Ethylene Glycol → (2R*,4S*)-4-([3,5-bis(trifluoromethyl)benzyl]-{5-[methyl-(2-hydroxyethyl)]-aminopyrimidin-2-yl})amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester

HRID 506336Notes

Reaction equation

HRID 506336 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](I)=[CH:21][N:20]=2)[CH2:8][C@H:7]1[CH2:41][CH3:42])=[O:5])[CH3:2].C(O)CO.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C[NH:56]CCO.[CH:60]([OH:63])([CH3:62])[CH3:61]>[Cu](I)I>[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:20]=[C:21]([NH2:56])[C:22]([CH2:61][CH:60]([CH3:62])[OH:63])=[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)[N:24]=2)[CH2:8][C@H:7]1[CH2:41][CH3:42])=[O:5])[CH3:2]

Participants

7

Reactant 5

HCID 174Ethylene GlycolHCID 3776IsopropanolHCID 80162-(Methylamino)ethanolHCID 62657Potassium Phosphate, TribasicHCID 86610559(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

Product 1

HCID 86610558(2R*,4S*)-4-([3,5-bis(trifluoromethyl)benzyl]-{5-[methyl-(2-hydroxyethyl)]-aminopyrimidin-2-yl})amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 83717Copper iodideCatalyst

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 (200 mg) is dissolved in isopropanol (1 ml), then thereto are added copper iodide (2.7 mg), ethylene glycol (31 μl), potassium phosphate (119 mg) and 2-methylaminoethanol (20 μl), and the mixture is heated to 80° C. under nitrogen flow, and stirred for 20 hours. 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 (silica gel; hexane:ethyl acetate=9:1→3:7) to give (2R*,4S*)-4-([3,5-bis(trifluoromethyl)benzyl]-{5-[methyl-(2-hydroxyethyl)]-aminopyrimidin-2-yl})amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (58.2 mg). MS (m/z): 657 [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 (silica gel; hexane:ethyl acetate=9:1→3:7)

Sources & evidence

ORD record
ord-5f685fcca8fb45f287398ea151ad3be6
Source dataset
uspto-grants-2010_08
Patent number
US07781443B2

Reaction notes

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