Tetrahydrofuran → N-[5-chloro-7-(3-methoxy-3-methylbut-1-yn-1-yl)-1,3-benzodioxol-4-yl]-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-amine

HRID 1785190Notes

Reaction equation

HRID 1785190 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].O1CCCC1.Cl[C:17]1[C:26]2[C:21](=[CH:22][C:23]([O:29][CH2:30][CH2:31][CH2:32][N:33]3[CH2:38][CH2:37][O:36][CH2:35][CH2:34]3)=[C:24]([O:27][CH3:28])[CH:25]=2)[N:20]=[CH:19][N:18]=1.[Cl:39][C:40]1[CH:48]=[C:47]([C:49]#[C:50][C:51]([O:54][CH3:55])([CH3:53])[CH3:52])[C:43]2[O:44][CH2:45][O:46][C:42]=2[C:41]=1[NH2:56]>CN(C=O)C>[Cl:39][C:40]1[CH:48]=[C:47]([C:49]#[C:50][C:51]([O:54][CH3:55])([CH3:53])[CH3:52])[C:43]2[O:44][CH2:45][O:46][C:42]=2[C:41]=1[NH:56][C:17]1[C:26]2[C:21](=[CH:22][C:23]([O:29][CH2:30][CH2:31][CH2:32][N:33]3[CH2:38][CH2:37][O:36][CH2:35][CH2:34]3)=[C:24]([O:27][CH3:28])[CH:25]=2)[N:20]=[CH:19][N:18]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 2724254Sodium bis(trimethylsilyl)amideHCID 118239414-Chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolineHCID 68882291HCID 68882291, compound

Product 1

HCID 68880552N-[5-chloro-7-(3-methoxy-3-methylbut-1-yn-1-yl)-1,3-benzodioxol-4-yl]-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-amine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
-15 °C

Procedure

A solution of sodium bis(trimethylsilyl)amide (1.12 ml) in tetrahydrofuran (1.0M, 1.12 mmol) was added to a solution 4-chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline (0.189 g) and 5-chloro-7-(3-methoxy-3-methylbut-1-yn-1-yl)-1,3-benzodioxol-4-amine (0.150 g) in DMF (6 ml) that had been cooled to −15° C. and the mixture was stirred for 3 hours then the reaction was allowed to warm to room temperature. The reaction mixture was quenched into water and saturated ammonium chloride solution was added. The resulting white precipitate was filtered under suction, washing with water, giving a pale tan paste. This was then extracted into dichloromethane, dried over magnesium sulfate and solvents evaporated under reduced pressure to give a tan foam. This was triturated with diethyl ether, giving a white solid. The resulting solid was then gathered by filtration and air-dried. There was thus the title compound (0.225 g) as an off-white solid; NMR Spectrum: (CDCl3) 1.55 (s, 6H), 2.11 (quin, 2H), 2.47 (s(broad), 4H), 2.56 (t, 2H), 3.43 (s, 3H), 3.72 (t, 4H), 4.00 (s, 3H), 4.26 (t, 2H), 6.07 (s, 2H), 6.83 (s, 1H), 7.05 (s, 1H), 7.08 (s, 1H), 7.30 (s, 1H), 8.62 (s, 1H); Mass Spectrum: M+H+ 569/571.

Workup

  1. temperatureto warm to room temperature
  2. customThe reaction mixture was quenched into water and saturated ammonium chloride solution
  3. additionwas added
  4. filtrationThe resulting white precipitate was filtered under suction
  5. washwashing with water
  6. customgiving a pale tan paste
  7. extractionThis was then extracted into dichloromethane
  8. dry with materialdried over magnesium sulfate and solvents
  9. customevaporated under reduced pressure
  10. customto give a tan foam
  11. customThis was triturated with diethyl ether
  12. customgiving a white solid
  13. filtrationThe resulting solid was then gathered by filtration
  14. customair-dried

Sources & evidence

ORD record
ord-f04c0f5afb224b739c6d8c6d0959da6f
Source dataset
uspto-grants-2009_03
Patent number
US07504408B2

Reaction notes

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