Tetrahydrofuran → 7-(2-Carboxyvinyl)-6-methoxy-4-(2-methylindol-5-yloxy)quinazoline

HRID 1791608Notes

Reaction equation

HRID 1791608 reaction equation
[Na].C[Si](N[Si](C)(C)C)(C)C.C1COCC1.[C:16]([CH:19]=[CH:20][C:21]1[CH:30]=[C:29]2[C:24]([C:25]([O:31][C:32]3[CH:37]=[CH:36][C:35](Cl)=[CH:34][C:33]=3F)=[N:26][CH:27]=[N:28]2)=[CH:23][C:22]=1[O:40][CH3:41])([OH:18])=[O:17].OC1C=C2C(=CC=1)[NH:48][C:47]([CH3:52])=[CH:46]2>CS(C)=O>[C:16]([CH:19]=[CH:20][C:21]1[CH:30]=[C:29]2[C:24]([C:25]([O:31][C:32]3[CH:37]=[C:36]4[C:35](=[CH:34][CH:33]=3)[NH:48][C:47]([CH3:52])=[CH:46]4)=[N:26][CH:27]=[N:28]2)=[CH:23][C:22]=1[O:40][CH3:41])([OH:18])=[O:17]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 833362-methyl-1H-indol-5-olHCID 45051731Sodium hexamethyidisilazaneHCID 541944267-(2-Carboxyvinyl)-4-(4-chloro-2-fluorophenoxy)-6-methoxyquinazoline

Product 1

HCID 544334557-(2-Carboxyvinyl)-6-methoxy-4-(2-methylindol-5-yloxy)quinazolineYield 71.4%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

1M Sodium HMDS in THF (0.84 ml, 8.4 mmol) was added to a suspension of 7-(2-carboxyvinyl)-4-(4-chloro-2-fluorophenoxy)-6-methoxyquinazoline (105 mg, 0.28 mmol) and 5-hydroxy-2methylindole (82 mg, 0.56 mmol), (prepared as described for the starting material in Example 48), in DMSO (1.5 ml). After stirring for 2 hours at ambient temperature, the mixture was partitioned between ethyl acetate and water. The aqueous layer was adjusted to pH3 with 2M hydrochloric acid. The organic layer was washed with water, brine, dried (MgSO4) and evaporated. The residue was purified by column chromatography eluting with methylene chloride/methanol (95/5 followed by 90/10 and 70/30) to give 7-(2-carboxyvinyl)-6-methoxy-4-(2-methylindol-5-yloxy)quinazoline (75 mg, 71%).

Workup

  1. custom(prepared
  2. customthe mixture was partitioned between ethyl acetate and water
  3. washThe organic layer was washed with water, brine
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customThe residue was purified by column chromatography
  7. washeluting with methylene chloride/methanol (95/5 followed by 90/10 and 70/30)

Sources & evidence

ORD record
ord-c762e8e8205e40a5b0790bfd72e40a24
Source dataset
uspto-grants-2006_07
Patent number
US07074800B1

Reaction notes

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