Cesium carbonate → (3aR,7S,10S,12R,21E,24aS)-7-cyclopentyl-N-{(1R,2S)-1-[(cyclopropylsulfonyl)carbamoyl]-2-ethenylcyclopropyl}-5,8-dioxo-19-[2-(2-oxo-1,3-oxazolidin-3-yl)ethoxy]-1,2,3,3a,5,6,7,8,11,12,20,23,24,24a-tetradecahydro-10H-9,12-methanocyclopenta[18,19][1,10,3,6]dioxadiazacyclononadecino[11,12-b]quinoline-10-carboxamide

HRID 522384Notes

Reaction equation

HRID 522384 reaction equation
[CH:1]1([C@H:6]2[C:33](=[O:34])[N:32]3[CH2:35][C@@H:29]([CH2:30][C@H:31]3[C:36]([NH:38][C@:39]3([C:44](=[O:52])[NH:45][S:46]([CH:49]4[CH2:51][CH2:50]4)(=[O:48])=[O:47])[CH2:41][C@H:40]3[CH:42]=[CH2:43])=[O:37])[O:28][C:18]3=[N:19][C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][C:25]=4[C:26]([OH:27])=[C:17]3[CH2:16][CH:15]=[CH:14][CH2:13][CH2:12][C@@H:11]3[CH2:53][CH2:54][CH2:55][C@H:10]3[O:9][C:8](=[O:56])[NH:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1C=CC(S(O[CH2:74][CH2:75][N:76]2[CH2:80][CH2:79][O:78][C:77]2=[O:81])(=O)=O)=CC=1>CN(C=O)C>[CH:1]1([C@H:6]2[C:33](=[O:34])[N:32]3[CH2:35][C@@H:29]([CH2:30][C@H:31]3[C:36]([NH:38][C@:39]3([C:44](=[O:52])[NH:45][S:46]([CH:49]4[CH2:50][CH2:51]4)(=[O:47])=[O:48])[CH2:41][C@H:40]3[CH:42]=[CH2:43])=[O:37])[O:28][C:18]3=[N:19][C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][C:25]=4[C:26]([O:27][CH2:74][CH2:75][N:76]4[CH2:80][CH2:79][O:78][C:77]4=[O:81])=[C:17]3[CH2:16][CH:15]=[CH:14][CH2:13][CH2:12][C@@H:11]3[CH2:53][CH2:54][CH2:55][C@H:10]3[O:9][C:8](=[O:56])[NH:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 157609472-(2-Oxooxazolidin-3-yl)ethyl 4-methylbenzenesulfonateHCID 178455696HCID 178455696, compound

Product 1

HCID 117598933(3aR,7S,10S,12R,21E,24aS)-7-cyclopentyl-N-{(1R,2S)-1-[(cyclopropylsulfonyl)carbamoyl]-2-ethenylcyclopropyl}-5,8-dioxo-19-[2-(2-oxo-1,3-oxazolidin-3-yl)ethoxy]-1,2,3,3a,5,6,7,8,11,12,20,23,24,24a-tetradecahydro-10H-9,12-methanocyclopenta[18,19][1,10,3,6]dioxadiazacyclononadecino[11,12-b]quinoline-10-carboxamideYield 85.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of (3aR,7S,10S,12R,21E,24aS)-7-cyclopentyl-N-{(1R,2S)-1-[(cyclopropylsulfonyl)carbamoyl]-2-ethenylcyclopropyl}-19-hydroxy-5,8-dioxo-1,2,3,3a,5,6,7,8,11,12,20,23,24,24a-tetradecahydro-10H-9,12-methanocyclopenta[18,19][1,10,3,6]dioxadiazacyclononadecino[11,12-b]quinoline-10-carboxamide (Example 17) (40 mg) in DMF (0.75 mL) under nitrogen was added cesium carbonate (495 mg) followed by 2-(2-oxo-1,3-oxazolidin-3-yl)ethyl 4-methylbenzenesulfonate (144 mg). The reaction mixture was stirred at room temperature for 30 minutes and at 50° C. for 3 hours. After cooling back to room temperature, the reaction was quenched with water and extracted with ethyl acetate (3×). The combined organic fractions were dried over magnesium sulfate, filtered and concentrated. Purification by reverse phase HPLC (40%-100% ACN/0.15% TFA-water) afforded the desired product (39 mg) after workup with NaHCO3 and ethyl acetate. HRMS (ES+) m/z 903.3933 (M+H)+.

Workup

  1. temperatureAfter cooling back to room temperature
  2. customthe reaction was quenched with water
  3. extractionextracted with ethyl acetate (3×)
  4. dry with materialThe combined organic fractions were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by reverse phase HPLC (40%-100% ACN/0.15% TFA-water)

Sources & evidence

ORD record
ord-58aea13277e4401ea4e5365f61674940
Source dataset
uspto-grants-2016_05
Patent number
US09328138B2

Reaction notes

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