Morpholine → HCID 86610613, compound

HRID 506379Notes

Reaction equation

HRID 506379 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[C:24]([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)=[N:23][CH:22]=[C:21](Cl)[N:20]=2)[CH2:8][C@H:7]1[CH2:41][CH3:42])=[O:5])[CH3:2].C(N(C(C)C)CC)(C)C.[NH:52]1[CH2:57][CH2:56][O:55][CH2:54][CH2:53]1>CN1CCN(C)C1=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[C:24]([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)=[N:23][CH:22]=[C:21]([N:52]3[CH2:57][CH2:56][O:55][CH2:54][CH2:53]3)[N:20]=2)[CH2:8][C@H:7]1[CH2:41][CH3:42])=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 86610614HCID 86610614, compound

Product 1

HCID 86610613HCID 86610613, compound

Reagents, catalysts & solvents 1

HCID 66611,3-Dimethyl-2-imidazolidinoneSolvent

Conditions

Temperature
100 °C

Procedure

(2R*,4S*)-4-{[3,5-Bis(trifluoromethyl)benzyl]-(6-chloropyrazin-2-yl)}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (300 mg) is dissolved in 1,3-dimethylimidazolidinone (2 ml), then thereto are added diisopropylethylamine (0.13 ml) and morpholine (0.6 ml), and the mixture is heated to 100° C. and stirred for 3 days. After adding distilled water, the mixture is extracted with ether. 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 (NH-silica gel; hexane: ethyl acetate=9:1→7:3) to give (2R*,4S*)-4-{[3,5-bis(trifluoromethyl)benzyl]-[6-(morpholin-4-yl)pyrazin-2-yl]}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (223.2 mg). MS (m/z): 669 [M+H]+

Workup

  1. additionAfter adding
  2. distillationdistilled water
  3. extractionthe mixture is extracted with ether
  4. washThe organic layer is washed with a saturated brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue is purified by column chromatography (NH-silica gel; hexane: ethyl acetate=9:1→7:3)

Sources & evidence

ORD record
ord-0af78b9a5e7943dba968b74ae52e96d6
Source dataset
uspto-grants-2010_08
Patent number
US07781443B2

Reaction notes

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