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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
ノート
印刷プレビュー

反応式

HRID 462874 の反応式
[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]
参加物実験手順後処理出典と根拠反応ノート

参加物

12

反応物 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

生成物 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

試薬・触媒・溶媒 6

HCID 176Acetic Acid溶媒2 回HCID 679Dimethyl Sulfoxide溶媒HCID 887Methanol溶媒2 回HCID 962Water溶媒HCID 6212Chloroform溶媒2 回HCID 6228Dimethylformamide溶媒

実験手順

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).

後処理

  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%)

出典と根拠

ORDレコード
ord-3de57346c34146479c4336a663dc9ce7
出典データセット
uspto-grants-1985_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US04517119

反応ノート

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