Morpholine → HCID 86610552, compound

HRID 506333Notes

Reaction equation

HRID 506333 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]([C:40](O)=[O:41])=[CH:21][N:20]=2)[CH2:8][C@H:7]1[CH2:43][CH3:44])=[O:5])[CH3:2].[NH:45]1[CH2:50][CH2:49][O:48][CH2:47][CH2:46]1.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(=O)([O-])O.[Na+]>CN(C)C=O.C(N(CC)CC)C>[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:37])([F:39])[F:38])[CH:29]=[C:30]([C:32]([F:33])([F:34])[F:35])[CH:31]=3)[C:22]([C:40]([N:45]3[CH2:50][CH2:49][O:48][CH2:47][CH2:46]3)=[O:41])=[CH:21][N:20]=2)[CH2:8][C@H:7]1[CH2:43][CH3:44])=[O:5])[CH3:2]

Participants

8

Reactant 5

HCID 8083MorpholineHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86610553HCID 86610553, compound

Product 1

HCID 86610552HCID 86610552, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

(2R*,4S*)-4-{[3,5-Bis(trifluoromethyl)benzyl]-(5-carboxypyrimidin-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 (4 ml) and thereto are added morpholine (0.03 ml) and 1-hydroxybenzotriazole (50 mg) at room temperature. 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide monohydrochloride (70 mg) is added to the mixture under ice-cooling, triethylamine (0.04 ml) is added thereto dropwise, and the mixture is stirred at room temperature overnight. 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=4:1→1:1) to give (2R*,4S*)-4-{[3,5-bis(trifluoromethyl)benzyl]-[5-(morpholin-4-carbonyl) pyrimidin-2-yl]}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (142 mg). MS (m/z): 697 [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; hexane:ethyl acetate=4:1→1:1)

Sources & evidence

ORD record
ord-89bc21550dd841adb29e50372db28837
Source dataset
uspto-grants-2010_08
Patent number
US07781443B2

Reaction notes

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