Triethylamine → tert-butyl ((S)-1-{2-[5-fluoro-3-(4-methoxyphenyl)-4-oxo-8-propoxy-4H-quinolin-1-yl]ethylcarbamoyl}-2-hydroxyethyl)carbamate

HRID 1874048Notes

Reaction equation

HRID 1874048 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:12]([OH:14])=O)[CH2:10][OH:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.P(C#N)(=O)(OCC)OCC.[NH2:32][CH2:33][CH2:34][N:35]1[C:44]2[C:39](=[C:40]([F:49])[CH:41]=[CH:42][C:43]=2[O:45][CH2:46][CH2:47][CH3:48])[C:38](=[O:50])[C:37]([C:51]2[CH:56]=[CH:55][C:54]([O:57][CH3:58])=[CH:53][CH:52]=2)=[CH:36]1>O.CN(C=O)C>[C:1]([O:5][C:6](=[O:7])[NH:8][C@H:9]([C:12](=[O:14])[NH:32][CH2:33][CH2:34][N:35]1[C:44]2[C:39](=[C:40]([F:49])[CH:41]=[CH:42][C:43]=2[O:45][CH2:46][CH2:47][CH3:48])[C:38](=[O:50])[C:37]([C:51]2[CH:52]=[CH:53][C:54]([O:57][CH3:58])=[CH:55][CH:56]=2)=[CH:36]1)[CH2:10][OH:11])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 76257Diethyl cyanophosphonateHCID 98766N-[tert-butoxycarbonyl]-L-serineHCID 58492395HCID 58492395, compound

Product 1

HCID 68207133tert-butyl ((S)-1-{2-[5-fluoro-3-(4-methoxyphenyl)-4-oxo-8-propoxy-4H-quinolin-1-yl]ethylcarbamoyl}-2-hydroxyethyl)carbamateYield 75%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent3×

Procedure

A DMF solution (0.5 ml) of N-(tert-butoxycarbonyl)-L-serine (174 mg, 0.85 mmol), triethylamine (198 mg, 1.96 mmol), diethyl phosphorocyanidate (DEPC, 176 mg, 0.97 mmol) and DMF (0.5 ml) were sequentially added to a DMF solution (1 ml) of 1-(2-aminoethyl)-5-fluoro-3-(4-methoxyphenyl)-8-propoxy-1H-quinolin-4-one (300 mg, 0.81 mmol) while ice-cooling, and stirred at room temperature for 20 hours. Water was added to the reaction mixture and then subjected to extraction using ethyl acetate. The thus-obtained organic layer was washed with an aqueous saturated sodium chloride solution twice. The washed product was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was purified using silica gel column chromatography (dichloromethane:methanol=40:1→30:1). The purified product was concentrated to dryness under reduced pressure, giving a white amorphous solid of tert-butyl((S)-1-{2-[5-fluoro-3-(4-methoxyphenyl)-4-oxo-8-propoxy-4H-quinolin-1-yl]ethylcarbamoyl}-2-hydroxyethyl)carbamate (338 mg, yield: 75%).

Workup

  1. temperaturecooling
  2. extractionsubjected to extraction
  3. washThe thus-obtained organic layer was washed with an aqueous saturated sodium chloride solution twice
  4. dry with materialThe washed product was dried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified
  7. concentrationThe purified product was concentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-e73a42cd486241aeb144d2e4bfecee07
Source dataset
uspto-grants-2012_11
Patent number
US08304546B2

Reaction notes

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