Hydrochloric Acid → HCID 131709995, compound

HRID 971568Notes

Reaction equation

HRID 971568 reaction equation
[NH:1]([C:69]([O:71][CH2:72][C:73]1[CH:78]=[CH:77][CH:76]=[CH:75][CH:74]=1)=[O:70])[C@H:2]([C:10]([NH:12][C@H:13]([C:26]([NH:28][C@H:29]([C:37]([NH:39][C@H:40]([C:46]([NH:48][C@H:49]([C:54]([NH:56][C@H:57]([C:65]([NH:67]N)=[O:66])[CH2:58][C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1)=[O:55])[CH2:50][C:51](=[O:53])[NH2:52])=[O:47])[CH2:41][CH2:42][C:43](=[O:45])[NH2:44])=[O:38])[C@@H:30]([CH3:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:27])[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[CH:17][CH:16]=1)=[O:11])[C@@H:3]([CH3:9])[O:4][C:5]([CH3:8])([CH3:7])[CH3:6].Cl.C(ON=O)(C)(C)C.C(N(CC)C(C)C)(C)C.N[C@H:97]([C:102]([NH:104][C@H:105]([C:118]([NH:120][C@H:121]([C:129]([NH:131][C@H:132]([C:139]([NH:141][C@H:142]([C:150]([NH:152][C@H:153]([C:161]([N:163]1[CH2:207][CH2:206][CH2:205][C@H:164]1[C:165]([NH:167][C@H:168]([C:174]([NH:176][C@H:177]([C:185]([NH:187][C@H:188]([C:190]([NH:192][C@H:193]([C:198]([NH:200][CH2:201][C:202]([OH:204])=[O:203])=[O:199])[C@H:194]([CH2:196][CH3:197])[CH3:195])=[O:191])[CH3:189])=[O:186])[C@@H:178]([CH3:184])[O:179][C:180]([CH3:183])([CH3:182])[CH3:181])=[O:175])[CH2:169][CH2:170][C:171](=[O:173])[NH2:172])=[O:166])=[O:162])[CH2:154][C:155]1[CH:160]=[CH:159][CH:158]=[CH:157][CH:156]=1)=[O:151])[C@@H:143]([CH3:149])[O:144][C:145]([CH3:148])([CH3:147])[CH3:146])=[O:140])[CH2:133][C:134]1[N:138]=[CH:137][NH:136][CH:135]=1)=[O:130])[CH2:122][C:123]1[CH:128]=[CH:127][CH:126]=[CH:125][CH:124]=1)=[O:119])[CH2:106][CH2:107][CH2:108][CH2:109][NH:110][C:111]([O:113][C:114]([CH3:117])([CH3:116])[CH3:115])=[O:112])=[O:103])[CH2:98][C:99](=[O:101])[NH2:100]>CN(C)C=O.O1CCOCC1.CCOCC>[NH:1]([C:69]([O:71][CH2:72][C:73]1[CH:78]=[CH:77][CH:76]=[CH:75][CH:74]=1)=[O:70])[C@H:2]([C:10]([NH:12][C@H:13]([C:26]([NH:28][C@H:29]([C:37]([NH:39][C@H:40]([C:46]([NH:48][C@H:49]([C:54]([NH:56][C@H:57]([C:65]([NH:67][C@H:97]([C:102]([NH:104][C@H:105]([C:118]([NH:120][C@H:121]([C:129]([NH:131][C@H:132]([C:139]([NH:141][C@H:142]([C:150]([NH:152][C@H:153]([C:161]([N:163]1[CH2:207][CH2:206][CH2:205][C@H:164]1[C:165]([NH:167][C@H:168]([C:174]([NH:176][C@H:177]([C:185]([NH:187][C@H:188]([C:190]([NH:192][C@H:193]([C:198]([NH:200][CH2:201][C:202]([OH:204])=[O:203])=[O:199])[C@H:194]([CH2:196][CH3:197])[CH3:195])=[O:191])[CH3:189])=[O:186])[C@@H:178]([CH3:184])[O:179][C:180]([CH3:183])([CH3:182])[CH3:181])=[O:175])[CH2:169][CH2:170][C:171](=[O:173])[NH2:172])=[O:166])=[O:162])[CH2:154][C:155]1[CH:156]=[CH:157][CH:158]=[CH:159][CH:160]=1)=[O:151])[C@@H:143]([CH3:149])[O:144][C:145]([CH3:146])([CH3:147])[CH3:148])=[O:140])[CH2:133][C:134]1[N:138]=[CH:137][NH:136][CH:135]=1)=[O:130])[CH2:122][C:123]1[CH:124]=[CH:125][CH:126]=[CH:127][CH:128]=1)=[O:119])[CH2:106][CH2:107][CH2:108][CH2:109][NH:110][C:111]([O:113][C:114]([CH3:115])([CH3:116])[CH3:117])=[O:112])=[O:103])[CH2:98][C:99](=[O:101])[NH2:100])=[O:66])[CH2:58][C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1)=[O:55])[CH2:50][C:51](=[O:53])[NH2:52])=[O:47])[CH2:41][CH2:42][C:43](=[O:45])[NH2:44])=[O:38])[C@@H:30]([CH3:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:27])[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[CH:17][CH:16]=1)=[O:11])[C@@H:3]([CH3:9])[O:4][C:5]([CH3:8])([CH3:7])[CH3:6]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 10906Tert-Butyl nitriteHCID 81531Diisopropylethylamine2×HCID 131709993HCID 131709993, compoundHCID 178455940HCID 178455940, compound

Product 1

HCID 131709995HCID 131709995, compound

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
-17.5 °C

Procedure

800 mg of Z-Thr(tBu)-Tyr(tBu)-Thr(tBu)-Gln-Asn-Phe-NH-NH2 are dissolved in 18 ml of dimethylformamide, the solution treated at -20° C. with 0.58 ml of 3N-hydrogen chloride in dioxan, and the batch then mixed with 0.16 ml of t-butylnitrite. The batch is then stirred for 15 minutes at -20 to -15° C., 0.30 ml of N,N-diisopropyl-ethylamine and 855 mg of H-Asn-Lys(BOC)-Phe-His-Thr(tBu)-Phe-Pro-Gln-Thr(tBu)-Ala-Ile-Gly-OH (acetate) in 20 ml of dimethylformamide (90% strength) are added, followed by stirring at 0° C. After one hour and after another hour, 0.075 ml of N,N-di-isopropylethylamine (a total of 0.15 ml) is added each time, and the batch is stirred at 0° C. for 15 hours. The whole is then stirred into 600 ml of ether, the precipitate is allowed to settle, and then filtered. For purification, the crude product is recrystallized once from dimethylformamide+ethyl acetate and once from dimethylformamide+aqueous 0.002N-hydrochloric acid.

Workup

  1. stirringby stirring at 0° C
  2. waitAfter one hour
  3. waitafter another hour
  4. stirringthe batch is stirred at 0° C. for 15 hours
  5. filtrationfiltered
  6. customFor purification
  7. customthe crude product is recrystallized once from dimethylformamide+ethyl acetate and once from dimethylformamide+aqueous 0.002N-hydrochloric acid

Sources & evidence

ORD record
ord-16cf4e569dba4b85b1fe450479c39c7f
Source dataset
uspto-grants-1979_07
Patent number
US04159981

Reaction notes

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