Morpholine → HCID 86610578, compound

HRID 506347Notes

Reaction equation

HRID 506347 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[N:11][C:12]([O:16][CH3:17])=[CH:13][CH:14]=2)[C@@H:9]([NH:18][C:19]2[N:24]=[C:23]([CH2:25][C:26]3[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[C:28]([C:36]([F:39])([F:38])[F:37])[CH:27]=3)[C:22]([O:40][CH2:41][C:42](O)=[O:43])=[CH:21][N:20]=2)[CH2:8][C@H:7]1[CH2:45][CH3:46])=[O:5])[CH3:2].[NH:47]1[CH2:52][CH2:51][O:50][CH2:49][CH2:48]1.Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1>CN(C)C=O.O>[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[N:11][C:12]([O:16][CH3:17])=[CH:13][CH:14]=2)[C@@H:9]([NH:18][C:19]2[N:24]=[C:23]([CH2:25][C:26]3[CH:27]=[C:28]([C:36]([F:39])([F:38])[F:37])[CH:29]=[C:30]([C:32]([F:33])([F:35])[F:34])[CH:31]=3)[C:22]([O:40][CH2:41][C:42]([N:47]3[CH2:52][CH2:51][O:50][CH2:49][CH2:48]3)=[O:43])=[CH:21][N:20]=2)[CH2:8][C@H:7]1[CH2:45][CH3:46])=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 8083MorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 86610576HCID 86610576, compound

Product 1

HCID 86610578HCID 86610578, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

(2R*,4S*)-4-{[3,5-Bis(trifluoromethyl)benzyl]-(5-carboxymethoxypyrimidin-2-yl)}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (150 mg) is dissolved in N,N-dimethylformamide (1 ml), then thereto is added morpholine (30 μl). After addition of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide monohydrochloride (66 mg) and 1-hydroxybenzotriazole hydrate (46 mg) under ice-cooling, the mixture is stirred at room temperature for 4 hours. Water is added to the reaction mixture 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; chloroform:methanol=19:1) to give (2R*,4S*)-4-([3,5-bis(trifluoromethyl)benzyl]-{5-[2-(morpholin-4-yl)-2-oxoethoxy]pyrimidin-2-yl})amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (138 mg). MS (m/z): 727 [M+H]+

Workup

  1. temperaturecooling
  2. extractionthe mixture is extracted with ethyl acetate
  3. washThe organic layer is washed with a saturated brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue is purified by column chromatography (silica gel; chloroform:methanol=19:1)

Sources & evidence

ORD record
ord-2526b0352d7344039133dcc82783acff
Source dataset
uspto-grants-2010_08
Patent number
US07781443B2

Reaction notes

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