Tetrahydrofuran → 6-methoxy-N-[5-chloro-7-(3-methoxyprop-1-ynyl)-1,3-benzodioxol-4-yl]-7-[3-(4-methylpiperazin-1-yl)propoxy]quinazolin-4-amine

HRID 1785091Notes

Reaction equation

HRID 1785091 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].O1CCCC1.Cl[C:17]1[C:26]2[C:21](=[CH:22][C:23]([O:29][CH2:30][CH2:31][CH2:32][N:33]3[CH2:38][CH2:37][N:36]([CH3:39])[CH2:35][CH2:34]3)=[C:24]([O:27][CH3:28])[CH:25]=2)[N:20]=[CH:19][N:18]=1.[Cl:40][C:41]1[CH:49]=[C:48]([C:50]#[C:51][CH2:52][O:53][CH3:54])[C:44]2[O:45][CH2:46][O:47][C:43]=2[C:42]=1[NH2:55]>CN(C=O)C.[Cl-].[NH4+]>[CH3:28][O:27][C:24]1[CH:25]=[C:26]2[C:21](=[CH:22][C:23]=1[O:29][CH2:30][CH2:31][CH2:32][N:33]1[CH2:38][CH2:37][N:36]([CH3:39])[CH2:35][CH2:34]1)[N:20]=[CH:19][N:18]=[C:17]2[NH:55][C:42]1[C:43]2[O:47][CH2:46][O:45][C:44]=2[C:48]([C:50]#[C:51][CH2:52][O:53][CH3:54])=[CH:49][C:41]=1[Cl:40]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 2724254Sodium bis(trimethylsilyl)amideHCID 112450614-Chloro-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinazolineHCID 210827165-Chloro-7-(3-methoxyprop-1-ynyl)-1,3-benzodioxol-4-amine

Product 1

HCID 688815766-methoxy-N-[5-chloro-7-(3-methoxyprop-1-ynyl)-1,3-benzodioxol-4-yl]-7-[3-(4-methylpiperazin-1-yl)propoxy]quinazolin-4-amineYield 65.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
0 °C

Procedure

A solution of sodium bis(trimethylsilyl)amide (1.33 ml) in tetrahydrofuran (1.0 Mol/L, 1.33 mmol) was added to a solution of 4-chloro-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinazoline (0.212 g) and 5-chloro-7-(3-methoxyprop-1-ynyl)-1,3-benzodioxol-4-amine (0.16 g) in DMF (3 ml) cooled to 0° C. under a nitrogen atmosphere. The reaction mixture was stirred for 1.5 hours. The reaction mixture was diluted with a saturated solution of ammonium chloride and extracted twice with ethyl acetate. The organic phases were combined and dried over magnesium sulfate and evaporated in vacuo. The residue was purified by column chromatography on silica using increasingly polar mixtures of dichloromethane and methanol as the eluent to give the title compound as a light brown solid (0.22 g). NMR Spectrum: 1.93 (m, 2H), 2.12 (s, 3H), 2.22-2.50 (m, 10H), 3.36 (s, 3H), 3.93 (s, 3H), 4.17 (t, 2H), 4.35 (s, 2H), 6.14 (s, 2H), 7.14 (s, 1H), 7.15 (s, 1H), 7.80 (s, 1H), 8.29 (s, 1H), 9.49 (s, 1H); Mass Spectrum: M+H+ 554, M+H− 552.

Workup

  1. extractionextracted twice with ethyl acetate
  2. dry with materialdried over magnesium sulfate
  3. customevaporated in vacuo
  4. customThe residue was purified by column chromatography on silica using
  5. temperatureincreasingly polar mixtures of dichloromethane and methanol as the eluent

Sources & evidence

ORD record
ord-4708001b55df41498dd9dd946d2cabec
Source dataset
uspto-grants-2009_03
Patent number
US07504408B2

Reaction notes

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