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]morpholine-4-carboxamide

HRID 1785111Notes

Reaction equation

HRID 1785111 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]([N:40]2[CH2:45][CH2:44][O:43][CH2:42][CH2:41]2)=[O:39])=[CH:27][C:26]=1[Cl:46].C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>CN(C=O)C>[Cl:46][C:26]1[CH:27]=[C:28]([C:34]#[C:35][CH2:36][NH:37][C:38]([N:40]2[CH2:41][CH2:42][O:43][CH2:44][CH2:45]2)=[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 68881313N-[3-(7-amino-6-chloro-1,3-benzodioxol-4-yl)prop-2-yn-1-yl]morpholine-4-carboxamide

Product 1

HCID 68880399N-[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]morpholine-4-carboxamideYield 72.1%

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]morpholine-4-carboxamide (220 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 10% methanol in dichloromethane as eluent. There was thus obtained the title compound (272 mg, 72%) as a pale brown solid; NMR Spectrum:(DMSOd6) 1.96 (quintet, 2H), 2.39 (m, 4H), 2.47 (t, 2H), 2.50 (m, 4H), 3.55-3.62 (m, 8H), 3.94 (s, 3H), 4.14 (d, 2H), 4.20 (t, 2H), 6.15 (s, 2H), 7.10 (m, 2H), 7.20 (s, 1H), 7.82 (s, 1H), 8.34 (s, 1H), 9.50 (s, 1H); Mass Spectrum: M+H+ 639/641.

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-705e201ed1f54150bae5b932266b0257
Source dataset
uspto-grants-2009_03
Patent number
US07504408B2

Reaction notes

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