Ethylene Glycol → HCID 86610580, compound

HRID 506350Notes

Reaction equation

HRID 506350 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]([C:18]2[N:23]=[C:22]([CH2:24][C:25]3[CH:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=[C:27]([C:35]([F:38])([F:37])[F:36])[CH:26]=3)[C:21](I)=[CH:20][N:19]=2)[CH2:8][C@@:7]1([NH2:42])[CH2:40][CH3:41])=[O:5])[CH3:2].[SH:43][CH2:44][CH2:45][OH:46].C(O)CO.C(=O)([O-])[O-].[K+].[K+]>C(O)(C)C.[Cu](I)I.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]([C:18]2[N:23]=[C:22]([CH2:24][C:25]3[CH:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=[C:27]([C:35]([F:38])([F:37])[F:36])[CH:26]=3)[C:21]([S:43][CH2:44][CH2:45][OH:46])=[CH:20][N:19]=2)[CH2:8][C@@:7]1([NH2:42])[CH2:40][CH3:41])=[O:5])[CH3:2]

Participants

8

Reactant 4

HCID 174Ethylene GlycolHCID 15672-MercaptoethanolHCID 11430Potassium CarbonateHCID 86610581HCID 86610581, compound

Product 1

HCID 86610580HCID 86610580, compound

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 962WaterSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
80 °C

Procedure

(2R,4S)-4-{[3,5-Bis(trifluoromethyl)benzyl]-(5-iodopyrimidin-2-yl)}-amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (400 mg) is dissolved in isopropyl alcohol (2 ml), then thereto are added 2-mercaptoethanol (96 μl), copper iodide (20 mg), ethylene glycol (62 μl) and potassium carbonate (156 mg), and the mixture is stirred at 80° C. under nitrogen flow overnight. After cooling to room temperature, water is added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer is washed with a saturated brine twice, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by column chromatography (silica gel; hexane:ethyl acetate=2:1→1:1) to give (2R,4S)-4-{[3,5-bis(trifluoromethyl)benzyl]-[5-(2-hydroxyethylsulfanyl)pyrimidin-2-yl]}-amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (110 mg). MS (m/z): 660 [M+H]+

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer is washed with a saturated brine twice
  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=2:1→1:1)

Sources & evidence

ORD record
ord-763db348c15e4e0e8c81f119c68fc76e
Source dataset
uspto-grants-2010_08
Patent number
US07781443B2

Reaction notes

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