Pyridine → 83602-41-9

HRID 1714732Notes

Reaction equation

HRID 1714732 reaction equation
[CH3:1][CH2:2][C@@H:3]1[NH:46][C:44](=[O:45])[C@H:43]([C@H:47]([OH:54])[C@@H:48]([CH2:50]/[CH:51]=[CH:52]/[CH3:53])[CH3:49])[N:42]([CH3:55])[C:40](=[O:41])[C@H:39]([CH:56]([CH3:58])[CH3:57])[N:38]([CH3:59])[C:36](=[O:37])[C@H:35]([CH2:60][CH:61]([CH3:63])[CH3:62])[N:34]([CH3:64])[C:32](=[O:33])[C@H:31]([CH2:65][CH:66]([CH3:68])[CH3:67])[N:30]([CH3:69])[C:28](=[O:29])[C@@H:27]([CH3:70])[NH:26][C:24](=[O:25])[C@H:23]([CH3:71])[NH:22][C:20](=[O:21])[C@H:19]([CH2:72][CH:73]([CH3:75])[CH3:74])[N:18]([CH3:76])[C:16](=[O:17])[C@H:15]([CH:77]([CH3:79])[CH3:78])[NH:14][C:12](=[O:13])[C@H:11]([CH2:80][CH:81]([CH3:83])[CH3:82])[N:10]([CH3:84])[C:8](=[O:9])[CH2:7][N:6]([CH3:85])[C:4]1=[O:5].[C:86](OC(=O)C)(=[O:88])[CH3:87].N1C=CC=CC=1.C(=O)(O)[O-].[Na+]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH3:1][CH2:2][C@@H:3]1[NH:46][C:44](=[O:45])[C@H:43]([C@H:47]([O:54][C:86]([CH3:87])=[O:88])[C@@H:48]([CH2:50]/[CH:51]=[CH:52]/[CH3:53])[CH3:49])[N:42]([CH3:55])[C:40](=[O:41])[C@H:39]([CH:56]([CH3:57])[CH3:58])[N:38]([CH3:59])[C:36](=[O:37])[C@H:35]([CH2:60][CH:61]([CH3:62])[CH3:63])[N:34]([CH3:64])[C:32](=[O:33])[C@H:31]([CH2:65][CH:66]([CH3:68])[CH3:67])[N:30]([CH3:69])[C:28](=[O:29])[C@@H:27]([CH3:70])[NH:26][C:24](=[O:25])[C@H:23]([CH3:71])[NH:22][C:20](=[O:21])[C@H:19]([CH2:72][CH:73]([CH3:75])[CH3:74])[N:18]([CH3:76])[C:16](=[O:17])[C@H:15]([CH:77]([CH3:79])[CH3:78])[NH:14][C:12](=[O:13])[C@H:11]([CH2:80][CH:81]([CH3:83])[CH3:82])[N:10]([CH3:84])[C:8](=[O:9])[CH2:7][N:6]([CH3:85])[C:4]1=[O:5]

Participants

7

Reactant 4

HCID 1049PyridineHCID 7918Acetic AnhydrideHCID 516892Sodium BicarbonateHCID 5284373Cyclosporin A

Product 1

HCID 1516176283602-41-9Yield 95%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of cyclosporin A (5.0 g, 4.16 mmol), acetic anhydride (3.92 mL, 41.6 mmol), pyridine (3.36 mL, 41.6 mmol), and DMAP (0.5 g, 4.2 mmol) in methylene chloride (20 mL) was stirred overnight at room temperature under N2 atmosphere. Saturated sodium bicarbonate solution (200 mL) was added to the solution and stirred for an additional 2 h. The mixture was extracted with ether, washed with 1 N HCl, neutralized with saturated sodium bicarbonate solution, washed with brine, dried over sodium sulfate, and concentrated in vacuo to afford acetyl cyclosporin A (4.92 g, 95%) as a white solid, which was carried to the next step without further purification: 1H NMR (300 MHz, CDCl3) δ 8.57 (d, J=9.6 Hz, 1H), 8.04 (d, J=6.9 Hz, 1H), 7.51 (d, J=9.4 Hz, 1H), 7.47 (d, J=7.8 Hz, 1H), 5.67 (dd, J=11.0, 4.0 Hz, 1H), 5.60-5.44 (m, 2H), 5.39 (dd, J=11.7, 3.7 Hz, 1H), 5.32-5.13 (m, 4H), 5.06-4.93 (m, 2H), 4.85 (t, J=7.2 Hz, 1H), 4.77 (t, J=9.6 Hz, 1H), 4.65 (d, J=13.7 Hz, 1H), 4.41 (t, J=7.0 Hz, 1H), 3.46 (s, 3H), 3.26 (s, 3H), 3.24 (s, 3H), 3.21 (s, 3H), 3.10 (s, 3H), 2.68 (s, 3H), 2.66 (s, 3H), 2.50-2.35 (m, 1H), 2.25-1.80 (m, 6H), 2.08 (s, 3H), 2.01 (s, 3H), 1.75-1.55 (m, 6H), 1.45-0.75 (m, 55H); ESI MS m/z 1245 [C64H113N11O13+H]+.

Workup

  1. extractionThe mixture was extracted with ether
  2. washwashed with 1 N HCl
  3. washwashed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-14aee23e3e2849ae8743e0e1d1ed26a0
Source dataset
uspto-grants-2010_09
Patent number
US07799756B2

Reaction notes

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