Sodium hydride → HCID 18470640, compound

HRID 1004006Notes

Reaction equation

HRID 1004006 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-f66942b1a6c842d8b6f288adb5780b07
Source dataset
uspto-grants-2000_04
Patent number
US06048864

Reaction notes

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