Tetrahydrofuran → HCID 68881443, compound

HRID 1785169Notes

Reaction equation

HRID 1785169 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]([NH:33][CH3:34])=[O:32])=[CH:19][C:18]=1[Cl:35].Cl[C:37]1[C:46]2[C:41](=[CH:42][C:43]([O:49][CH3:50])=[C:44]([O:47][CH3:48])[CH:45]=2)[N:40]=[CH:39][N:38]=1>CN(C=O)C.[Cl-].[NH4+]>[Cl:35][C:18]1[CH:19]=[C:20]([C:26]#[C:27][CH2:28][O:29][CH2:30][C:31]([NH:33][CH3:34])=[O:32])[C:21]2[O:25][CH2:24][O:23][C:22]=2[C:17]=1[NH:16][C:37]1[C:46]2[C:41](=[CH:42][C:43]([O:49][CH3:50])=[C:44]([O:47][CH3:48])[CH:45]=2)[N:40]=[CH:39][N:38]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 2724254Sodium bis(trimethylsilyl)amideHCID 27693644-Chloro-6,7-dimethoxyquinazolineHCID 68882631HCID 68882631, compound

Product 1

HCID 68881443HCID 68881443, compoundYield 39.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
0 °C

Procedure

A solution of sodium bis(trimethylsilyl)amide (1.23 ml) in tetrahydrofuran (1.0M, 1.23 mmol) was added over 5 min. to a stirred mixture of 2-{[3-(7-amino-6-chloro-1,3-benzodioxol-4-yl)prop-2-yn-1-yl]oxy}-N-methylacetamide (0.182 g) and 4chloro-6,7-dimethoxyquinazoline (0.125 g) in DMF (6.0 ml) cooled to 0° C. under a nitrogen atmosphere; the mixture was stirred for 1.25 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 (30 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 (0.106 g). NMR Spectrum: (DMSOd6) 2.62 (d, 3H), 3.91 (s, 6H), 3.98 (s, 2H), 4.50 (s, 2H), 6.15 (s, 2H), 7.15 (s, 1H), 7.17 (s, 1H), 7.76 (s, 1H), 7.80 (s, 1H), 8.31 (s, 1H), 9.52 (s, 1H); Mass Spectrum: M+H+ 485 and 487.

Workup

  1. extractionextracted with ethyl acetate (3×30 ml)
  2. washThe organic extracts were washed with brine (30 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-08d35b9850c3446c9808c062d9860307
Source dataset
uspto-grants-2009_03
Patent number
US07504408B2

Reaction notes

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