 6.49 (d, 1H), 6.82 (d, 1H), 7.05 (s, 1H), 8.51 (s, 1H), 9.41 (s, 1H); Mass Spectrum: M+H+ 596/598.

Workup

  1. temperatureThe reaction mixture was then cooled to room temperature
  2. washwashed with water:brine (1:1)
  3. dry with materialwater then brine and dried over magnesium sulfate before filtration and evaporation of solvents under reduced pressure
  4. customThe residues so resulting
  5. customwere then purified by column chromatography on silica using
  6. temperatureincreasingly polar mixtures of methanol in dichloromethane as eluent

Sources & evidence

ORD record
ord-8de7396af30549bcb1281b6304d58282
Source dataset
uspto-grants-2009_03
Patent number
US07504408B2

Reaction notes

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