Sodium bis(trimethylsilyl)amide → N-{5-chloro-7-[3-(2methoxyethoxy)prop-1-yn-1-yl]-1,3-benzodioxol-4-yl}-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-amine

HRID 1785104Notes

Reaction equation

HRID 1785104 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][CH2:39][O:40][CH3:41])[C:28]2[O:29][CH2:30][O:31][C:27]=2[C:26]=1[NH2:42].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][CH2:39][O:40][CH3:41])[C:28]2[O:29][CH2:30][O:31][C:27]=2[C:26]=1[NH:42][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 688813295-Chloro-7-[3-(2-methoxyethoxy)prop-1-yn-1-yl]-1,3-benzodioxol-4-amine

Product 1

HCID 68881035N-{5-chloro-7-[3-(2methoxyethoxy)prop-1-yn-1-yl]-1,3-benzodioxol-4-yl}-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-amineYield 77.6%

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-(2-methoxyethoxy)prop-1-yn-1-yl]-1,3-benzodioxol-4-amine (185 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 (268 mg, 77%) as a pale yellow solid; NMR Spectrum: (DMSOd6) 1.99 (quintet, 2H), 2.40 (m, 4H), 2.49 (t, 2H), 3.30 (s,3H), 3.52 (m, 2H), 3.59 (m, 4H), 3.65 (m, 2H), 3.93 (s, 3H), 4.20 (t, 2H), 4.44 (s, 2H), 6.16 (s, 2H), 7.16 (s, 1H), 7.19 (s, 1H), 7.82 (s, 1H), 8.32 (s, 1H), 9.5 (s, 1H); Mass Spectrum: M+H+ 585/587.

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-7463d5ac6fc3463687627bcc22aaefab
Source dataset
uspto-grants-2009_03
Patent number
US07504408B2

Reaction notes

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