N-Piperidinoethanol → HCID 117598900, compound

HRID 522389Notes

Reaction equation

HRID 522389 reaction equation
[C:1]([C@H:5]1[C:32](=[O:33])[N:31]2[CH2:34][C@@H:28]([CH2:29][C@H:30]2[C:35]([NH:37][C@:38]2([C:43](=[O:51])[NH:44][S:45]([CH:48]3[CH2:50][CH2:49]3)(=[O:47])=[O:46])[CH2:40][C@H:39]2[CH:41]=[CH2:42])=[O:36])[O:27][C:17]2=[N:18][C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:24]=3[C:25]([OH:26])=[C:16]2[CH2:15][CH:14]=[CH:13][CH2:12][CH2:11][C@@H:10]2[CH2:52][CH2:53][CH2:54][C@H:9]2[O:8][C:7](=[O:55])[NH:6]1)([CH3:4])([CH3:3])[CH3:2].[N:56]1([CH2:62][CH2:63]O)[CH2:61][CH2:60][CH2:59][CH2:58][CH2:57]1.CP(C)C.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1.C(OCC)(=O)C.O>[C:1]([C@H:5]1[C:32](=[O:33])[N:31]2[CH2:34][C@@H:28]([CH2:29][C@H:30]2[C:35]([NH:37][C@:38]2([C:43](=[O:51])[NH:44][S:45]([CH:48]3[CH2:50][CH2:49]3)(=[O:46])=[O:47])[CH2:40][C@H:39]2[CH:41]=[CH2:42])=[O:36])[O:27][C:17]2=[N:18][C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:24]=3[C:25]([O:26][CH2:63][CH2:62][N:56]3[CH2:61][CH2:60][CH2:59][CH2:58][CH2:57]3)=[C:16]2[CH2:15][CH:14]=[CH:13][CH2:12][CH2:11][C@@H:10]2[CH2:52][CH2:53][CH2:54][C@H:9]2[O:8][C:7](=[O:55])[NH:6]1)([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 4

HCID 18232N-PiperidinoethanolHCID 68983TrimethylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 178455697HCID 178455697, compound

Product 1

HCID 117598900HCID 117598900, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (3aR,7S,10S,12R,21E,24aS)-7-tert-butyl-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 (synthesized by the method described in Example 17 with intermediates A1, B6, C3) (40 mg) in THF (0.8 mL) under nitrogen was added 2-(piperidin-1-yl)ethanol (0.137 mL), trimethylphosphine (1.028 mL) and diisopropylazodicarboxylate (0.200 mL). After stirring for 18 hours, the mixture was diluted with ethyl acetate and water was added. The mixture was extracted with ethyl acetate (3×). The combined organics were dried over magnesium sulfate, filtered and concentrated. Purification by reverse phase HPLC (30%-100% ACN/0.015% TFA-water) yielded 13.2 mg of the desired product. HRMS (ES+) m/z 889.4523 (M+H)+.

Workup

  1. additionwas added
  2. extractionThe mixture was extracted with ethyl acetate (3×)
  3. dry with materialThe combined organics were dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by reverse phase HPLC (30%-100% ACN/0.015% TFA-water)

Sources & evidence

ORD record
ord-9aad780d36c04337b12c512fa1aa3f0d
Source dataset
uspto-grants-2016_05
Patent number
US09328138B2

Reaction notes

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