Tetrahydrofuran → HCID 68880358, compound

HRID 1785184Notes

Reaction equation

HRID 1785184 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][CH2:28][CH2:29][O:30][CH3:31])[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:51][CH2:52][CH2:53][CH2:54][N:55]3[CH2:60][CH2:59][O:58][CH2:57][CH2:56]3)=[CH:41][C:42]=2[O:44][CH:45]2[CH2:50][CH2:49][O:48][CH2:47][CH2:46]2)[N:37]=[CH:36][N:35]=1>CN(C=O)C>[Cl:16][C:17]1[CH:25]=[C:24]([C:26]#[C:27][CH2:28][CH2:29][O:30][CH3:31])[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:51][CH2:52][CH2:53][CH2:54][N:55]3[CH2:56][CH2:57][O:58][CH2:59][CH2:60]3)=[CH:41][C:42]=2[O:44][CH:45]2[CH2:46][CH2:47][O:48][CH2:49][CH2:50]2)[N:37]=[CH:36][N:35]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 2724254Sodium bis(trimethylsilyl)amideHCID 68881321HCID 68881321, compoundHCID 866015674-chloro-7-(3-morpholin-4-ylpropoxy)-5-(tetrahydro-2H-pyran-4-yloxy)quinazoline

Product 1

HCID 68880358HCID 68880358, compoundYield 63.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
-10 °C

Procedure

A solution of sodium bis(trimethylsilyl)amide (1.10 ml) in tetrahydrofuran (1.0M, 1.10 mmol) was added to a suspension of 5-chloro-7-(4-methoxybut-1-yn-1-yl)-1,3-benzodioxol-4-yl-amine (0.139 g) and 4-chloro-7-(3-morpholin-4-ylpropoxy)-5-(tetrahydro-2H-pyran-4-yloxy)quinazoline (0.223 g) in DMF (5 ml) that had been cooled to −10° C. and the mixture was stirred for 90 minutes then the reaction was allowed to warm to room temperature and stirred for a further 2 hours. The reaction mixture was quenched into water and saturated ammonium chloride solution was added. This was then extracted into dichloromethane and the organic portion was washed with brine, dried over magnesium sulfate and evaporated. The residue was purified by column chromatography on silica using increasingly polar mixtures of dichloromethane and methanol as eluent. The product material gathered after chromatography as a foam was triturated with diethyl ether and air-dried giving an off-white solid. There was thus obtained the title compound (0.216 g) as a grey solid;

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for a further 2 hours
  3. customThe reaction mixture was quenched into water and saturated ammonium chloride solution
  4. additionwas added
  5. extractionThis was then extracted into dichloromethane
  6. washthe organic portion was washed with brine
  7. dry with materialdried over magnesium sulfate
  8. customevaporated
  9. customThe residue was purified by column chromatography on silica using
  10. temperatureincreasingly polar mixtures of dichloromethane and methanol as eluent
  11. customwas triturated with diethyl ether
  12. customair-dried
  13. customgiving an off-white solid

Sources & evidence

ORD record
ord-a5cbadec675348bd8b6d4b2d2eed6ed8
Source dataset
uspto-grants-2009_03
Patent number
US07504408B2

Reaction notes

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