Dimethylformamide → 4-(7-Benzyloxyoxindol-3-yl)-6-methoxy-7-(3-morpholinopropoxy)quinazoline

HRID 1386281Notes

Reaction equation

HRID 1386281 reaction equation
[H-].[Na+].[CH2:3]([O:10][C:11]1[CH:12]=[CH:13][CH:14]=[C:15]2[C:19]=1[NH:18][C:17](=[O:20])[CH2:16]2)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl[C:22]1[C:31]2[C:26](=[CH:27][C:28]([O:34][CH2:35][CH2:36][CH2:37][N:38]3[CH2:43][CH2:42][O:41][CH2:40][CH2:39]3)=[C:29]([O:32][CH3:33])[CH:30]=2)[N:25]=[CH:24][N:23]=1.CN(C=O)C>C1COCC1>[CH2:3]([O:10][C:11]1[CH:12]=[CH:13][CH:14]=[C:15]2[C:19]=1[NH:18][C:17](=[O:20])[CH:16]2[C:22]1[C:31]2[C:26](=[CH:27][C:28]([O:34][CH2:35][CH2:36][CH2:37][N:38]3[CH2:39][CH2:40][O:41][CH2:42][CH2:43]3)=[C:29]([O:32][CH3:33])[CH:30]=2)[N:25]=[CH:24][N:23]=1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 118239414-Chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolineHCID 217172307-Benzyloxyoxindole

Product 1

HCID 217171994-(7-Benzyloxyoxindol-3-yl)-6-methoxy-7-(3-morpholinopropoxy)quinazolineYield 58.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Sodium hydride (36 mg, 1.5 mmol) was added in portions to a solution of 7-benzyloxyoxindole (360 mg, 1.5 mmol) in THF (8 ml), the mixture was stirred for 30 minutes at ambient temperature and a solution of 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (204 mg, 0.6 mmol), (prepared as described for the starting material in Example 5), in THF (4 ml) and DMF (1.5 ml) was added. The mixture was stirred for 30 minutes at ambient temperature followed by 1.5 hours at 65° C. The THF was removed by evaporation, the mixture was partitioned between ethyl acetate and water and the aqueous layer was adjusted to pH8 with 2M hydrochloric acid. The precipitated product was collected by filtration, washed with water, ethyl acetate, and ether, and dried under vacuum to give 4-(7-benzyloxyoxindol-3-yl)-6-methoxy-7-(3-morpholinopropoxy)quinazoline (190 mg, 58%).

Workup

  1. stirringThe mixture was stirred for 30 minutes at ambient temperature
  2. waitfollowed by 1.5 hours at 65° C
  3. customThe THF was removed by evaporation
  4. customthe mixture was partitioned between ethyl acetate and water
  5. filtrationThe precipitated product was collected by filtration
  6. washwashed with water, ethyl acetate, and ether
  7. customdried under vacuum

Sources & evidence

ORD record
ord-bf614ded2efb4a0f9632bbb96a78f103
Source dataset
uspto-grants-2001_07
Patent number
US06265411B1

Reaction notes

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