Tetrahydrofuran → HCID 68884085, compound

HRID 1785168Notes

Reaction equation

HRID 1785168 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].O1CCCC1.[NH2:16][C:17]1[C:22]2[O:23][CH2:24][O:25][C:21]=2[C:20]([C:26]#[C:27][C:28]([CH3:31])([OH:30])[CH3:29])=[CH:19][C:18]=1[Cl: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:32][C:18]1[CH:19]=[C:20]([C:26]#[C:27][C:28]([CH3:29])([OH:30])[CH3:31])[C:21]2[O:25][CH2:24][O:23][C:22]=2[C:17]=1[NH:16][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 68881408HCID 68881408, compound

Product 1

HCID 68884085HCID 68884085, compoundYield 50.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
0 °C

Procedure

A solution of sodium bis(trimethylsilyl)amide (1.5 ml) in tetrahydrofuran (1.0M, 1.5 mmol) was added over 5 min. to a stirred mixture of 4-(7-amino-6-chloro-1,3-benzodioxol-4yl)-2-methylbut-3-yn-2-ol (0.186 g) and 4-chloro-6,7-dimethoxyquinazoline (0.150 g) in DMF (6.5 ml) cooled to 0° C. under a nitrogen atmosphere. The 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 solid (0.150 g). NMR Spectrum: (DMSOd6) 1.47 (s, 6H), 3.90 (s, 3H), 3.91 (s, 3H), 5.50 (s, 1H), 6.13 (s, 2H), 7.04 (s, 1H), 7.17 (s, 1H), 7.80 (s, 1H), 8.31 (s, 1H), 9.48 (s, 1H); Mass Spectrum: M+H+ 442 and 444.

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-7f3d20b3e59140b39dfe448353bd2730
Source dataset
uspto-grants-2009_03
Patent number
US07504408B2

Reaction notes

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