Diisopropylethylamine → N-(4-{2-[6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanoyl]hydrazino}-4-oxobutyl)-N-methyl-L-valyl-N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-{[(1S,2R)-2-phenyl-1-(propylcarbamoyl)cyclopropyl]amino}propyl]pyrrolidin-1-yl}-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide

HRID 882630Notes

Reaction equation

HRID 882630 reaction equation
[C:1]([CH2:4][CH2:5][CH2:6][N:7]([CH3:62])[C@H:8]([C:12]([NH:14][C@H:15]([C:19]([N:21]([C@@H:23]([C@@H:58]([CH3:61])[CH2:59][CH3:60])[C@H:24]([O:56][CH3:57])[CH2:25][C:26]([N:28]1[CH2:32][CH2:31][CH2:30][C@H:29]1[C@H:33]([O:54][CH3:55])[C@@H:34]([CH3:53])[C:35](=[O:52])[NH:36][C@@:37]1([C:46](=[O:51])[NH:47][CH2:48][CH2:49][CH3:50])[CH2:39][C@@H:38]1[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)=[O:27])[CH3:22])=[O:20])[CH:16]([CH3:18])[CH3:17])=[O:13])[CH:9]([CH3:11])[CH3:10])([OH:3])=O.Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[O:95]=[C:96]1[CH:100]=[CH:99][C:98](=[O:101])[N:97]1[CH2:102][CH2:103][CH2:104][CH2:105][CH2:106][C:107]([NH:109][NH2:110])=[O:108]>CN(C=O)C>[O:101]=[C:98]1[CH:99]=[CH:100][C:96](=[O:95])[N:97]1[CH2:102][CH2:103][CH2:104][CH2:105][CH2:106][C:107]([NH:109][NH:110][C:1](=[O:3])[CH2:4][CH2:5][CH2:6][N:7]([CH3:62])[C@H:8]([C:12]([NH:14][C@H:15]([C:19]([N:21]([C@@H:23]([C@@H:58]([CH3:61])[CH2:59][CH3:60])[C@H:24]([O:56][CH3:57])[CH2:25][C:26]([N:28]1[CH2:32][CH2:31][CH2:30][C@H:29]1[C@H:33]([O:54][CH3:55])[C@@H:34]([CH3:53])[C:35](=[O:52])[NH:36][C@@:37]1([C:46](=[O:51])[NH:47][CH2:48][CH2:49][CH3:50])[CH2:39][C@@H:38]1[C:40]1[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=1)=[O:27])[CH3:22])=[O:20])[CH:16]([CH3:18])[CH3:17])=[O:13])[CH:9]([CH3:11])[CH3:10])=[O:108]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 41703546-(2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanehydrazideHCID 56952298N-(3-carboxypropyl)-N-methyl-L-valyl-N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-{[(1S,2R)-2-phenyl-1-(propylcarbamoyl)cyclopropyl]amino)propyl]pyrrolidin-1-yl}-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide

Product 1

HCID 86718282N-(4-{2-[6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanoyl]hydrazino}-4-oxobutyl)-N-methyl-L-valyl-N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-{[(1S,2R)-2-phenyl-1-(propylcarbamoyl)cyclopropyl]amino}propyl]pyrrolidin-1-yl}-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

7.9 mg (9 μmol) of N-(3-carboxypropyl)-N-methyl-L-valyl-N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-{[(1S,2R)-2-phenyl-1-(propylcarbamoyl)cyclopropyl]amino}propyl]pyrrolidin-1-yl}-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide were dissolved in 3 ml of DMF and then admixed with 10.4 mg (54 μmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 8.3 mg (54 μmol) of 1-hydroxy-1H-benzotriazole hydrate, 9 μl of N,N-diisopropylethylamine and with 9.5 mg (36 μmol) of commercially available 6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanehydrazide. The mixture was stirred at RT overnight and then concentrated under high vacuum. The remaining residue was purified by means of preparative HPLC. Thus, 4.3 mg (22% of theory) of the title compound were obtained as a colourless foam.

Workup

  1. concentrationconcentrated under high vacuum
  2. customThe remaining residue was purified by means of preparative HPLC

Sources & evidence

ORD record
ord-73d7860d1aed42fabcba2214af16f79c
Source dataset
uspto-grants-2015_03
Patent number
US08992932B2

Reaction notes

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