Triethylamine → HCID 86610629, compound

HRID 506385Notes

Reaction equation

HRID 506385 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(O)=O)=[CH:21][N:20]=2)[CH2:8][C@H:7]1[CH2:43][CH3:44])=[O:5])[CH3:2].C([N:47]([CH2:50]C)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:59])C=CC=CC=1.[C:69](=O)([O-])[OH:70].[Na+]>C1(C)C=CC=CC=1.C(OCC)(=O)C.CO>[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]([N:47]=[C:50]=[O:59])[C:22]([O:70][CH3:69])=[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:34])([F:35])[F:33])[CH:31]=3)[N:24]=2)[CH2:8][C@H:7]1[CH2:43][CH3:44])=[O:5])[CH3:2]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 516892Sodium BicarbonateHCID 86610553HCID 86610553, compound

Product 1

HCID 86610629HCID 86610629, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

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 (500 mg) is dissolved in toluene (10 ml), and thereto are added triethylamine (0.66 ml), diphenylphosphoryl azide (0.52 ml) and methanol (1 ml). The mixture is heated at 60° C. and stirred for 2 days. The reaction solution is cooled to room temperature, a saturated aqueous sodium hydrogen carbonate solution and ethyl acetate. The organic layer is washed with saturated brine and dried over magnesium sulfate, then 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-methoxy-carbonylaminopyrimidin-2-yl)}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (25 mg). MS (m/z): 657 [M+H]+.

Workup

  1. temperatureThe reaction solution is cooled to room temperature
  2. washThe organic layer is washed with saturated brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue is purified by column chromatography (silica gel; hexane:ethyl acetate=4:1→3:2)

Sources & evidence

ORD record
ord-1bbbcfb14eca4d6aad308968c47bf5fe
Source dataset
uspto-grants-2010_08
Patent number
US07781443B2

Reaction notes

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