Piperidine → (7S,14S,18S)-tri-tert-butyl 7-amino-1-(1-(2-(bis(2-tert-butoxy-2-oxo ethyl)amino)-2-oxo ethyl)-1H-imidazol-2-yl)-2-((1-(2-(bis(2-tert-butoxy-2-oxo ethyl)amino)-2-oxo ethyl)-1H-imidazol-2-yl)methyl)-8,16-dioxo-2,9,15,17-tetraazaicosane-14,18,20-tricarboxylate

HRID 56331Notes

Reaction equation

HRID 56331 reaction equation
[C:1]([O:5][C:6](=[O:112])[CH2:7][N:8]([CH2:104][C:105](=[O:111])[O:106][C:107]([CH3:110])([CH3:109])[CH3:108])[C:9](=[O:103])[CH2:10][N:11]1[CH:15]=[CH:14][N:13]=[C:12]1[CH2:16][N:17]([CH2:77][C:78]1[N:79]([CH2:83][C:84](=[O:102])[N:85]([CH2:94][C:95](=[O:101])[O:96][C:97]([CH3:100])([CH3:99])[CH3:98])[CH2:86][C:87](=[O:93])[O:88][C:89]([CH3:92])([CH3:91])[CH3:90])[CH:80]=[CH:81][N:82]=1)[CH2:18][CH2:19][CH2:20][CH2:21][C@@H:22]([C:41](=[O:76])[NH:42][CH2:43][CH2:44][CH2:45][CH2:46][C@@H:47]([C:69]([O:71][C:72]([CH3:75])([CH3:74])[CH3:73])=[O:70])[NH:48][C:49](=[O:68])[NH:50][C@H:51]([C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])[CH2:52][CH2:53][C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[NH:23]C(=O)OCC1C2C=CC=CC=2C2C1=CC=CC=2)([CH3:4])([CH3:3])[CH3:2].N1CCCCC1>CN(C=O)C>[NH2:23][C@H:22]([C:41](=[O:76])[NH:42][CH2:43][CH2:44][CH2:45][CH2:46][C@@H:47]([C:69]([O:71][C:72]([CH3:75])([CH3:74])[CH3:73])=[O:70])[NH:48][C:49](=[O:68])[NH:50][C@H:51]([C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])[CH2:52][CH2:53][C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[CH2:21][CH2:20][CH2:19][CH2:18][N:17]([CH2:77][C:78]1[N:79]([CH2:83][C:84]([N:85]([CH2:86][C:87]([O:88][C:89]([CH3:90])([CH3:91])[CH3:92])=[O:93])[CH2:94][C:95](=[O:101])[O:96][C:97]([CH3:98])([CH3:99])[CH3:100])=[O:102])[CH:80]=[CH:81][N:82]=1)[CH2:16][C:12]1[N:11]([CH2:10][C:9]([N:8]([CH2:104][C:105]([O:106][C:107]([CH3:109])([CH3:108])[CH3:110])=[O:111])[CH2:7][C:6](=[O:112])[O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:103])[CH:15]=[CH:14][N:13]=1

Participants

4

Reactant 2

HCID 8082PiperidineHCID 86643307(5S,12S,16S)-tri-tert-butyl 5-(4-(bis((1-(2-(bis(2-tert-butoxy-2-oxo ethyl)amino)-2-oxo ethyl)-1H-imidazol-2-yl)methyl)amino)butyl)-1-(9H-fluoren-9-yl)-3,6,14-trioxo-2-oxa-4,7,13,15-tetraazaoctadecane-12,16,18-tricarboxylate

Product 1

HCID 59404258(7S,14S,18S)-tri-tert-butyl 7-amino-1-(1-(2-(bis(2-tert-butoxy-2-oxo ethyl)amino)-2-oxo ethyl)-1H-imidazol-2-yl)-2-((1-(2-(bis(2-tert-butoxy-2-oxo ethyl)amino)-2-oxo ethyl)-1H-imidazol-2-yl)methyl)-8,16-dioxo-2,9,15,17-tetraazaicosane-14,18,20-tricarboxylateYield 25%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of the above product, (5S,12S,16S)-tri-tert-butyl 5-(4-(bis((1-(2-(bis(2-tert-butoxy-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)amino)butyl)-1-(9H-fluoren-9-yl)-3,6,14-trioxo-2-oxa-4,7,13,15-tetraazaoctadecane-12,16,18-tricarboxylate in DMF (1.0 mL) was added piperidine (0.50 mL). The mixture was stirred at room temperature for 2 hrs. Solvent was evaporated under reduce pressure to afford a residue, which was purified by biotage eluting with 5% MeOH to 50% MeOH in DCM to afford (7S,14S,18S)-tri-tert-butyl 7-amino-1-(1-(2-(bis(2-tert-butoxy-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)-2-((1-(2-(bis(2-tert-butoxy-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)-8,16-dioxo-2,9,15,17-tetraazaicosane-14,18,20-tricarboxylate (40 mg, 25%) as a white solid. 1H NMR (400 MHz, CDCl3) 6.96 (s, 2H), 6.83 (d, 2H), 6.37 (brs, 1H), 6.33 (brs, 1H), 5.05 (s, 4H), 4.87 (brs, 2H), 4.27-4.24 (m, 2H), 4.18 (s, 4H), 4.10 (s, 4H), 3.88 (d, J=15.2 Hz, 2H), 3.62 (d, J=15.2 Hz, 2H), 3.14-3.12 (m, 1H), 2.30-1.24 (m, 83H); MS (ESI), 674.1 (M/2+H)+.

Workup

  1. customSolvent was evaporated
  2. customto afford a residue, which
  3. customwas purified by biotage
  4. washeluting with 5% MeOH to 50% MeOH in DCM

Sources & evidence

ORD record
ord-0241e27be9fb4bcfb651db34294f5501
Source dataset
uspto-grants-2016_09
Patent number
US09433594B2

Reaction notes

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