Azepane → HCID 86589037, compound

HRID 1374766Notes

Reaction equation

HRID 1374766 reaction equation
[H-].C([Al+]CC(C)C)C(C)C.C(O[C:14]([C:16]1[CH:25]=[C:24]2[C:19]([C:20](Cl)=[CH:21][C:22]([Cl:26])=[N:23]2)=[CH:18][C:17]=1[CH3:28])=[O:15])C.S([O-])([O-])(=O)=O.[Mg+2].[NH:35]1[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]1.[Cl-].[Li+]>O1CCCC1.C(OCC)(=O)C>[N:35]1([C:20]2[C:19]3[C:24](=[CH:25][C:16]([CH2:14][OH:15])=[C:17]([CH3:28])[CH:18]=3)[N:23]=[C:22]([Cl:26])[CH:21]=2)[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]1

Participants

8

Reactant 5

HCID 8119AzepaneHCID 24083Sulfuric acid magnesium salt (1:1)HCID 433294Lithium ChlorideHCID 21225700DiisobutylaluminumhydrideHCID 86218311HCID 86218311, compound

Product 1

HCID 86589037HCID 86589037, compoundYield 66.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

Diisobutylaluminum hydride (1 M in tetrahydrofuran, 4.9 mL, 4.9 mmol) was added dropwise to a solution of 2,4-dichloro-6-methyl-quinoline-7-carboxylic acid ethyl ester (example 81c, 200 mg, 0.704 mmol) in tetrahydrofuran (10 mL), then after 20 min the reaction was stopped by addition of 2.5 M aq. magnesium sulfate solution (2 mL). The precipitate that formed after a few seconds was removed by filtration, and the filtrate was washed with brine, dried (MgSO4), and evaporated. The residue ((2,4-dichloro-6-methyl-quinolin-7-yl)-methanol) was dissolved in 1-methylpyrrolidin-2-one (3 mL), then azepane (349 mg, 3.52 mmol) and lithium chloride (119 mg, 2.82 mmol) were added, and the solution was heated at 80° C. for 16 h. After cooling ethyl acetate was added and the solution was washed with sat. aq. ammonium chloride solution and brine, dried (MgSO4), and evaporated. Flash chromatography (SiO2, hexane/ethyl acetate gradient) yielded the title compound (142 mg, 66%). Off-white solid, ISP-MS: m/e=305.3 ([M+H]+).

Workup

  1. customThe precipitate that formed after a few seconds
  2. customwas removed by filtration
  3. washthe filtrate was washed with brine
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. dissolutionThe residue ((2,4-dichloro-6-methyl-quinolin-7-yl)-methanol) was dissolved in 1-methylpyrrolidin-2-one (3 mL)
  7. additionwas added
  8. washthe solution was washed with sat. aq. ammonium chloride solution and brine
  9. dry with materialdried (MgSO4)
  10. customevaporated

Sources & evidence

ORD record
ord-2a82d5724a1944158d9e0736e3b91f46
Source dataset
uspto-grants-2007_01
Patent number
US07166589B2

Reaction notes

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