Piperidine → 2-methylalanyl-N-{(3R,4S,5S)-1-[(2S)-2-{(3R,4R,7S)-7-benzyl-4-methyl-18-[(4S,5R)-5-methyl-2-oxoimidazolidin-4-yl]-5,8,13-trioxo-2-oxa-6,9,12-triazaoctadecan-3-yl}pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl}-N-methyl-L-valinamide

HRID 74821Notes

Reaction equation

HRID 74821 reaction equation
C1C2C(COC([NH:18][C:19]([CH3:84])([C:21]([NH:23][C@H:24]([C:28]([N:30]([C@@H:32]([C@@H:80]([CH3:83])[CH2:81][CH3:82])[C@H:33]([O:78][CH3:79])[CH2:34][C:35]([N:37]3[CH2:41][CH2:40][CH2:39][C@H:38]3[C@@H:42]([C@@H:45]([CH3:77])[C:46](=[O:76])[NH:47][C@@H:48]([CH2:69][C:70]3[CH:75]=[CH:74][CH:73]=[CH:72][CH:71]=3)[C:49](=[O:68])[NH:50][CH2:51][CH2:52][NH:53][C:54](=[O:67])[CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][C@H:60]3[C@@H:64]([CH3:65])[NH:63][C:62](=[O:66])[NH:61]3)[O:43][CH3:44])=[O:36])[CH3:31])=[O:29])[CH:25]([CH3:27])[CH3:26])=[O:22])[CH3:20])=O)C3C(=CC=CC=3)C=2C=CC=1.N1CCCCC1>CN(C=O)C>[CH3:20][C:19]([C:21]([NH:23][C@H:24]([C:28]([N:30]([C@@H:32]([C@@H:80]([CH3:83])[CH2:81][CH3:82])[C@H:33]([O:78][CH3:79])[CH2:34][C:35]([N:37]1[CH2:41][CH2:40][CH2:39][C@H:38]1[C@@H:42]([C@@H:45]([CH3:77])[C:46](=[O:76])[NH:47][C@@H:48]([CH2:69][C:70]1[CH:75]=[CH:74][CH:73]=[CH:72][CH:71]=1)[C:49](=[O:68])[NH:50][CH2:51][CH2:52][NH:53][C:54](=[O:67])[CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][C@H:60]1[C@@H:64]([CH3:65])[NH:63][C:62](=[O:66])[NH:61]1)[O:43][CH3:44])=[O:36])[CH3:31])=[O:29])[CH:25]([CH3:26])[CH3:27])=[O:22])([CH3:84])[NH2:18]

Participants

4

Reactant 2

HCID 8082PiperidineHCID 86685776HCID 86685776, compound

Product 1

HCID 866857752-methylalanyl-N-{(3R,4S,5S)-1-[(2S)-2-{(3R,4R,7S)-7-benzyl-4-methyl-18-[(4S,5R)-5-methyl-2-oxoimidazolidin-4-yl]-5,8,13-trioxo-2-oxa-6,9,12-triazaoctadecan-3-yl}pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl}-N-methyl-L-valinamideYield 53.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Following general procedure A using #256 (5 mg, 0.004 mmol, 1.0 eq.) and piperidine (0.02 mL, 0.2 mmol, 50 eq.) in 0.7 mL of DMF followed by purification (Method J) afforded #257 (2 mg, 50%) as a colorless glass. LC-MS (Protocol Q1): m/z 1164.8 [M+H+], retention time=0.99 minutes. 1H NMR (400 MHz, DMSO-d6), δ 8.44-8.52 (m), 8.06-8.20 (m), 7.96-8.01 (m), 7.69-7.83 (m), 7.20-7.28 (m), 7.11-7.19 (m), 3.38-3.83 (m), 3.19-3.26 (m), 3.03-3.12 (m), 2.98 (s), 2.91 (s), 2.75 (s), 2.65-2.70 (m), 2.01-2.36 (m), 1.65-1.87 (m), 1.39-1.57 (m), 1.13-1.37 (m), 1.04-1.08 (m), 0.74-1.01 (m).

Workup

  1. customfollowed by purification (Method J)

Sources & evidence

ORD record
ord-ecd2a7bf904849e4a693b14ebdfa0ba8
Source dataset
uspto-grants-2014_09
Patent number
US08828401B2

Reaction notes

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