Morpholine → HCID 86610588, compound

HRID 506357Notes

Reaction equation

HRID 506357 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[H-].[Na+].[CH2:9]([O:11][C:12]([N:14]1[C:23]2[C:18](=[N:19][C:20]([O:24][CH3:25])=[CH:21][CH:22]=2)[C@@H:17]([NH:26][C:27]2[N:32]=[C:31]([CH2:33][C:34]3[CH:39]=[C:38]([C:40]([F:43])([F:42])[F:41])[CH:37]=[C:36]([C:44]([F:47])([F:46])[F:45])[CH:35]=3)[C:30]([CH2:48]Br)=[CH:29][N:28]=2)[CH2:16][C@H:15]1[CH2:50][CH3:51])=[O:13])[CH3:10].C(=O)([O-])O.[Na+]>CN(C)C=O>[CH2:9]([O:11][C:12]([N:14]1[C:23]2[C:18](=[N:19][C:20]([O:24][CH3:25])=[CH:21][CH:22]=2)[C@@H:17]([NH:26][C:27]2[N:32]=[C:31]([CH2:33][C:34]3[CH:39]=[C:38]([C:40]([F:41])([F:42])[F:43])[CH:37]=[C:36]([C:44]([F:45])([F:46])[F:47])[CH:35]=3)[C:30]([CH2:48][N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)=[CH:29][N:28]=2)[CH2:16][C@H:15]1[CH2:50][CH3:51])=[O:13])[CH3:10]

Participants

6

Reactant 4

HCID 8083MorpholineHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 86610587HCID 86610587, compound

Product 1

HCID 86610588HCID 86610588, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Morpholine (0.02 ml) is dissolved in N,N-dimethylformamide (2 ml), then thereto is added sodium hydride (9 mg) under ice-cooling, and the mixture is stirred for 30 minutes. (2R*,4S*)-4-{[3,5-Bis(trifluoromethyl)benzyl]-[5-(bromomethyl)pyrimidin-2-yl]}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (112 mg) is added to the reaction solution under ice-cooling, and the mixture is stirred at room temperature for 1 hour and 30 minutes. A saturated aqueous sodium hydrogen carbonate solution is added to the reaction solution and the mixture is extracted with ethyl acetate. The organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by column chromatography (silica gel; hexane: ethyl acetate=3:1→1:1) to give (2R*,4S*)-4-([3,5-bis(trifluoromethyl)benzyl]-{5-[(morpholin-4-yl)methyl]pyrimidin-2-yl})amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (33 mg). MS (m/z): 683 [M+H]+

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. stirringthe mixture is stirred at room temperature for 1 hour and 30 minutes
  4. extractionthe mixture is extracted with ethyl acetate
  5. washThe organic layer is washed with a saturated brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting residue is purified by column chromatography (silica gel; hexane: ethyl acetate=3:1→1:1)

Sources & evidence

ORD record
ord-015190979c67431c89a258380deaee30
Source dataset
uspto-grants-2010_08
Patent number
US07781443B2

Reaction notes

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