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4-Methylmorpholine → Z-Asp(OtBu)-Leu-Lys(Boc)-Glu(OtBu)-Lys(Boc)-Lys(Boc)-Glu(OtBu)-Val-Val-Glu(OtBu)-Glu(OtBu)-Ala-Glu(OtBu)-Asn-OtBu

HRID 462874
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HRID 462874 반응식
[NH2:1][C@H:2]([C:12]([NH:14][C@H:15]([C:28]([NH:30][C@H:31]([C:44]([NH:46][C@H:47]([C:57]([NH:59][C@H:60]([C:64]([NH:66][C@H:67]([C:71]([NH:73][C@H:74]([C:84]([NH:86][C@H:87]([C:97]([NH:99][C@H:100]([C:102]([NH:104][C@H:105]([C:115]([NH:117][C@H:118]([C:123]([O:125][C:126]([CH3:129])([CH3:128])[CH3:127])=[O:124])[CH2:119][C:120](=[O:122])[NH2:121])=[O:116])[CH2:106][CH2:107][C:108](=[O:114])[O:109][C:110]([CH3:113])([CH3:112])[CH3:111])=[O:103])[CH3:101])=[O:98])[CH2:88][CH2:89][C:90](=[O:96])[O:91][C:92]([CH3:95])([CH3:94])[CH3:93])=[O:85])[CH2:75][CH2:76][C:77](=[O:83])[O:78][C:79]([CH3:82])([CH3:81])[CH3:80])=[O:72])[CH:68]([CH3:70])[CH3:69])=[O:65])[CH:61]([CH3:63])[CH3:62])=[O:58])[CH2:48][CH2:49][C:50](=[O:56])[O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:45])[CH2:32][CH2:33][CH2:34][CH2:35][NH:36][C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])=[O:29])[CH2:16][CH2:17][CH2:18][CH2:19][NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])=[O:13])[CH2:3][CH2:4][C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8].[CH2:130]([O:137][C:138]([NH:140][C@H:141]([C:150]([NH:152][C@H:153]([C:158]([NH:160][C@H:161]([C:174]([OH:176])=O)[CH2:162][CH2:163][CH2:164][CH2:165][NH:166][C:167]([O:169][C:170]([CH3:173])([CH3:172])[CH3:171])=[O:168])=[O:159])[CH2:154][CH:155]([CH3:157])[CH3:156])=[O:151])[CH:142](C(C)(C)C)[C:143](=[O:145])[OH:144])=[O:139])C1C=CC=CC=1.[CH:177]1[CH:178]=[CH:179][C:180]2N(O)N=N[C:181]=2[CH:182]=1.C1CCC(N=C=N[CH:196]2[CH2:201][CH2:200]CCC2)CC1.[CH3:202]N1CCOCC1>CC(O)=O.CO.C(Cl)(Cl)Cl.O.CS(C)=O.CN(C=O)C>[NH:140]([C:138]([O:137][CH2:130][C:181]1[CH:180]=[CH:179][CH:178]=[CH:177][CH:182]=1)=[O:139])[C@H:141]([C:150]([NH:152][C@H:153]([C:158]([NH:160][C@H:161]([C:174]([NH:1][C@H:2]([C:12]([NH:14][C@H:15]([C:28]([NH:30][C@H:31]([C:44]([NH:46][C@H:47]([C:57]([NH:59][C@H:60]([C:64]([NH:66][C@H:67]([C:71]([NH:73][C@H:74]([C:84]([NH:86][C@H:87]([C:97]([NH:99][C@H:100]([C:102]([NH:104][C@H:105]([C:115]([NH:117][C@H:118]([C:123]([O:125][C:126]([CH3:127])([CH3:128])[CH3:129])=[O:124])[CH2:119][C:120](=[O:122])[NH2:121])=[O:116])[CH2:106][CH2:107][C:108](=[O:114])[O:109][C:110]([CH3:113])([CH3:112])[CH3:111])=[O:103])[CH3:101])=[O:98])[CH2:88][CH2:89][C:90](=[O:96])[O:91][C:92]([CH3:93])([CH3:94])[CH3:95])=[O:85])[CH2:75][CH2:76][C:77](=[O:83])[O:78][C:79]([CH3:80])([CH3:81])[CH3:82])=[O:72])[CH:68]([CH3:70])[CH3:69])=[O:65])[CH:61]([CH3:63])[CH3:62])=[O:58])[CH2:48][CH2:49][C:50](=[O:56])[O:51][C:52]([CH3:53])([CH3:54])[CH3:55])=[O:45])[CH2:32][CH2:33][CH2:34][CH2:35][NH:36][C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])=[O:29])[CH2:16][CH2:17][CH2:18][CH2:19][NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])=[O:13])[CH2:3][CH2:4][C:5](=[O:11])[O:6][C:7]([CH3:8])([CH3:9])[CH3:10])=[O:176])[CH2:162][CH2:163][CH2:164][CH2:165][NH:166][C:167]([O:169][C:170]([CH3:171])([CH3:172])[CH3:173])=[O:168])=[O:159])[CH2:154][CH:155]([CH3:157])[CH3:156])=[O:151])[CH2:142][C:143](=[O:145])[O:144][C:201]([CH3:200])([CH3:196])[CH3:202]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

12

반응물 5

HCID 79724-MethylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 13501922H-Glu(OtBu)-Lys(Boc)-Lys(Boc)-Glu(OtBu)-Val-Val-Glu(OtBu)-Glu(OtBu)-Ala-Glu(OtBu)-Asn-OtBuHCID 131714165N-Benzyloxycarbonyl-beta-tert-butyl-L-aspartyl-L-leucyl-Nepsilon-tert-butyloxycarbonyl-L-lysine

생성물 1

HCID 16162891Z-Asp(OtBu)-Leu-Lys(Boc)-Glu(OtBu)-Lys(Boc)-Lys(Boc)-Glu(OtBu)-Val-Val-Glu(OtBu)-Glu(OtBu)-Ala-Glu(OtBu)-Asn-OtBu

시약·촉매·용매 6

HCID 176Acetic Acid용매2회HCID 679Dimethyl Sulfoxide용매HCID 887Methanol용매2회HCID 962Water용매HCID 6212Chloroform용매2회HCID 6228Dimethylformamide용매

실험 절차

The DMF:DMSO-containing solution of H-Glu(OtBu)-Lys(Boc)-Lys(Boc)-Glu(OtBu)-Val-Val-Glu(OtBu)-Glu(OtBu)-Ala-Glu(OtBu)-Asn-OtBu (~23 mmol) from step (d) was combined with Z-Asp(OtBu)-Leu-Lys(Boc)-OH (IV, 18.6 g, 28.0 mmol, 1.2 eq.) and HOBt (10.62 g, 69.0 mmol, 3.0 eq.) added and the solution cooled to 0°. DCC (7.87 g, 38.0 mmol, 1.65 eq.) was added to the cold stirring (mechanical) reaction mixture and the pH was maintained at 7.5-8.0 by addition of N-methylmorpholine (~17 mL). Stirring proceeded for 1 h at 0° and 23 h at 25°. The resultant reaction mixture was poured into H2O (10 L) and stirred for 1.5 h. The product was collected by filtration, washed with H2O (5 L), dried and washed with MeOH using the centrifuge to separate the 2 layers. When all the dicyclohexylurea was removed the product was pooled and dried in vacuo to give 44.56 g (77.9%); mp >330°; [α] D25 -11.56° (c 1, TFE); Rf 0.16 (CHCl3 :MeOH:AcOH; 80-5-1); Rf 0.36 (CHCl3 :MeOH:TFE:AcOH; 85-10-2.5-1).

후처리

  1. additionadded
  2. temperaturethe solution cooled to 0°
  3. custom(mechanical) reaction mixture
  4. stirringStirring
  5. customThe resultant reaction mixture
  6. stirringstirred for 1.5 h
  7. filtrationThe product was collected by filtration
  8. washwashed with H2O (5 L)
  9. customdried
  10. washwashed with MeOH using the centrifuge
  11. customto separate the 2 layers
  12. customWhen all the dicyclohexylurea was removed the product
  13. customdried in vacuo
  14. customto give 44.56 g (77.9%)

출처 및 근거

ORD 기록
ord-3de57346c34146479c4336a663dc9ce7
출처 데이터셋
uspto-grants-1985_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US04517119

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