Tetrahydrofuran → N-(5-chloro-7-ethynyl-1,3-benzodioxol-4-yl)-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-amine

HRID 1785162Notes

Reaction equation

HRID 1785162 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].O1CCCC1.[Cl:16][C:17]1[CH:25]=[C:24]([C:26]#[C:27][Si](C)(C)C)[C:20]2[O:21][CH2:22][O:23][C:19]=2[C:18]=1[NH2:32].Cl[C:34]1[C:43]2[C:38](=[CH:39][C:40]([O:46][CH2:47][CH2:48][CH2:49][N:50]3[CH2:55][CH2:54][O:53][CH2:52][CH2:51]3)=[C:41]([O:44][CH3:45])[CH:42]=2)[N:37]=[CH:36][N:35]=1>CN(C=O)C.[Cl-].[NH4+]>[Cl:16][C:17]1[CH:25]=[C:24]([C:26]#[CH:27])[C:20]2[O:21][CH2:22][O:23][C:19]=2[C:18]=1[NH:32][C:34]1[C:43]2[C:38](=[CH:39][C:40]([O:46][CH2:47][CH2:48][CH2:49][N:50]3[CH2:51][CH2:52][O:53][CH2:54][CH2:55]3)=[C:41]([O:44][CH3:45])[CH:42]=2)[N:37]=[CH:36][N:35]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 2724254Sodium bis(trimethylsilyl)amideHCID 118239414-Chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolineHCID 688817345-Chloro-7-[(trimethylsilyl)ethynyl]-1,3-benzodioxol-4-amine

Product 1

HCID 86601565N-(5-chloro-7-ethynyl-1,3-benzodioxol-4-yl)-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-amineYield 58.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
0 °C

Procedure

A solution of sodium bis(trimethylsilyl)amide (0.91 ml) in tetrahydrofuran (1.0M, 0.91 mmol) was added over 5 min. to a stirred mixture of {5-chloro-7-[(trimethylsilyl)ethynyl]-1,3-benzodioxol-4-yl}amine (0.122 g) and 4-chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline (0.140 g) in DMF (4 ml) cooled to 0° C. under a nitrogen atmosphere and the mixture was stirred for 1 hr at ambient temperature. The mixture was diluted with saturated aqueous ammonium chloride (40 ml) and extracted with ethyl acetate (3×20 ml). The organic extracts were washed with brine (20 ml), dried over sodium sulphate and then evaporated. The residue was purified by column chromatography on silica using increasingly polar mixtures of methanol and dichloromethane as eluent. There was thus obtained the title compound as a solid (0.120 g). NMR Spectrum: (DMSOd6) 1.95 (m, 2H), 2.37 (m, 4H), 2.45 (t, 2H), 3.57 (m, 4H), 3.92 (s, 3H), 4.17 (t, 2H), 4.50 (s, 1H), 6.15 (s, 2H), 7.15 (s, 1H), 7.17 (s, 1H), 7.82 (s, 1H), 8.32 (s, 1H), 9.50 (s, 1H); Mass Spectrum: M+H+ 497 and 499.

Workup

  1. extractionextracted with ethyl acetate (3×20 ml)
  2. washThe organic extracts were washed with brine (20 ml)
  3. dry with materialdried over sodium sulphate
  4. customevaporated
  5. customThe residue was purified by column chromatography on silica using
  6. temperatureincreasingly polar mixtures of methanol and dichloromethane as eluent

Sources & evidence

ORD record
ord-a63e5ccd836d4687a6eccc8a3bc7a955
Source dataset
uspto-grants-2009_03
Patent number
US07504408B2

Reaction notes

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