Water → 8-benzyl-N-cyclobutyl-N-methyl-6,7,8,9-tetrahydropyrazino[2,3-f][1,4]oxazepin-3-amine

HRID 2188671Notes

Reaction equation

HRID 2188671 reaction equation
[CH2:1]([N:8]([CH2:12][C:13]1[C:18](Cl)=[N:17][C:16]([N:20]([CH:22]2[CH2:25][CH2:24][CH2:23]2)[CH3:21])=[CH:15][N:14]=1)[CH2:9][CH2:10][OH:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(C)([O-])C.[K+].O>CN(C=O)C>[CH2:1]([N:8]1[CH2:12][C:13]2[N:14]=[CH:15][C:16]([N:20]([CH:22]3[CH2:25][CH2:24][CH2:23]3)[CH3:21])=[N:17][C:18]=2[O:11][CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 962WaterHCID 23665647Potassium tert-butoxideHCID 866489982-[Benzyl({3-chloro-5-[cyclobutyl(methyl)amino]pyrazin-2-yl}methyl)amino]ethanol

Product 1

HCID 669931108-benzyl-N-cyclobutyl-N-methyl-6,7,8,9-tetrahydropyrazino[2,3-f][1,4]oxazepin-3-amineYield 72.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-[benzyl({3-chloro-5-[cyclobutyl(methyl)amino]pyrazin-2-yl}methyl)amino]ethanol (0.74 g) in DMF (4 mL) was added potassium tert-butoxide (0.28 g) at 0° C., and the mixture was stirred for 2 hr. Water (10 mL) was added, and the mixture was extracted with ethyl acetate. The aqueous layer was extracted again with ethyl acetate. The combined organic layer was washed with water and saturated brine, dried over magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography (solvent gradient: 10→40% ethyl acetate/hexane) to give the title compound (0.48 g, 71%) as a pale-yellow oil.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. extractionThe aqueous layer was extracted again with ethyl acetate
  3. washThe combined organic layer was washed with water and saturated brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel column chromatography (solvent gradient: 10→40% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-fb4e7ed6e1e94259b7acb4c6f8845acf
Source dataset
uspto-grants-2012_12
Patent number
US08324201B2

Reaction notes

Loading…