Sodium hydride → HCID 86610585, compound

HRID 506354Notes

Reaction equation

HRID 506354 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]([CH2:40][OH:41])=[CH:21][N:20]=2)[CH2:8][C@H:7]1[CH2:42][CH3:43])=[O:5])[CH3:2].[H-].[Na+].Br[CH2:47][CH2:48][O:49][CH:50]1[CH2:55][CH2:54][CH2:53][CH2:52][O:51]1.C(=O)([O-])O.[Na+]>CN(C)C=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:27]=[C:28]([C:36]([F:37])([F:38])[F:39])[CH:29]=[C:30]([C:32]([F:35])([F:33])[F:34])[CH:31]=3)[C:22]([CH2:40][O:41][CH2:47][CH2:48][O:49][CH:50]3[CH2:55][CH2:54][CH2:53][CH2:52][O:51]3)=[CH:21][N:20]=2)[CH2:8][C@H:7]1[CH2:42][CH3:43])=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 24758Sodium hydride2×HCID 866212-(2-Bromoethoxy)tetrahydro-2H-pyran2×HCID 516892Sodium BicarbonateHCID 86610583HCID 86610583, compound

Product 1

HCID 86610585HCID 86610585, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(2R*,4S*)-4-{[3,5-bis(trifluoromethyl)benzyl]-[5-(hydroxymethyl)pyrimidin-2-yl]}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (300 mg) is dissolved in N,N-dimethylformamide (4 ml), then thereto is added sodium hydride (28 mg) under ice-cooling, and the mixture is stirred for 30 minutes. 2-(2-Bromoethoxy)tetrahydropyran (0.15 ml) is added to the reaction solution, and the mixture is stirred at room temperature for 2 hours and 30 minutes. After addition of sodium hydride (28 mg) and 2-(2-bromoethoxy)-tetrahydropyran (0.15 ml), the mixture is stirred at 50° C. for 2 hours and 30 minutes. After cooling to room temperature, a saturated aqueous sodium hydrogen carbonate solution is added to the reaction solution, followed by extraction 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→3:2) to give (2R*,4S*)-4-[[3,5-bis(trifluoromethyl)benzyl]-(5-{2-[(tetrahydropyran-2-yl)oxy]ethoxymethyl}pyrimidin-2-yl)]amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (201 mg). MS (m/z): 742 [M+H]+

Workup

  1. temperaturecooling
  2. stirringthe mixture is stirred at room temperature for 2 hours and 30 minutes
  3. stirringthe mixture is stirred at 50° C. for 2 hours and 30 minutes
  4. extractionfollowed by extraction with ethyl acetate
  5. washThe organic layer is washed with a saturated brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting residue is purified by column chromatography (silica gel; hexane: ethyl acetate=4:1→3:2)

Sources & evidence

ORD record
ord-b1514097fc164c27b23292f58e4b8373
Source dataset
uspto-grants-2010_08
Patent number
US07781443B2

Reaction notes

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