Dimethylformamide → HCID 131713852, compound

HRID 1632400Notes

Reaction equation

HRID 1632400 reaction equation
[NH2:1][C@H:2]([C:6]([NH:8][C@H:9]([C:16]([NH:18][C@H:19]([C:22]([NH:24][C@H:25]([C:30]([NH:32][CH2:33][C:34]([NH:36][C@H:37]([C:42]([NH:44][C@H:45]([C:53]([NH:55][C@H:56]([C:64]([NH:66][C@H:67]([C:69]([NH:71][C@H:72]([C:77]([NH:79][C@H:80]([C:85]([NH:87][C@H:88]([C:93]([NH:95][C@H:96]([C:101]([NH:103][C@H:104]([C:106]([NH:108][C@H:109]([C:115]([OH:117])=[O:116])[CH2:110][CH2:111][C:112](=[O:114])[NH2:113])=[O:107])[CH3:105])=[O:102])[CH2:97][CH:98]([CH3:100])[CH3:99])=[O:94])[CH2:89][CH:90]([CH3:92])[CH3:91])=[O:86])[C@H:81]([CH2:83][CH3:84])[CH3:82])=[O:78])[CH2:73][CH:74]([CH3:76])[CH3:75])=[O:70])[CH3:68])=[O:65])[CH2:57][CH2:58][CH2:59][NH:60][C:61](=[NH:63])[NH2:62])=[O:54])[CH2:46][CH2:47][CH2:48][NH:49][C:50](=[NH:52])[NH2:51])=[O:43])[CH2:38][C:39](=[O:41])[NH2:40])=[O:35])=[O:31])[CH2:26][CH:27]([CH3:29])[CH3:28])=[O:23])[CH2:20][OH:21])=[O:17])[CH2:10][C:11]1[N:15]=[CH:14][NH:13][CH:12]=1)=[O:7])[C@@H:3]([CH3:5])[OH:4].CN(C)C=O.[N-]=[N+]=[N-].[NH:126](C(OCC1C=CC=CC=1)=O)[C@H:127]([C:130]([NH:132][C@H:133]([C:138]([NH:140][C@H:141]([C:146]([N:148]1[CH2:172][CH2:171][CH2:170][C@H:149]1[C:150]([NH:152][C@H:153]([C:159](NNC(OC(C)(C)C)=O)=[O:160])[CH2:154][CH2:155][C:156](=[O:158])[NH2:157])=[O:151])=[O:147])[CH2:142][CH:143]([CH3:145])[CH3:144])=[O:139])[CH2:134][C:135](=[O:137])[OH:136])=[O:131])[CH2:128][OH:129]>CN(C)P(=O)(N(C)C)N(C)C>[NH2:126][C@H:127]([C:130]([NH:132][C@H:133]([C:138]([NH:140][C@H:141]([C:146]([N:148]1[CH2:172][CH2:171][CH2:170][C@H:149]1[C:150]([NH:152][C@H:153]([C:159]([NH:1][C@H:2]([C:6]([NH:8][C@H:9]([C:16]([NH:18][C@H:19]([C:22]([NH:24][C@H:25]([C:30]([NH:32][CH2:33][C:34]([NH:36][C@H:37]([C:42]([NH:44][C@H:45]([C:53]([NH:55][C@H:56]([C:64]([NH:66][C@H:67]([C:69]([NH:71][C@H:72]([C:77]([NH:79][C@H:80]([C:85]([NH:87][C@H:88]([C:93]([NH:95][C@H:96]([C:101]([NH:103][C@H:104]([C:106]([NH:108][C@H:109]([C:115]([OH:117])=[O:116])[CH2:110][CH2:111][C:112](=[O:114])[NH2:113])=[O:107])[CH3:105])=[O:102])[CH2:97][CH:98]([CH3:99])[CH3:100])=[O:94])[CH2:89][CH:90]([CH3:91])[CH3:92])=[O:86])[C@H:81]([CH2:83][CH3:84])[CH3:82])=[O:78])[CH2:73][CH:74]([CH3:75])[CH3:76])=[O:70])[CH3:68])=[O:65])[CH2:57][CH2:58][CH2:59][NH:60][C:61](=[NH:62])[NH2:63])=[O:54])[CH2:46][CH2:47][CH2:48][NH:49][C:50](=[NH:51])[NH2:52])=[O:43])[CH2:38][C:39](=[O:41])[NH2:40])=[O:35])=[O:31])[CH2:26][CH:27]([CH3:28])[CH3:29])=[O:23])[CH2:20][OH:21])=[O:17])[CH2:10][C:11]1[N:15]=[CH:14][NH:13][CH:12]=1)=[O:7])[C@@H:3]([CH3:5])[OH:4])=[O:160])[CH2:154][CH2:155][C:156](=[O:158])[NH2:157])=[O:151])=[O:147])[CH2:142][CH:143]([CH3:145])[CH3:144])=[O:139])[CH2:134][C:135](=[O:136])[OH:137])=[O:131])[CH2:128][OH:129]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 33558AzideHCID 15585619HCID 15585619, compoundHCID 178455911HCID 178455911, compound

Product 1

HCID 131713852HCID 131713852, compound

Reagents, catalysts & solvents 1

HCID 12679HexamethylphosphoramideSolvent

Conditions

Temperature
4 °C

Procedure

This reaction mixture was added to a mixture consisting of 80 mg of Peptide B, i.e., H-Thr-His-Ser-Leu-Gly-Asn-Arg-Arg-Ala-Leu-Ile-Leu-Leu-Ala-Gln-OH, 5 ml of dimethylformamide and 6 ml of hexamethylphosphoric triamide, and stirred at 4° C. for 20 hours. Further, to the reaction mixture was added 116 mg of azide product of Z-Ser-Asp-Leu-Pro-Gln-NHNHBoc, then stirred for 28 hours. Dimethylformamide was removed by distillation and the residue thus obtained was extracted with butanol. The extract was washed with water and butanol was removed by distillation. Then the residue was crystallized from petroleum ether and the crystals precipitated were collected by filtration, then reprecipitated from methanol-ethyl acetate. Thus obtained Z-Ser-Asp-Leu-Pro-Gln-Thr-His-Ser-Leu-Gly-Asn-Arg-Arg-Ala-Leu-Ile-Leu-Leu-Ala-Gln-OH was dissolved in 30 ml of methanol with 30 ml of 10%-acetic acid and was catalytically reduced by using palladium as the catalyst. The catalyst was removed by filtration and the solvent was also removed by distillation. The residue thus obtained was purified by using Sephdex G-25 followed by LH-20 (eluting solvent: 1/1000N-hydrochloric acid was used respectively) to obtain 58 mg of H-Ser-Asp-Leu-Pro-Gln-Thr-His-Ser-Leu-Gly-Asn-Arg-Arg-Ala-Leu-Ile-Leu-Leu-Ala-Gln-OH. Hereinafter, this product is referred to as [Peptide C].

Workup

  1. additionThis reaction mixture was added to a mixture
  2. stirringstirred for 28 hours
  3. customDimethylformamide was removed by distillation
  4. customthe residue thus obtained
  5. extractionwas extracted with butanol
  6. washThe extract was washed with water and butanol
  7. customwas removed by distillation
  8. customThen the residue was crystallized from petroleum ether
  9. customthe crystals precipitated
  10. filtrationwere collected by filtration
  11. customreprecipitated from methanol-ethyl acetate
  12. dissolutionThus obtained Z-Ser-Asp-Leu-Pro-Gln-Thr-His-Ser-Leu-Gly-Asn-Arg-Arg-Ala-Leu-Ile-Leu-Leu-Ala-Gln-OH was dissolved in 30 ml of methanol with 30 ml of 10%-acetic acid
  13. customThe catalyst was removed by filtration
  14. customthe solvent was also removed by distillation
  15. customThe residue thus obtained
  16. customwas purified
  17. washeluting solvent

Sources & evidence

ORD record
ord-5f6e650d8cf04d4aa8658c28d4198ead
Source dataset
uspto-grants-1984_10
Patent number
US04474754

Reaction notes

Loading…