HCID 131736682, compound → HCID 131736681, compound

HRID 1482159Notes

Reaction equation

HRID 1482159 reaction equation
[NH:1](C(OCC1C=CC=CC=1)=O)[C@H:2]([C:10]([NH:12][C@H:13]([C:24]([N:26]1[CH2:120][CH2:119][CH2:118][C@H:27]1[C:28]([NH:30][C@H:31]([C:42]([NH:44][C@H:45]([C:56]([N:58]1[CH2:117][CH2:116][CH2:115][C@H:59]1[C:60]([NH:62][C@H:63]([C:74]([NH:76][C@H:77]([C:85]([NH:87][C@H:88]([C:96]([NH:98][C@H:99]([C:112]([NH2:114])=[O:113])[CH2:100][CH2:101][CH2:102][CH2:103][NH:104][C:105]([O:107][C:108]([CH3:111])([CH3:110])[CH3:109])=[O:106])=[O:97])[CH2:89][CH2:90][CH2:91][NH:92][C:93](=[NH:95])[NH2:94])=[O:86])[CH2:78][CH2:79][CH2:80][NH:81][C:82](=[NH:84])[NH2:83])=[O:75])[CH2:64][C:65]1[C:73]2[C:68](=[CH:69][CH:70]=[CH:71][CH:72]=2)[NH:67][CH:66]=1)=[O:61])=[O:57])[CH2:46][C:47]1[C:55]2[C:50](=[CH:51][CH:52]=[CH:53][CH:54]=2)[NH:49][CH:48]=1)=[O:43])[CH2:32][C:33]1[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[NH:35][CH:34]=1)=[O:29])=[O:25])[CH2:14][C:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[NH:17][CH:16]=1)=[O:11])[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[NH:9])[NH2:8]>CO>[NH2:1][C@H:2]([C:10]([NH:12][C@H:13]([C:24]([N:26]1[CH2:120][CH2:119][CH2:118][C@H:27]1[C:28]([NH:30][C@H:31]([C:42]([NH:44][C@H:45]([C:56]([N:58]1[CH2:117][CH2:116][CH2:115][C@H:59]1[C:60]([NH:62][C@H:63]([C:74]([NH:76][C@H:77]([C:85]([NH:87][C@H:88]([C:96]([NH:98][C@H:99]([C:112]([NH2:114])=[O:113])[CH2:100][CH2:101][CH2:102][CH2:103][NH:104][C:105]([O:107][C:108]([CH3:111])([CH3:110])[CH3:109])=[O:106])=[O:97])[CH2:89][CH2:90][CH2:91][NH:92][C:93](=[NH:94])[NH2:95])=[O:86])[CH2:78][CH2:79][CH2:80][NH:81][C:82](=[NH:83])[NH2:84])=[O:75])[CH2:64][C:65]1[C:73]2[C:68](=[CH:69][CH:70]=[CH:71][CH:72]=2)[NH:67][CH:66]=1)=[O:61])=[O:57])[CH2:46][C:47]1[C:55]2[C:50](=[CH:51][CH:52]=[CH:53][CH:54]=2)[NH:49][CH:48]=1)=[O:43])[CH2:32][C:33]1[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[NH:35][CH:34]=1)=[O:29])=[O:25])[CH2:14][C:15]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[NH:17][CH:16]=1)=[O:11])[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[NH:8])[NH2:9]

Participants

3

Reactant 1

HCID 131736682HCID 131736682, compound

Product 1

HCID 131736681HCID 131736681, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

A methanol solution of 1.00 equivalent of 3TPB.Z-Arg-Trp-Pro-TrpTrp-Pro-Trp-Arg-Arg-Lys(Boc)-NH2 (Mw=1787.1; purity=57.0%;) was passed several times through a column containing a methanol washed resin IRA 958 (Mw=1000, 9.00 equivalents). After the exchange had been checked by HPLC, the resin was filtered and washed three times with methanol. The combined organic phases were partially concentrated in vacuo. The concentrated solution was then diluted with water and Pd catalyst was added. The suspension was then hydrogenated for at least 6 hours at 35±5° C. The catalyst was filtered off, washed three times with a mixture methanol/water. The combined filtrates were evaporated in vacuo, the residue suspended in DMA and further concentrated in order to eliminate the remaining water. After checking the water content, the solution was titrated by HCl (0.1N) or NMR and further used without any purification.

Workup

  1. filtrationthe resin was filtered
  2. washwashed three times with methanol
  3. concentrationThe combined organic phases were partially concentrated in vacuo
  4. additionThe concentrated solution was then diluted with water and Pd catalyst
  5. additionwas added
  6. waithydrogenated for at least 6 hours at 35±5° C
  7. filtrationThe catalyst was filtered off
  8. washwashed three times with a mixture methanol/water
  9. customThe combined filtrates were evaporated in vacuo
  10. concentrationfurther concentrated in order
  11. customfurther used without any purification

Sources & evidence

ORD record
ord-10d7e5b8137e428389dbf76f33678586
Source dataset
uspto-grants-2016_08
Patent number
US09409946B2

Reaction notes

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