Dicyclohexylcarbodiimide → 2-[[[1-(2-Amino-4-thiazolyl)-2-[[1-[[[[3-[(3,4-dihydroxybenzoyl)amino]-2-oxo-1-imidazolidinyl]sulfonyl]amino]carbonyl]-2-oxo-3-azetidinyl]amino]-2-oxoethylidene]amino]oxy]-2-methylpropanoic acid, diphenylmethyl ester

HRID 2292326Notes

Reaction equation

HRID 2292326 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[C:5](/[C:7](=[N:11]/[O:12][C:13]([C:16]([O:18][CH:19]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:17])([CH3:15])[CH3:14])/[C:8]([OH:10])=O)[N:6]=1.ON1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1.FC(F)(F)C(O)=O.[NH2:64][C@H:65]1[CH2:68][N:67]([C:69]([NH:71][S:72]([N:75]2[CH2:79][CH2:78][N:77]([NH:80][C:81](=[O:90])[C:82]3[CH:87]=[CH:86][C:85]([OH:88])=[C:84]([OH:89])[CH:83]=3)[C:76]2=[O:91])(=[O:74])=[O:73])=[O:70])[C:66]1=[O:92]>CN(C)C=O.C(N(CC)CC)C>[NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7](=[N:11][O:12][C:13]([CH3:14])([CH3:15])[C:16]([O:18][CH:19]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[O:17])[C:8]([NH:64][CH:65]2[CH2:68][N:67]([C:69]([NH:71][S:72]([N:75]3[CH2:79][CH2:78][N:77]([NH:80][C:81](=[O:90])[C:82]4[CH:87]=[CH:86][C:85]([OH:88])=[C:84]([OH:89])[CH:83]=4)[C:76]3=[O:91])(=[O:73])=[O:74])=[O:70])[C:66]2=[O:92])=[O:10])[N:6]=1

Participants

7

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 135359672-Amino-alpha-((2-(diphenylmethoxy)-1,1-dimethyl-2-oxoethoxy)imino)thiazol-4-acetic acidHCID 131715830(S)-3-amino-N-[[3-[(3,4-dihydroxybenzoyl)amino]-2-oxo-1-imidazolidinyl]sulfonyl]-2-oxo-1-azetidinecarboxamide, trifluoroacetate salt

Product 1

HCID 867427002-[[[1-(2-Amino-4-thiazolyl)-2-[[1-[[[[3-[(3,4-dihydroxybenzoyl)amino]-2-oxo-1-imidazolidinyl]sulfonyl]amino]carbonyl]-2-oxo-3-azetidinyl]amino]-2-oxoethylidene]amino]oxy]-2-methylpropanoic acid, diphenylmethyl esterYield 105.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

(Z)-2-Amino-α-[[1-(diphenylmethoxycarbonyl)-1-methylethoxy]imino]-4-thiazoleacetic acid (0.88 g, 0.002 mol) was dissolved in 20 ml of dimethylformamide followed by 0.3 g of N-hydroxybenzotriazole (containing 13% water), followed by 0.5 g of dicyclohexylcarbodiimide and 0.28 ml of triethylamine. The mixture was stirred at room temperature for 1 hour, then 1.08 g (0.002 mol) of (S)-3-amino-N-[[3-[(3,4-dihydroxybenzoyl)amino]-2-oxo-1-imidazolidinyl]sulfonyl]-2-oxo-1-azetidinecarboxamide, trifluoroacetate salt (see Example 1D) was added. The mixture was stirred at room temperature overnight. The precipitate (dicyclohexylurea) was filtered off and the filtrate evaporated in vacuo. Trituration of the remaining syrup with ether yielded 1.8 g of the title compound in crude form.

Workup

  1. stirringThe mixture was stirred at room temperature overnight
  2. filtrationThe precipitate (dicyclohexylurea) was filtered off
  3. customthe filtrate evaporated in vacuo

Sources & evidence

ORD record
ord-af9acfd90df5480288997b151415446e
Source dataset
uspto-grants-1989_01
Patent number
US04801705

Reaction notes

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