Dicyclohexylcarbodiimide → HCID 178455946, compound

HRID 65374Notes

Reaction equation

HRID 65374 reaction equation
[NH:1](C(OCC1C=CC=CC=1)=O)[C@H:2]([C:7]([NH:9][C@H:10]([C:14](N[C@H](C(N[C@H](C(N[C@H](C(OC)=O)CCCCNC(OC(C)(C)C)=O)=O)CC1N=CNC=1)=O)[C@H](CC)C)=[O:15])[CH:11]([CH3:13])[CH3:12])=[O:8])[CH2:3][CH:4]([CH3:6])[CH3:5].[NH:62]([C:78]([O:80][CH2:81][C:82]1[CH:87]=[CH:86][CH:85]=[CH:84][CH:83]=1)=[O:79])[C@H:63]([C:68]([NH:70][C@H:71]([C:75]([OH:77])=O)[CH:72]([CH3:74])C)=[O:69])[CH2:64][CH:65]([CH3:67])[CH3:66].[NH2:88][C@H:89]([C:94]([NH:96][C@H:97]([C:104]([NH:106][C@H:107]([C:120]([O:122][CH3:123])=[O:121])[CH2:108][CH2:109][CH2:110][CH2:111][NH:112][C:113]([O:115][C:116]([CH3:119])([CH3:118])[CH3:117])=[O:114])=[O:105])[CH2:98][C:99]1[N:103]=[CH:102][NH:101][CH:100]=1)=[O:95])[C@H:90]([CH2:92][CH3:93])[CH3:91].C1C=[CH:126][C:127]2N(O)N=N[C:128]=2C=1.C1CC[CH:137]([N:140]=[C:141]=[N:142]C2CCCCC2)CC1>CN(C=O)C>[NH:62]([C:78]([O:80][CH2:81][C:82]1[CH:83]=[CH:84][CH:85]=[CH:86][CH:87]=1)=[O:79])[C@H:63]([C:68]([NH:70][C@H:71]([C:75]([NH:1][C@H:2]([C:7]([NH:9][C@H:10]([C:14]([NH:88][C@H:89]([C:94]([NH:96][C@H:97]([C:104]([NH:106][C@H:107]([C:120]([O:122][CH3:123])=[O:121])[CH2:108][CH2:109][CH2:110][CH2:111][NH:112][C:113]([O:115][C:116]([CH3:117])([CH3:118])[CH3:119])=[O:114])=[O:105])[CH2:98][C:99]1[N:103]=[CH:102][NH:101][CH:100]=1)=[O:95])[C@H:90]([CH2:92][CH3:93])[CH3:91])=[O:15])[CH:11]([CH3:13])[CH3:12])=[O:8])[CH2:3][CH:4]([CH3:6])[CH3:5])=[O:77])[CH2:72][C:74]1[N:142]=[CH:141][NH:140][CH:137]=1)=[O:69])[CH2:64][C:65]1[CH:66]=[CH:126][CH:127]=[CH:128][CH:67]=1

Participants

7

Reactant 5

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 14488993N-[(Phenylmethoxy)carbonyl]-L-leucyl-L-valineHCID 178455957HCID 178455957, compoundHCID 178455961HCID 178455961, compound

Product 1

HCID 178455946HCID 178455946, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Z-Leu-Val-Ile-His-Lys(BOC)-OMe: 300 mg of Z-Leu-Val-OH, 454 mg of H-Ile-His-Lys(BOC)-OMe (manufactured as discribed in European Patent Applicaiton No. 111 266) and 136 mg of HOBt are dissolved in 5 ml of DMF, cooled to 0° and 198 mg of DCCI are added. After stirring briefly, the whole is left to stand overnight at 0° and for a further 24 hours at room temperature and then the DCH which has crystallised out is filtered off. The filtrate is concentrated in a high vacuum at 40° and the oily residue is dissolved in 12 ml of methanol/glacial acetic acid/H20 (94:3:3) and heated for 1 hour at 60°. The solution is again concentrated to dryness and the residue is purified by Craig distribution in the system methanol/acetate buffer/ethylene chloride/chloroform 10:3:8:4 (acetate buffer: 14.3 ml of glacial acetic acid and 9.6 g of ammonium acetate in 1000 ml of water) over 800 stages. The fractions pure according to thin layer chromatography (K=0.26) are combined, concentrated to dryness, pulverised and subsequently dried in a high vacuum at 40°. Rf (B17)=0.70, Rf (S4)=0.75.

Workup

  1. temperaturecooled to 0°
  2. waitthe whole is left
  3. customthe DCH which has crystallised out
  4. filtrationis filtered off
  5. concentrationThe filtrate is concentrated in a high vacuum at 40°
  6. dissolutionthe oily residue is dissolved in 12 ml of methanol/glacial acetic acid/H20 (94:3:3)
  7. temperatureheated for 1 hour at 60°
  8. concentrationThe solution is again concentrated to dryness
  9. customthe residue is purified by Craig distribution in the system methanol/acetate buffer/ethylene chloride/chloroform 10:3:8:4 (acetate buffer: 14.3 ml of glacial acetic acid and 9.6 g of ammonium acetate in 1000 ml of water) over 800 stages
  10. concentrationconcentrated to dryness
  11. customsubsequently dried in a high vacuum at 40°

Sources & evidence

ORD record
ord-1dc1bbfc55d2412b95ccb52dc3e5dd47
Source dataset
uspto-grants-1986_09
Patent number
US04613676

Reaction notes

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