Hydrochloric Acid → HCID 117735614, compound

HRID 1482278Notes

Reaction equation

HRID 1482278 reaction equation
ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.[CH2:23]([SH:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.[NH:31]1[C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[C:33]([CH2:40][C@@H:41]([C:78](=[O:135])[O:79][CH2:80][C:81]([N:83]2[CH2:87][CH2:86][CH2:85][C@H:84]2[C:88]([NH:90][C@@H:91]([CH2:110][CH2:111][CH2:112][CH2:113][NH:114][C:115]([C@@H:117]2[CH2:121][S:120][CH2:119][N:118]2[C:122]([O:124][CH2:125][C:126]2[CH:131]=[CH:130][C:129]([N:132]=[N+:133]=[N-:134])=[CH:128][CH:127]=2)=[O:123])=[O:116])[C:92]([NH:94][C@H:95]([C:100]([N:102]2[CH2:106][CH2:105][CH2:104][C@H:103]2[C:107](=[O:109])[NH2:108])=[O:101])[CH2:96][C:97](O)=[O:98])=[O:93])=[O:89])=[O:82])[NH:42][C:43](=[O:77])[C@H:44]([CH2:70][CH2:71][CH2:72][CH2:73][N:74]([CH3:76])[CH3:75])[NH:45][C:46](=[O:69])[C@@H:47]([NH:55][C:56]([O:58][CH2:59][C:60]2[CH:65]=[CH:64][C:63]([N:66]=[N+:67]=[N-:68])=[CH:62][CH:61]=2)=[O:57])[CH2:48][S:49][S:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[CH:32]1.Cl>CN(C)C=O>[NH:31]1[C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[C:33]([CH2:40][C@@H:41]([C:78](=[O:135])[O:79][CH2:80][C:81]([N:83]2[CH2:87][CH2:86][CH2:85][C@H:84]2[C:88]([NH:90][C@H:91]([C:92]([NH:94][C@@H:95]([CH2:96][C:97]([S:30][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:98])[C:100]([N:102]2[CH2:106][CH2:105][CH2:104][C@H:103]2[C:107](=[O:109])[NH2:108])=[O:101])=[O:93])[CH2:110][CH2:111][CH2:112][CH2:113][NH:114][C:115]([C@@H:117]2[CH2:121][S:120][CH2:119][N:118]2[C:122]([O:124][CH2:125][C:126]2[CH:127]=[CH:128][C:129]([N:132]=[N+:133]=[N-:134])=[CH:130][CH:131]=2)=[O:123])=[O:116])=[O:89])=[O:82])[NH:42][C:43](=[O:77])[C@H:44]([CH2:70][CH2:71][CH2:72][CH2:73][N:74]([CH3:76])[CH3:75])[NH:45][C:46](=[O:69])[C@@H:47]([NH:55][C:56]([O:58][CH2:59][C:60]2[CH:61]=[CH:62][C:63]([N:66]=[N+:67]=[N-:68])=[CH:64][CH:65]=2)=[O:57])[CH2:48][S:49][S:50][C:51]([CH3:52])([CH3:53])[CH3:54])=[CH:32]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 7509Benzyl mercaptanHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 117735798HCID 117735798, compound

Product 1

HCID 117735614HCID 117735614, compoundYield 85%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1-Hydroxybenzotriazole (HOBt) (13.4 mg, 0.099 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI.HCl) (19.2 mg, 0.099 mmol) and benzylmercaptane (BnSH) (19.4 μL, 0.165 mmol) were added to a solution of (S)-3-((S)-2-((S)-1-((6R,9S,12S)-12-((1H-indol-3-yl)methyl)-6-((((4-azidobenzyl)oxy) carbonyl)amino)-9-(4-(dimethylamino)butyl)-2,2-dimethyl-7,10,13-trioxo-14-oxa-3,4-dithia-8,11-diazahexadecane-16-oyl)pyrrolidine-2-carboxamido)-6-((R)-3-(((4-azidobenzyl)oxy) carbonyl) thiazolidine-4-carboxamido)hexanamido)-4-((S)-2-carbamoylpyrrolidin-1-yl)-4-oxobutanoic acid (Acbz-Cys(StBu)-Lys(Me2)-Trp-HOGly-Pro-Lys(Acbz-Thz)-Asp-Pro-NH2) (Compound SP615) (50 mg, 0.033 mmol) in Dimethylformamide (DMF) (331 μl) at room temperature under a nitrogen atmosphere, and the mixture was stirred at the same temperature for 1 hour. A 1 N aqueous hydrochloric acid solution (43 μl) was added to the reaction solution, and the mixture was purified by reverse-phase silica gel chromatography (0.1% aqueous formic acid solution/0.1% formic acid-acetonitrile solution) to afford (R)-4-azidobenzyl 4-(((S)-5-((S)-1-((6R,9S,12S)-12-((1H-indol-3-yl)methyl)-6-((((4-azidobenzyl)oxy) carbonyl)amino)-9-(4-(dimethylamino)butyl)-2,2-dimethyl-7,10,13-trioxo-14-oxa-3,4-dithia-8,11-diazahexadecan-16-oyl)pyrrolidine-2-carboxamido)-6-(((S)-4-(benzylthio)-1-((S)-2-carbamoylpyrrolidin-1-yl)-1,4-dioxobutan-2-yl)amino)-6-oxohexyl)carbamoyl)thiazolidine-3-carboxylate (Acbz-Cys(StBu)-Lys(Me2)-Trp-HOGly-Pro-Lys(Acbz-Thz)-Asp(SBn)-Pro-NH2) (Compound SP616) (45.7 mg, 85%).

Workup

  1. customthe mixture was purified by reverse-phase silica gel chromatography (0.1% aqueous formic acid solution/0.1% formic acid-acetonitrile solution)

Sources & evidence

ORD record
ord-821b215130994b30bd4ef82da1a1f93c
Source dataset
uspto-grants-2016_08
Patent number
US09409952B2

Reaction notes

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