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

HRID 1785107Notes

Reaction equation

HRID 1785107 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][CH:39]2[CH2:41][CH2:40]2)[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][CH:39]2[CH2:41][CH2:40]2)[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 688819705-Chloro-7-[3-(cyclopropylmethoxy)prop-1-yn-1-yl]-1,3-benzodioxol-4-amine

Product 1

HCID 10325905N-{5chloro-7-[3-(cyclopropylmethoxy)prop-1-yn-1-yl]-1,3-benzodioxol-4-yl}-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-amineYield 72%

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-(cyclopropylmethoxy)prop-1-yn-1-yl]-1,3-benzodioxol-4-amine (182 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 (247 mg, 72%) as a pale yellow solid; NMR Spectrum:(DMSOd6) 0.23 (m, 2H), 0.51 (m, 2H), 1.04 (m, 1H), 1.96 (quintet, 2H), 2.38 (m, 4H), 2.46 (t, 2H), 3.37 (d, 2H), 3.59 (m, 4H), 3.93 (s, 3H), 4.20 (t, 2H), 4.42 (s, 2H), 6.16 (s, 2H), 7.15 (s, 1H), 7.19 (s, 1H), 7.84 (s, 1H), 8.34 (s, 1H), 9.52 (s, 1H); Mass Spectrum: M+H+ 581/583.

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-e90b30b417e14c0da8c9a12b575ea345
Source dataset
uspto-grants-2009_03
Patent number
US07504408B2

Reaction notes

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