Hydrochloric Acid → HCID 178427577, compound

HRID 647394Notes

Reaction equation

HRID 647394 reaction equation
[NH:1]([C:23]([O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:24])[C@H:2]([C:20]([OH:22])=O)[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[NH:19])[NH:8][S:9]([C:12]1[CH:18]=[CH:17][C:15]([CH3:16])=[CH:14][CH:13]=1)(=[O:11])=[O:10].CN1CCOCC1.ClC(OCC(C)C)=O.Cl.[NH2:49][C@H:50]([C:55]([NH:57][C@H:58]([C:63]([NH:65][C@H:66]([C:72]([NH:74][CH2:75][C:76]([NH:78][C@H:79]([C:84]([NH:86][C@H:87]([C:91]([NH2:93])=[O:92])[CH:88]([CH3:90])[CH3:89])=[O:85])[CH2:80][CH:81]([CH3:83])[CH3:82])=[O:77])=[O:73])[CH2:67][CH2:68][C:69](=[O:71])[NH2:70])=[O:64])[CH2:59][CH:60]([CH3:62])[CH3:61])=[O:56])[CH2:51][CH:52]([CH3:54])[CH3:53].C(O)C(F)(F)F>CN(C)C=O.[Pd].O.C(O)(=O)C>[NH:1]([C:23]([O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:24])[C@H:2]([C:20]([NH:49][C@H:50]([C:55]([NH:57][C@H:58]([C:63]([NH:65][C@H:66]([C:72]([NH:74][CH2:75][C:76]([NH:78][C@H:79]([C:84]([NH:86][C@H:87]([C:91]([NH2:93])=[O:92])[CH:88]([CH3:90])[CH3:89])=[O:85])[CH2:80][CH:81]([CH3:82])[CH3:83])=[O:77])=[O:73])[CH2:67][CH2:68][C:69](=[O:71])[NH2:70])=[O:64])[CH2:59][CH:60]([CH3:62])[CH3:61])=[O:56])[CH2:51][CH:52]([CH3:54])[CH3:53])=[O:22])[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[NH:19])[NH:8][S:9]([C:12]1[CH:18]=[CH:17][C:15]([CH3:16])=[CH:14][CH:13]=1)(=[O:10])=[O:11]

Participants

11

Reactant 6

HCID 313Hydrochloric Acid2×HCID 64092,2,2-TrifluoroethanolHCID 79724-Methylmorpholine2×HCID 62365Isobutyl chloroformateHCID 10919311HCID 10919311, compoundHCID 178427582HCID 178427582, compound

Product 1

HCID 178427577HCID 178427577, compound

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
-5 °C

Procedure

In 300 ml of dimethylformamide is dissolved 37.8 g (81.7 millimoles) of Z-Arg(Tos)-OH, and 8.25 g of N-methylmorpholine is added to the solution. Then, the mixture is cooled to -5° C. and 10.8 g of isobutyl chloroformate is dropped to the mixture over a period of 5 minutes. The mixture is stirred for 15 minutes and mixed with a liquid mixture formed by adding 5.9 g of N-methylmorpholine to a solution of 39.5 g (58.4 millimoles) of HCl .H-Leu-Leu-Gln-Gly-Leu-Val-NH2 [prepared by reducing the Z-compound having a melting point of 261° to 265° C. and an optical rotation [α]D25 of 43.9° (C=2, acetic acid) with equivalent amounts of HCl and trifluoroethanol in the presence of 10% Pd-C] in 400 ml of dimethylformamide. The mixture is stirred at -5° C. for 2.5 hours and added to 3 l of water. The formed precipitate is recovered by filtration, washed with methanol and dissolved in acetic acid, and the solution is added to water. The formed precipitate is recovered by filtration, washed with water and dried to obtain 52.5 g of intended Z-Arg(Tos)-Leu-Leu-Gln-Gly-Leu-Val-NH2 (the yield being 83%).

Workup

  1. additionis added to the solution
  2. additionmixed with a liquid mixture
  3. customformed
  4. stirringThe mixture is stirred at -5° C. for 2.5 hours
  5. filtrationThe formed precipitate is recovered by filtration
  6. washwashed with methanol
  7. dissolutiondissolved in acetic acid
  8. additionthe solution is added to water
  9. filtrationThe formed precipitate is recovered by filtration
  10. washwashed with water
  11. customdried

Sources & evidence

ORD record
ord-e0fc84ffc89249188c8ce1383e36310d
Source dataset
uspto-grants-1983_10
Patent number
US04407745

Reaction notes

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