Triethylamine → HCID 86610583, compound

HRID 506352Notes

Reaction equation

HRID 506352 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]([C:40](O)=[O:41])=[CH:21][N:20]=2)[CH2:8][C@H:7]1[CH2:43][CH3:44])=[O:5])[CH3:2].ClC(OCC)=O.C(N(CC)CC)C>O1CCCC1>[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:39])([F:37])[F:38])[CH:29]=[C:30]([C:32]([F:33])([F:34])[F:35])[CH:31]=3)[C:22]([CH2:40][OH:41])=[CH:21][N:20]=2)[CH2:8][C@H:7]1[CH2:43][CH3:44])=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 86610553HCID 86610553, compound

Product 1

HCID 86610583HCID 86610583, compoundYield 81.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(2R*,4S*)-4-{[3,5-Bis(trifluoromethyl)benzyl]-(5-carboxypyrimidin-2-yl)}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (100 mg) is dissolved in tetrahydrofuran (2 ml), then thereto are added ethyl chloroformate (0.02 ml) and triethylamine (0.04 ml) under ice-cooling, and the mixture is stirred for 30 minutes. The reaction solution is filtered, sodium borohydride (18 mg) is added to the filtrate, and the mixture is stirred for 1 hour and 40 minutes. To the reaction solution is added 1N-hydrochloric acid and the mixture is extracted with ethyl acetate. The organic layer is washed successively with water, a saturated aqueous sodium hydrogen carbonate solution and 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-(hydroxymethyl)pyrimidin-2-yl]}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (80 mg). MS (m/z): 614 [M+H]+

Workup

  1. temperaturecooling
  2. filtrationThe reaction solution is filtered
  3. additionsodium borohydride (18 mg) is added to the filtrate
  4. stirringthe mixture is stirred for 1 hour and 40 minutes
  5. additionTo the reaction solution is added 1N-hydrochloric acid
  6. extractionthe mixture is extracted with ethyl acetate
  7. washThe organic layer is washed successively with water
  8. dry with materiala saturated aqueous sodium hydrogen carbonate solution and a saturated brine, dried over magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe resulting residue is purified by column chromatography (silica gel; hexane: ethyl acetate=4:1→3:2)

Sources & evidence

ORD record
ord-397d3ea00c5a4ad4af069d32f55ae6a5
Source dataset
uspto-grants-2010_08
Patent number
US07781443B2

Reaction notes

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