Sodium bis(trimethylsilyl)amide → 1-{3-[(4-{[5-Chloro-7-(pyridin-2-ylethynyl)-1,3-benzodioxol-4-yl]amino}-6-methoxyquinazolin-7-yl)oxy]propyl}-4-methylpiperazin-2-one

HRID 1785149Notes

Reaction equation

HRID 1785149 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][C:19]3=[O:25])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[Cl:26][C:27]1[CH:35]=[C:34]([C:36]#[C:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][N:39]=2)[C:30]2[O:31][CH2:32][O:33][C:29]=2[C:28]=1[NH2:44].C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>CN(C=O)C>[Cl:26][C:27]1[CH:35]=[C:34]([C:36]#[C:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][N:39]=2)[C:30]2[O:31][CH2:32][O:33][C:29]=2[C:28]=1[NH:44][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][C:19]3=[O:25])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 68881051HCID 68881051, compoundHCID 866015631-{3-[(4-Chloro-6-methoxyquinazolin-7-yl)oxy]propyl}-4-methylpiperazin-2-one

Product 1

HCID 100314931-{3-[(4-{[5-Chloro-7-(pyridin-2-ylethynyl)-1,3-benzodioxol-4-yl]amino}-6-methoxyquinazolin-7-yl)oxy]propyl}-4-methylpiperazin-2-oneYield 81.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

This was prepared by the method described in example 4 but using 1-{3-[(4-chloro-6-methoxyquinazolin-7-yl)oxy]propyl}-4-methylpiperazin-2-one (137 mg, 0.37 mmol), 5-chloro-7-(pyridin-2-ylethynyl)-1,3-benzodioxol-4-amine (113 mg, 0.41 mmol) and sodium bis(trimethylsilyl)amide (1.0M in THF, 0.8 ml) in DMF (2 ml). The crude product was purified by column chromatography on silica using 10% methanol in dichloromethane as eluent. There was thus obtained the title compound (181 mg, 80%) as a pale yellow solid; NMR Spectrum:(DMSOd6) 2.21 (quintet, 2H), 2.31 (s, 3H), 2.63 (t, 2H), 3.09 (s, 2H), 3.38 (t, 2H), 3.61 (t, 2H), 3.97 (s, 3H), 4.20 (t, 2H), 6.08 (s, 2H), 7.18 (d, 2H), 7.25 (m, 3H), 7.54 (d, 1H), 7.70 (t, 1H), 8.62 (m, 2H); Mass Spectrum: M+H+ 601/603.

Workup

  1. customThis was prepared by the method
  2. customThe crude product was purified by column chromatography on silica using 10% methanol in dichloromethane as eluent

Sources & evidence

ORD record
ord-a2c30214ee1d4d6aa242cf1f80cba6b9
Source dataset
uspto-grants-2009_03
Patent number
US07504408B2

Reaction notes

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