Sodium bis(trimethylsilyl)amide → N-[5-chloro-7-(3-ethoxyprop-1-yn-1-yl)-1,3-benzodioxol-4-yl]-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-amine

HRID 1785103Notes

Reaction equation

HRID 1785103 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][O:21][CH2:20][CH2:19]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[Cl:24][C:25]1[CH:33]=[C:32]([C:34]#[C:35][CH2:36][O:37][CH2:38][CH3:39])[C:28]2[O:29][CH2:30][O:31][C:27]=2[C:26]=1[NH2:40].C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>CN(C=O)C>[Cl:24][C:25]1[CH:33]=[C:32]([C:34]#[C:35][CH2:36][O:37][CH2:38][CH3:39])[C:28]2[O:29][CH2:30][O:31][C:27]=2[C:26]=1[NH:40][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][O:21][CH2:20][CH2:19]3)=[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 118239414-Chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolineHCID 688815535-Chloro-7-(3-ethoxyprop-1-yn-1-yl)-1,3-benzodioxol-4-amine

Product 1

HCID 10392916N-[5-chloro-7-(3-ethoxyprop-1-yn-1-yl)-1,3-benzodioxol-4-yl]-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-amineYield 79.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

This was prepared using the method described in example 4 using 4-chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline (200 mg, 0.59 mmol), 5-chloro-7-(3-ethoxyprop-1-yn-1-yl)-1,3-benzodioxol-4-amine (165 mg, 0.65 mmol) and a solution of sodium bis(trimethylsilyl)amide (1.0M in THF, 1.24 ml) in DMF (3 ml). The crude product was purified by column chromatography on silica using increasing concentrations of methanol in dichloromethane as eluent. There was thus obtained the title compound (261 mg, 79%) as a pale yellow solid; NMR Spectrum:(DMSOd6) 1.17 (t, 3H), 1.96 (quintet, 2H), 2.39 (m, 4H), 2.46 (t, 2H), 3.60 (m, 6H), 3.93 (s, 3H), 4.19 (t, 2H), 4.40 (s, 2H), 6.17 (s, 2H), 7.17 (s, 1H), 7.20 (s, 1H), 7.82 (s, 1H), 8.33 (s, 1H), 9.54 (s, 1H); Mass Spectrum: M+H+ 555/557.

Workup

  1. customThis was prepared
  2. customThe crude product was purified by column chromatography on silica using
  3. temperatureincreasing concentrations of methanol in dichloromethane as eluent

Sources & evidence

ORD record
ord-98a753213cf941e28486fe2eb805ad86
Source dataset
uspto-grants-2009_03
Patent number
US07504408B2

Reaction notes

Loading…