Sodium hydride → HCID 18470640, compound

HRID 2228494Notes

Reaction equation

HRID 2228494 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:13][CH3:14])=[C:9]([OH:12])[CH:10]=2)[N:5]=[C:4]([N:15]2[CH2:21][CH2:20][CH2:19][N:18]([C:22]([N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)=[O:23])[CH2:17][CH2:16]2)[CH:3]=1.[CH:30]1(Br)[CH2:33][CH2:32][CH2:31]1.[H-].[Na+]>CN(C)C=O>[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:13][CH3:14])=[C:9]([O:12][CH:30]3[CH2:33][CH2:32][CH2:31]3)[CH:10]=2)[N:5]=[C:4]([N:15]2[CH2:21][CH2:20][CH2:19][N:18]([C:22]([N:24]3[CH2:25][CH2:26][O:27][CH2:28][CH2:29]3)=[O:23])[CH2:17][CH2:16]2)[CH:3]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 78110BromocyclobutaneHCID 18470651HCID 18470651, compound

Product 1

HCID 18470640HCID 18470640, compoundYield 35.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

4-Amino-6-hydroxy-7-methoxy-2-[4-(4-morpholinecarbonyl)-1,4-diazepan-1-yl]quinoline (200 mg, 0.0005 mol) and cyclobutyl bromide (75 mg, 0.00055 mol) were added to a suspension of sodium hydride (20 mg, 0.0005 mol) in dimethylformamide (5 ml), and the reaction stirred under a nitrogen atmosphere at 50° C. for 18 hours. On cooling, the mixture was partitioned between ethyl acetate (15 ml) and water (15 ml), and the aqueous layer further extracted with ethyl acetate (30 ml). The combined organic extracts were dried (MgSO4), filtered and evaporated under reduced pressure. The crude product was purified on silica gel eluting with a solvent gradient of 0.880 aqueous ammonia: methanol:dichloromethane (0:0:100 to 1:10:90 v/v) to give the title compound as a foam (80 mg, 35%). Rf 0.65 (0.880 aqueous ammonia:methanol:dichloromethane 2:14:84, v/v). MS m/z 456 (MH)+. Found: C, 56.54; H, 6.60; N, 13.83; C24H33N5O4 0.6 CH2Cl2 0.8 H2O, requires C, 56.72; H, 6.93; N, 13.44%.

Workup

  1. temperatureOn cooling
  2. customthe mixture was partitioned between ethyl acetate (15 ml) and water (15 ml)
  3. extractionthe aqueous layer further extracted with ethyl acetate (30 ml)
  4. dry with materialThe combined organic extracts were dried (MgSO4)
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customThe crude product was purified on silica gel eluting with a solvent gradient of 0.880 aqueous ammonia: methanol:dichloromethane (0:0:100 to 1:10:90 v/v)

Sources & evidence

ORD record
ord-869fd1e7a3944c5a8affe1ccb76b5752
Source dataset
uspto-grants-2002_07
Patent number
US06417194B1

Reaction notes

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