Tetrahydrofuran → N-[5-chloro-7-(3-methoxybut-1-yn-1-yl)-1,3-benzodioxol-4-yl]-6,7-dimethoxyquinazolin-4-amine

HRID 1785173Notes

Reaction equation

HRID 1785173 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][CH:28]([O:30][CH3:31])[CH3:29])[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][CH3:47])=[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]#[C:27][CH:28]([O:30][CH3:31])[CH3:29])[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][CH3:47])=[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 27693644-Chloro-6,7-dimethoxyquinazolineHCID 688801585-Chloro-7-(3-methoxybut-1-yn-1-yl)-1,3-benzodioxol-4-amine

Product 1

HCID 68880608N-[5-chloro-7-(3-methoxybut-1-yn-1-yl)-1,3-benzodioxol-4-yl]-6,7-dimethoxyquinazolin-4-amine

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
0 °C

Procedure

A solution of sodium bis(trimethylsilyl)amide (1.7 ml) in tetrahydrofuran (1.0M, 1.7 mmol) was added over 5 minutes to a stirred mixture of 5-chloro-7-(3-methoxybut-1-yn-1-yl)-1,3-benzodioxol-4-amine (0.211 g) and 4-chloro-6,7-dimethoxyquinazoline (0.170 g) in DMF (7.0 ml) cooled to 0° C. under a nitrogen atmosphere; the resultant mixture was stirred for 1 hr at ambient temperature. The reaction mixture was diluted with saturated aqueous ammonium chloride (70 ml) and extracted with ethyl acetate (3×30 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 ethyl acetate and isohexane as eluent. There was thus obtained the title compound as a racemate and in a solid form (0.200 g). NMR Spectrum: (DMSOd6) 1.41 (d, 3H), 3.35 (s, 3H), 3.92 (s, 6H), 4.39 (q, 1H), 6.15 (s, 2H), 7.13 (s, 1H), 7.18 (s, 1H), 7.82 (s, 1H), 8.32 (s, 1H), 9.50 (s, 1H);

Workup

  1. extractionextracted with ethyl acetate (3×30 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 ethyl acetate and isohexane as eluent

Sources & evidence

ORD record
ord-ff904252872842a3a22a3f89f7307143
Source dataset
uspto-grants-2009_03
Patent number
US07504408B2

Reaction notes

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