Diisopropylcarbodiimide → Cypate Bombesin

HRID 2262451

Reaktionsgleichung

Reaktionsgleichung von HRID 2262451
[CH3:1][C@H:2]([NH:43][C:44]([C@@H:46]([NH:57][C:58]([C@@H:60]([NH:66][C:67]([C@@H:69]([NH:74][C:75]([CH2:77][NH:78][C:79]([C@@H:81]([NH:86][C:87]([C@@H:89]([NH:97][C:98]([C@@H:100]([NH:106][C:107]([C@H:109]1[NH:114][C:112](=[O:113])[CH2:111][CH2:110]1)=[O:108])[CH2:101][CH2:102][C:103]([NH2:105])=[O:104])=[O:99])[CH2:90][CH2:91][CH2:92][NH:93][C:94]([NH2:96])=[NH:95])=[O:88])[CH2:82][CH:83]([CH3:85])[CH3:84])=[O:80])=[O:76])[CH2:70][C:71]([NH2:73])=[O:72])=[O:68])[CH2:61][CH2:62][C:63]([NH2:65])=[O:64])=[O:59])[CH2:47][C:48]1[C:52]2[CH:53]=[CH:54][CH:55]=[CH:56][C:51]=2[NH:50][CH:49]=1)=[O:45])[C:3]([NH:5][C@H:6]([C:10]([NH:12][CH2:13][C:14]([NH:16][C@H:17]([C:24]([NH:26][C@H:27]([C:32]([NH:34][C@H:35]([C:40]([NH2:42])=[O:41])[CH2:36][CH2:37][S:38][CH3:39])=[O:33])[CH2:28][CH:29]([CH3:31])[CH3:30])=[O:25])[CH2:18][C:19]1[NH:23][CH:22]=[N:21][CH:20]=1)=[O:15])=[O:11])[CH:7]([CH3:9])[CH3:8])=[O:4].[CH3:115][C:116]1([CH3:161])[C:128](/[CH:129]=[CH:130]/[CH:131]=[CH:132]/[CH:133]=[CH:134]/[CH:135]=[C:136]2\[C:137]([CH3:155])([CH3:154])[C:138]3[C:139]4[CH:140]=[CH:141][CH:142]=[CH:143][C:144]=4[CH:145]=[CH:146][C:147]=3[N:148]\2[CH2:149][CH2:150][C:151]([OH:153])=[O:152])=[N+:127]([CH2:156][CH2:157][C:158]([OH:160])=[O:159])[C:126]2[CH:125]=[CH:124][C:123]3[CH:122]=[CH:121][CH:120]=[CH:119][C:118]=3[C:117]1=2.[Br-:162].C1C=CC2N(O)N=NC=2C=1.CC(C)N=C=NC(C)C>>[CH3:115][C:116]1([CH3:161])[C:128](/[CH:129]=[CH:130]/[CH:131]=[CH:132]/[CH:133]=[CH:134]/[CH:135]=[C:136]2\[C:137]([CH3:154])([CH3:155])[C:138]3[C:139]4[CH:140]=[CH:141][CH:142]=[CH:143][C:144]=4[CH:145]=[CH:146][C:147]=3[N:148]\2[CH2:149][CH2:150][C:151]([OH:153])=[O:152])=[N+:127]([CH2:156][CH2:157][C:158]([OH:160])=[O:159])[C:126]2[CH:125]=[CH:124][C:123]3[CH:122]=[CH:121][CH:120]=[CH:119][C:118]=3[C:117]1=2.[Br-:162].[CH3:1][C@H:2]([NH:43][C:44]([C@@H:46]([NH:57][C:58]([C@@H:60]([NH:66][C:67]([C@@H:69]([NH:74][C:75]([CH2:77][NH:78][C:79]([C@@H:81]([NH:86][C:87]([C@@H:89]([NH:97][C:98]([C@@H:100]([NH:106][C:107]([C@H:109]1[NH:114][C:112](=[O:113])[CH2:111][CH2:110]1)=[O:108])[CH2:101][CH2:102][C:103]([NH2:105])=[O:104])=[O:99])[CH2:90][CH2:91][CH2:92][NH:93][C:94]([NH2:96])=[NH:95])=[O:88])[CH2:82][CH:83]([CH3:84])[CH3:85])=[O:80])=[O:76])[CH2:70][C:71]([NH2:73])=[O:72])=[O:68])[CH2:61][CH2:62][C:63]([NH2:65])=[O:64])=[O:59])[CH2:47][C:48]1[C:52]2[CH:53]=[CH:54][CH:55]=[CH:56][C:51]=2[NH:50][CH:49]=1)=[O:45])[C:3]([NH:5][C@H:6]([C:10]([NH:12][CH2:13][C:14]([NH:16][C@H:17]([C:24]([NH:26][C@H:27]([C:32]([NH:34][C@H:35]([C:40]([NH2:42])=[O:41])[CH2:36][CH2:37][S:38][CH3:39])=[O:33])[CH2:28][CH:29]([CH3:30])[CH3:31])=[O:25])[CH2:18][C:19]1[NH:23][CH:22]=[N:21][CH:20]=1)=[O:15])=[O:11])[CH:7]([CH3:8])[CH3:9])=[O:4]

Komponenten

5

Edukt 4

HCID 12734DiisopropylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 10963571CypateHCID 16201612Bombesin

Produkt 1

HCID 86612194Cypate Bombesin

Versuchsvorschrift

The resin-bound bombesin analog, i.e. Fmoc-Gln(Trt)-Trp(Boc)-Val-Ala-Gly-His(Trt)-Leu-Met-Lys(Boc)-Rink-Amide (SEQ ID NO: 1)resin was assembled from Rink amide-resin (50 mg, 0.031 mmol) based on the conventional Fmoc chemistry. (Peptides shown above are disclosed as SEQ ID NOS 1 and 2 respectively). After the N-terminal Fmoc was removed by piperidine in DMF (20%), a solution of Cypate (211.5 mg, 0.3 mmol), HOBT (40.5 mg, 0.30 mmol), DIC (126.0 mg, 0.1 mmol) was added. The resulting mixture was swirled overnight at room temperature. The resin was washed with DMF and DCM, cleaved with a TFA solution s (TFA:Phenol:thioanisole:water v:v 85:5:5:5, 4 ml) (2 h), and concentrated. The product was precipitated in cooled tert-butyl methyl ether to afford 2.8 mg of the crude intermediate 16.

Aufarbeitung

  1. customAfter the N-terminal Fmoc was removed by piperidine in DMF (20%)
  2. washThe resin was washed with DMF and DCM
  3. customcleaved with a TFA solution s (TFA:Phenol:thioanisole:water v:v 85:5:5:5, 4 ml) (2 h)
  4. concentrationconcentrated
  5. customThe product was precipitated in cooled tert-butyl methyl ether

Quellen und Nachweise

ORD-Eintrag
ord-3fd3070f575042cd8698b219af2d5783
Quelldatensatz
uspto-grants-2010_12
Patentnummer
US07850946B2

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