Tetrahydrofuran → HCID 68884240, compound

HRID 1785170Notes

Reaction equation

HRID 1785170 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][CH2:28][O:29][CH2:30][C:31]([N:33]([CH3:35])[CH3:34])=[O:32])=[CH:19][C:18]=1[Cl:36].Cl[C:38]1[C:47]2[C:42](=[CH:43][C:44]([O:50][CH3:51])=[C:45]([O:48][CH3:49])[CH:46]=2)[N:41]=[CH:40][N:39]=1>CN(C=O)C.[Cl-].[NH4+]>[Cl:36][C:18]1[CH:19]=[C:20]([C:26]#[C:27][CH2:28][O:29][CH2:30][C:31]([N:33]([CH3:34])[CH3:35])=[O:32])[C:21]2[O:25][CH2:24][O:23][C:22]=2[C:17]=1[NH:16][C:38]1[C:47]2[C:42](=[CH:43][C:44]([O:50][CH3:51])=[C:45]([O:48][CH3:49])[CH:46]=2)[N:41]=[CH:40][N:39]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 2724254Sodium bis(trimethylsilyl)amideHCID 27693644-Chloro-6,7-dimethoxyquinazolineHCID 688813182-{[3-(7-amino-6-chloro-1,3-benzodioxol-4-yl)prop-2-yn-1-yl]oxy}-N,N-dimethylacetamide

Product 1

HCID 68884240HCID 68884240, compoundYield 34.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
0 °C

Procedure

A solution of sodium bis(trimethylsilyl)amide (1.3 ml) in tetrahydrofuran (1.0M, 1.3 mmol) was added over 5 minutes to a stirred mixture of 2-{[3-(7-amino-6-chloro-1,3-benzodioxol-4-yl)prop-2-yn-1-yl]oxy}-N,N-dimethylacetamide (0.200 g) and 4-chloro-6,7-dimethoxyquinazoline (0.132 g) in DMF (5.7 ml) cooled to 0° C. under a nitrogen atmosphere; the resultant mixture was stirred for 1.5 hr at ambient temperature. The reaction mixture was diluted with saturated aqueous ammonium chloride (60 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 methanol and dichloromethane as eluent. There was thus obtained the title compound as a solid (0.102 g). NMR Spectrum: (DMSOd6) 2.82 (s, 3H), 2.92 (s, 3H), 3.92 (s, 6H), 4.26 (s, 2H), 4.51 (s, 2H), 6.15 (s, 2H), 7.16 (s, 1H), 7.18 (s, 1H), 7.82 (s, 1H), 8.32 (s, 1H), 9.52 (s, 1H); Mass Spectrum: M+H+ 499 and 501.

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 methanol and dichloromethane as eluent

Sources & evidence

ORD record
ord-d807c194d5f2450b9a0e3beb2c146ef9
Source dataset
uspto-grants-2009_03
Patent number
US07504408B2

Reaction notes

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