Potassium Iodide → 4-(5-Chloro-2,3-methylenedioxypyrid-4-ylamino)-6-methoxy-7-[3-(4-prop-2-ynylpiperazin-1-yl)propoxy]quinazoline

HRID 2374423

Reaction equation

HRID 2374423 reaction equation
[Cl:1][C:2]1[C:3]([NH:11][C:12]2[C:21]3[C:16](=[CH:17][C:18]([O:24][CH2:25][CH2:26][CH2:27]Cl)=[C:19]([O:22][CH3:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)=[C:4]2[O:10][CH2:9][O:8][C:5]2=[N:6][CH:7]=1.[CH2:29]([N:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1)[C:30]#[CH:31].[I-].[K+]>CC(N(C)C)=O>[Cl:1][C:2]1[C:3]([NH:11][C:12]2[C:21]3[C:16](=[CH:17][C:18]([O:24][CH2:25][CH2:26][CH2:27][N:35]4[CH2:36][CH2:37][N:32]([CH2:29][C:30]#[CH:31])[CH2:33][CH2:34]4)=[C:19]([O:22][CH3:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)=[C:4]2[O:10][CH2:9][O:8][C:5]2=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 4875Potassium IodideHCID 146273691-(2-Propynyl)piperazineHCID 685485214-(5-Chloro-2,3-methylenedioxypyrid-4-ylamino)-7-(3-chloropropoxy)-6-methoxyquinazoline

Product 1

HCID 98492404-(5-Chloro-2,3-methylenedioxypyrid-4-ylamino)-6-methoxy-7-[3-(4-prop-2-ynylpiperazin-1-yl)propoxy]quinazolineYield 68.3%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 4-(5-chloro-2,3-methylenedioxypyrid-4-ylamino)-7-(3-chloropropoxy)-6-methoxyquinazoline (0.08 g), 1-prop-2-ynylpiperazine (0.047 g), potassium iodide (0.01 g) and DMA (2 ml) was stirred and heated to 80° C. for 3.5 hours. The solvent was evaporated and the residue was partitioned between methylene chloride and a saturated aqueous ammonium chloride solution. The organic phase was dried over magnesium sulphate and evaporated. The residue was purified by column chromatography on silica using a 19:1 mixture of methylene chloride and methanol and then a 9:1 mixture of methylene chloride and a saturated methanolic ammonia solution as eluent. The resulting gum was triturated under diethyl ether. There was thus obtained the title compound as a solid (0.066 g); NMR Spectrum: (DMSOd6 and CF3CO2D) 2.3 (m, 2H), 3.2-3.6 (br m, 10H), 3.75 (s, 1H), 3.95 (br s, 2H), 4.0 (s, 3H), 4.35 (m, 2H), 6.3 (s, 2H), 7.4 (s, 1H), 7.9 (s, 1H), 8.15 (s, 1H), 8.95 (s, 1H); Mass Spectrum: M+H+ 511 and 513.

Workup

  1. customThe solvent was evaporated
  2. customthe residue was partitioned between methylene chloride
  3. dry with materialThe organic phase was dried over magnesium sulphate
  4. customevaporated
  5. customThe residue was purified by column chromatography on silica using
  6. additiona 19:1 mixture of methylene chloride and methanol
  7. additiona 9:1 mixture of methylene chloride
  8. customThe resulting gum was triturated under diethyl ether

Sources & evidence

ORD record
ord-fadac8a8289843d596ed7cac4873929f
Source dataset
uspto-grants-2008_12
Patent number
US07462623B2

Linked notes

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