Diisopropylcarbodiimide → Cypate Bombesin

HRID 2262451

반응식

HRID 2262451 반응식
[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]

참가 물질

5

반응물 4

HCID 12734DiisopropylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 10963571CypateHCID 16201612Bombesin

생성물 1

HCID 86612194Cypate Bombesin

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-3fd3070f575042cd8698b219af2d5783
출처 데이터셋
uspto-grants-2010_12
특허 번호
US07850946B2

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