2-(Dimethylamino)ethanol → 7-(2-(N,N-dimethylamino)ethoxy)-6-methoxy-4-(2-methylindol-5-yloxy)quinazoline

HRID 454060Notes

Reaction equation

HRID 454060 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.[OH:34][C:35]1[CH:44]=[C:43]2[C:38]([C:39]([O:45][C:46]3[CH:47]=[C:48]4[C:52](=[CH:53][CH:54]=3)[NH:51][C:50]([CH3:55])=[CH:49]4)=[N:40][CH:41]=[N:42]2)=[CH:37][C:36]=1[O:56][CH3:57].[CH3:58][N:59]([CH3:63])[CH2:60][CH2:61]O>C(Cl)Cl>[CH3:58][N:59]([CH2:60][CH2:61][O:34][C:35]1[CH:44]=[C:43]2[C:38]([C:39]([O:45][C:46]3[CH:47]=[C:48]4[C:52](=[CH:53][CH:54]=3)[NH:51][C:50]([CH3:55])=[CH:49]4)=[N:40][CH:41]=[N:42]2)=[CH:37][C:36]=1[O:56][CH3:57])[CH3:63]

Participants

6

Reactant 4

HCID 79022-(Dimethylamino)ethanolHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 1357631087-hydroxy-6-methoxy-4-(2-methyl-1H-indol-5-yloxy)quinazoline

Product 1

HCID 220306417-(2-(N,N-dimethylamino)ethoxy)-6-methoxy-4-(2-methylindol-5-yloxy)quinazolineYield 38%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

0.5M Triphenylphosphine in methylene chloride and diisopropyl azodicarboxylate (150 μl, 0.75 mmol) were added in portions to a suspension of 7-hydroxy-6-methoxy-4-(2-methylindol-5-yloxy)quinazoline (112 mg, 0.35 mmol), (prepared as described in Example 49), and N,N-dimethylethanolamine (62 mg, 0.7 mmol) in methylene chloride (2 ml). After stirring for 2 hours at ambient temperature, the reaction mixture was poured onto an Isolute® column (10 g of silica) and eluted with ethyl acetate/methylene chloride (1/1) followed by methanol/ethyl acetate/methylene chloride (10/40/50), methanol/methylene chloride (10/90), and 3M ammonia in methanol/methanol/methylene chloride (5/15/80). After removal of the volatiles by evaporation, the residue was dissolved in the minimum amount of methylene chloride (about 3 ml) and ether and petroleum ether (about 10 ml) was added. The resulting precipitate was collected by filtration and dried under vacuum to give 7-(2-(N,N-dimethylamino)ethoxy)-6-methoxy-4-(2-methylindol-5-yloxy)quinazoline (52 mg, 38%).

Workup

  1. additionthe reaction mixture was poured onto an Isolute® column (10 g of silica)
  2. washeluted with ethyl acetate/methylene chloride (1/1)
  3. customAfter removal of the volatiles
  4. customby evaporation
  5. dissolutionthe residue was dissolved in the minimum amount of methylene chloride (about 3 ml) and ether and petroleum ether (about 10 ml)
  6. additionwas added
  7. filtrationThe resulting precipitate was collected by filtration
  8. customdried under vacuum

Sources & evidence

ORD record
ord-a0273298ad3c4cbdbcfe261ecd983a8c
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

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