Triphenylphosphine → (2R*,4S*)-4-{[3,5-bis(trifluoromethyl)benzyl]-[5-(pyrimidin-2-ylmethoxy)pyrimidin-2-yl]}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester

HRID 506345

Reaction equation

HRID 506345 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]([OH:40])=[CH:21][N:20]=2)[CH2:8][C@H:7]1[CH2:41][CH3:42])=[O:5])[CH3:2].[N:43]1[CH:48]=[CH:47][CH:46]=[N:45][C:44]=1[CH2:49]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.C1(C)C=CC=CC=1>O1CCCC1.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:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[C:28]([C:36]([F:38])([F:39])[F:37])[CH:27]=3)[C:22]([O:40][CH2:49][C:44]3[N:45]=[CH:46][CH:47]=[CH:48][N:43]=3)=[CH:21][N:20]=2)[CH2:8][C@H:7]1[CH2:41][CH3:42])=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 27630242-PyrimidinemethanolHCID 66777355Diethylazodicarboxylate tolueneHCID 86610574(2R*,4S*)-4-{[3,5-Bis(trifluoromethyl)benzyl]-(5-hydroxypyrimidin-2-yl)}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester

Product 1

HCID 86610575(2R*,4S*)-4-{[3,5-bis(trifluoromethyl)benzyl]-[5-(pyrimidin-2-ylmethoxy)pyrimidin-2-yl]}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl esterYield 68.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

(2R*,4S*)-4-{[3,5-Bis(trifluoromethyl)benzyl]-(5-hydroxypyrimidin-2-yl)}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (150 mg) is dissolved in tetrahydrofuran (1 ml), then thereto are added pyrimidin-2-ylmethanol (41 mg) and triphenylphosphine (98 mg). After adding dropwise 40% diethyl azodicarboxylate-toluene solution (163 μl) under ice-cooling, the mixture is stirred at room temperature for 1 hour and 30 minutes. 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; hexane:ethyl acetate=2:1) to give (2R*,4S*)-4-{[3,5-bis(trifluoromethyl)benzyl]-[5-(pyrimidin-2-ylmethoxy)pyrimidin-2-yl]}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (118 mg). MS (m/z): 692 [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=2:1)

Sources & evidence

ORD record
ord-7faf4db328664bbebad4f9dcc89d8dba
Source dataset
uspto-grants-2010_08
Patent number
US07781443B2

Linked notes

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