Triethylamine → HCID 86610590, compound

HRID 506359Notes

Reaction equation

HRID 506359 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]([CH:40]=[CH:41][C:42](O)=[O:43])=[CH:21][N:20]=2)[CH2:8][C@H:7]1[CH2:45][CH3:46])=[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:31]=[C:30]([C:32]([F:35])([F:33])[F:34])[CH:29]=[C:28]([C:36]([F:37])([F:38])[F:39])[CH:27]=3)[C:22]([CH:40]=[CH:41][CH2:42][OH:43])=[CH:21][N:20]=2)[CH2:8][C@H:7]1[CH2:45][CH3:46])=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 86610589HCID 86610589, compound

Product 1

HCID 86610590HCID 86610590, compoundYield 79.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(2R,4S)-4-{[3,5-Bis(trifluoromethyl)benzyl]-[5-(2-carboxyvinyl)pyrimidin-2-yl]}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (200 mg) is dissolved in tetrahydrofuran (4 ml), then thereto are added ethyl chloroformate (0.04 ml) and triethylamine (0.06 ml) under ice-cooling, and the mixture is stirred for 30 minutes. The reaction solution is filtered, then thereto is added sodium borohydride (58 mg), and the mixture is stirred for 1 hour and 30 minutes under ice-cooling. 1N-Hydrochloric acid is added to the reaction solution and the mixture is extracted with ethyl acetate. The organic layer is washed with water, a saturated aqueous sodium hydrogen carbonate solution and a saturated brine successively, 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-(3-hydroxypropenyl)pyrimidin-2-yl]}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (155 mg). MS (m/z): 640 [M+H]+

Workup

  1. temperaturecooling
  2. filtrationThe reaction solution is filtered
  3. additionis added sodium borohydride (58 mg)
  4. stirringthe mixture is stirred for 1 hour and 30 minutes under ice-
  5. temperaturecooling
  6. addition1N-Hydrochloric acid is added to the reaction solution
  7. extractionthe mixture is extracted with ethyl acetate
  8. washThe organic layer is washed with water
  9. dry with materiala saturated aqueous sodium hydrogen carbonate solution and a saturated brine successively, dried over magnesium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customThe resulting residue is purified by column chromatography (silica gel; hexane: ethyl acetate=4:1→3:2)

Sources & evidence

ORD record
ord-7a11843b847c471e9c5ec11d9362e0f9
Source dataset
uspto-grants-2010_08
Patent number
US07781443B2

Reaction notes

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