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

HRID 1785146Notes

Reaction equation

HRID 1785146 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][CH:37]([O:39][CH3:40])[CH3:38])[C:28]2[O:29][CH2:30][O:31][C:27]=2[C:26]=1[NH2:41].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][CH:37]([O:39][CH3:40])[CH3:38])[C:28]2[O:29][CH2:30][O:31][C:27]=2[C:26]=1[NH:41][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 688812175-Chloro-7-(4-methoxypent-1-yn-1-yl)-1,3-benzodioxol-4-amine

Product 1

HCID 68883797N-[5-Chloro-7-(4-methoxypent-1-yn-1-yl)-1,3-benzodioxol-4-yl]-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-amineYield 64.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

This was prepared by the method described in example 4 but using 4-chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline (200 mg, 0.59 mmol), 5-chloro-7-(4-methoxypent-1-yn-1-yl)-1,3-benzodioxole-4-amine (174 mg, 0.65 mmol) and 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 (216 mg, 64%) as an off-white solid; NMR Spectrum:(CDCl3) 1.33 (d, 3H), 2.12 (quintet, 2H), 2.47 (m, 4H), 2.55 (m, 3H), 2.74 (dd, 1H), 3.40 (s, 3H), 3.58 (m, 1H), 3.71 (m, 4H), 3.98 (s, 3H), 4.25 (t, 2H), 6.07 (s, 2H), 6.90 (s, 1H), 7.03 (s, 1H), 7.09 (s, 1H), 7.30 (s, 1H ), 8.62 (s, 1H); Mass Spectrum: M+H+ 569/571.

Workup

  1. customThis was prepared by the method
  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-7a2cbf012f724f2388fe0b5420a11e4c
Source dataset
uspto-grants-2009_03
Patent number
US07504408B2

Reaction notes

Loading…