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

HRID 1785117Notes

Reaction equation

HRID 1785117 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.[NH2:24][C:25]1[C:30]2[O:31][CH2:32][O:33][C:29]=2[C:28]([C:34]#[C:35][CH2:36][NH:37][C:38]([NH:40][CH3:41])=[O:39])=[CH:27][C:26]=1[Cl:42].C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>CN(C=O)C>[Cl:42][C:26]1[CH:27]=[C:28]([C:34]#[C:35][CH2:36][NH:37][C:38]([NH:40][CH3:41])=[O:39])[C:29]2[O:33][CH2:32][O:31][C:30]=2[C:25]=1[NH:24][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 68884460N-[3-(7-amino-6-chloro-1,3-benzodioxol-4-yl)prop-2-yn-1-yl]-N'-methylurea

Product 1

HCID 68880485N-[3-(6-chloro-7-{[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-yl]amino}-1,3-benzodioxol-4-yl)prop-2-yn-1-yl]-N'-methylureaYield 61%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

This was prepared by the method described in example 4 using 4-chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline (200 mg, 0.59 mmol), N-[3-(7-amino-6-chloro-1,3-benzodioxol-4-yl)prop-2-yn-1-yl]-N′-methylurea (170 mg, 0.60 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 10% methanol in dichloromethane as eluent. There was thus obtained the title compound (209 mg, 61%) as a yellow solid; NMR Spectrum:(DMSOd6) 1.96 (quintet, 2H), 2.39 (m, 4H), 2.45 (t, 2H), 2.57 (d, 3H), 3.60 (m, 4H), 3.94 (s, 3H), 4.08 (d, 2H), 4.20 (t, 2H), 5.91 (q, 1H), 6.15 (s, 2H), 6.38 (t, 1H), 7.09 (s, 1H), 7.19 (s, 1H), 7.81 (s, 1H), 8.32 (s, 1H), 9.51 (s, 1H); Mass Spectrum: M+H+ 583/585.

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-13976471972b4cabb87c6b6d9052a3b2
Source dataset
uspto-grants-2009_03
Patent number
US07504408B2

Reaction notes

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