Sodium hydride → HCID 21717279, compound

HRID 1386327Notes

Reaction equation

HRID 1386327 reaction equation
[CH3:1][S:2]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][C:8](=[O:13])[CH2:7]2)=[O:3].[H-].[Na+].[Cl:16][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>CN(C=O)C>[ClH:16].[CH3:28][O:27][C:24]1[CH:25]=[C:26]2[C:21](=[CH:22][C:23]=1[O:29][CH2:30][CH2:31][CH2:32][N:33]1[CH2:34][CH2:35][O:36][CH2:37][CH2:38]1)[N:20]=[CH:19][N:18]=[C:17]2[CH:7]1[C:6]2[C:10](=[CH:11][CH:12]=[C:4]([S:2]([CH3:1])=[O:3])[CH:5]=2)[NH:9][C:8]1=[O:13]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 118239414-Chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolineHCID 21717177HCID 21717177, compound

Product 1

HCID 21717279HCID 21717279, compoundYield 29.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 5-methylsulphinyloxindole (303 mg, 1.55 mmol) in DMF (3.5 ml) was added to a suspension of sodium hydride (62 mg, 1.55 mmol, prewashed with hexane) in DMF (1.5 ml) and the mixture stirred for 30 minutes at ambient temperature. 4-Chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (175 mg, 0.51 mmol), (prepared as described for the starting material in Example 5), was added and the mixture was stirred for 1.5 hours at 50° C. and then partitioned between water and ether. The aqueous layer was adjusted to pH7-8 with 2M hydrochloric acid and the volatiles removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol (9/1). The semi-purified solid was dissolved in dilute hydrochloric acid (pH2) and purified by reverse phase C18 chromatography eluting with methanol/dilute hydrochloric acid (pH2) (gradient from 0/100 to 30/70). The methanol was removed by evaporation, the aqueous residue was freeze dried to give 6-methoxy-4-(5-methylsulphinyloxindol-3-yl)-7-(3-morpholinopropoxy)quinazoline hydrochloride (80 mg, 27%).

Workup

  1. additionwas added
  2. stirringthe mixture was stirred for 1.5 hours at 50° C.
  3. custompartitioned between water and ether
  4. customthe volatiles removed by evaporation
  5. customThe residue was purified by column chromatography
  6. washeluting with methylene chloride/methanol (9/1)
  7. dissolutionThe semi-purified solid was dissolved in dilute hydrochloric acid (pH2)
  8. custompurified by reverse phase C18 chromatography
  9. washeluting with methanol/dilute hydrochloric acid (pH2) (gradient from 0/100 to 30/70)
  10. customThe methanol was removed by evaporation
  11. customdried

Sources & evidence

ORD record
ord-21cf8b28c9f44f8c97d576a4c9e11d68
Source dataset
uspto-grants-2001_07
Patent number
US06265411B1

Reaction notes

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