4-Methylmorpholine → HCID 22856310, compound

HRID 264300Notes

Reaction equation

HRID 264300 reaction equation
Cl.[CH3:2][O:3][C:4]1[CH:9]=[CH:8][C:7]([S:10]([N:13]([CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C@H:14]([CH2:18][CH2:19][CH2:20][CH2:21][NH:22][C:23](=[O:28])[CH2:24][N:25]([CH3:27])[CH3:26])[C:15](O)=[O:16])(=[O:12])=[O:11])=[CH:6][CH:5]=1.O.[OH:37][N:38]1C2C=CC=CC=2N=N1.[CH3:47]N1CCOCC1.Cl.CN([CH2:58][CH2:59][CH2:60]N=C=NCC)C>C(Cl)Cl.CN(C)C=O>[C:59]([O:37][NH:38][C:15](=[O:16])[C@H:14]([N:13]([S:10]([C:7]1[CH:6]=[CH:5][C:4]([O:3][CH3:2])=[CH:9][CH:8]=1)(=[O:11])=[O:12])[CH2:29][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)[CH2:18][CH2:19][CH2:20][CH2:21][NH:22][C:23](=[O:28])[CH2:24][N:25]([CH3:27])[CH3:26])([CH3:60])([CH3:47])[CH3:58]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 70060004HCID 70060004, compound

Product 1

HCID 22856310HCID 22856310, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 2(R)-[[4-methoxybenzenesulfonyl](benzyl)amino]-6-[(N,N-dimethylglycyl)amino]hexanoic acid hydrochloride (4.12 g, 7.82 mmol) in methylene chloride (78 mL) and dimethylformamide (5 mL) is added 1-hydroxybenzotriazole monohydrate (1.26 g, 8.21 mmol), N-methylmorpholine (2.58 ml, 23.45 mmol), and O-t-butyhydroxylamine hydrochloride (1.08 g, 8.60 mmol). The reaction is cooled to 0° C., and N-[dimethylaminopropyl]-N'-ethylcarbodiimide hydrochloride (3.0 g, 15.64 mmol) is added. The reaction mixture is warmed to room temperature and stirred overnight. The mixture is then diluted with methylene chloride and washed with saturated aqueous sodium bicarbonate, and then with brine. The organic layer is dried (Na2SO4), filtered, and and the solvent is evaporated. The crude product is purified by silica gel chromatography (10/0.5/0.5 ethyl acetate/methanol/ammonium hydroxide) to provide N-(t-butyloxy)-2(R)-[[4-methoxybenzenesulfonyl](benzyl)amino]-6-[(N,N-dimethylglycyl)amino]hexanamide.

Workup

  1. temperatureThe reaction mixture is warmed to room temperature
  2. washwashed with saturated aqueous sodium bicarbonate
  3. dry with materialThe organic layer is dried (Na2SO4)
  4. filtrationfiltered
  5. customthe solvent is evaporated
  6. customThe crude product is purified by silica gel chromatography (10/0.5/0.5 ethyl acetate/methanol/ammonium hydroxide)

Sources & evidence

ORD record
ord-084335aa61694d15b4b67d4f80eec86c
Source dataset
uspto-grants-1997_07
Patent number
US05646167

Reaction notes

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