Hydrochloric Acid → Boc-Lys(ClZ)-Arg(Tos)-Pro-Ala-Lys(ClZ)-OBzl

HRID 722988Notes

Reaction equation

HRID 722988 reaction equation
Cl.[NH2:2][C@H:3]([C:21]([N:23]1[CH2:62][CH2:61][CH2:60][C@H:24]1[C:25]([NH:27][C@H:28]([C:30]([NH:32][C@H:33]([C:50]([O:52][CH2:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1)=[O:51])[CH2:34][CH2:35][CH2:36][CH2:37][NH:38][C:39]([O:41][CH2:42][C:43]1[CH:49]=[CH:48][CH:47]=[CH:46][C:44]=1[Cl:45])=[O:40])=[O:31])[CH3:29])=[O:26])=[O:22])[CH2:4][CH2:5][CH2:6][NH:7][C:8](=[NH:20])[NH:9][S:10]([C:13]1[CH:19]=[CH:18][C:16]([CH3:17])=[CH:15][CH:14]=1)(=[O:12])=[O:11].[NH:63]([C:84]([O:86][C:87]([CH3:90])([CH3:89])[CH3:88])=[O:85])[C@H:64]([C:81](O)=[O:82])[CH2:65][CH2:66][CH2:67][CH2:68][NH:69][C:70]([O:72][CH2:73][C:74]1[CH:80]=[CH:79][CH:78]=[CH:77][C:75]=1[Cl:76])=[O:71].ON1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1>O1CCCC1.C(Cl)(Cl)Cl.CO>[NH:63]([C:84]([O:86][C:87]([CH3:90])([CH3:89])[CH3:88])=[O:85])[C@H:64]([C:81]([NH:2][C@H:3]([C:21]([N:23]1[CH2:62][CH2:61][CH2:60][C@H:24]1[C:25]([NH:27][C@H:28]([C:30]([NH:32][C@H:33]([C:50]([O:52][CH2:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1)=[O:51])[CH2:34][CH2:35][CH2:36][CH2:37][NH:38][C:39]([O:41][CH2:42][C:43]1[CH:49]=[CH:48][CH:47]=[CH:46][C:44]=1[Cl:45])=[O:40])=[O:31])[CH3:29])=[O:26])=[O:22])[CH2:4][CH2:5][CH2:6][NH:7][C:8](=[NH:20])[NH:9][S:10]([C:13]1[CH:14]=[CH:15][C:16]([CH3:17])=[CH:18][CH:19]=1)(=[O:11])=[O:12])=[O:82])[CH2:65][CH2:66][CH2:67][CH2:68][NH:69][C:70]([O:72][CH2:73][C:74]1[CH:80]=[CH:79][CH:78]=[CH:77][C:75]=1[Cl:76])=[O:71]

Participants

8

Reactant 5

HCID 313Hydrochloric Acid2×HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 7269331Boc-Lys(2-Cl-Z)-OHHCID 178427560Arg(Tos)-Pro-Ala-Lys(ClZ)-OBzl2×

Product 1

HCID 178427525Boc-Lys(ClZ)-Arg(Tos)-Pro-Ala-Lys(ClZ)-OBzlYield 81%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 21584188Chloroform methanolSolvent

Conditions

Temperature
0 °C

Procedure

At 0° C. the solution of 746 mg (0.81 mmol) of HCl.Arg(Tos)-Pro-Ala-Lys(ClZ)-OBzl (SEQ ID NO: 12) in 50 ml of anhydrous tetrahydrofuran was adjusted to pH 9, to which the pre-cold solution of 340 mg (0.82 mmol) of Boc-Lys(ClZ)-OH, 110 mg (0.82 mmol) of 1-hydroxybenzotriazole and 170 mg (0.82 mmol) of dicyclohexylcarbodiimide in 40 ml of anhydrous tetrahydrofuran was added. The reaction mixture was stirred at 0° C. for 2 h and at room temperature for 16 h and TLC (chloroform/methanol, 10:1) indicated complete disappearance of HCl.Arg(Tos)-Pro-Ala-Lys(ClZ)-OBzl (SEQ ID NO: 12). The resulted precipitates of N,N-dicyclohexylurea were filtrated and the filtrate was diluted with 100 ml of ethyl acetate. The solution obtained was washed successively with saturated NaCO3 in water (50 ml×3), saturated NaCl in water (50 ml×3) and KHSO4 in water (5%, 50 ml×3). The separated ethyl acetate layer was dried with anhydrous MgSO4, and then evaporated. The residue was purified on sinica gel chromatography (CHCl3/CH3OH, 30/1) to provide 850 mg (81%) of the title compound as a glassy mass. Mp 78–88° C., FAB-MS (m/e) 1111.3[M+H]+, 1132.5[M+Na]+, 1010.0[M-Boc]+.

Workup

  1. customAt 0° C.
  2. additionwas added
  3. customThe resulted precipitates of N,N-dicyclohexylurea
  4. filtrationwere filtrated
  5. additionthe filtrate was diluted with 100 ml of ethyl acetate
  6. customThe solution obtained
  7. washwas washed successively with saturated NaCO3 in water (50 ml×3), saturated NaCl in water (50 ml×3)
  8. dry with materialThe separated ethyl acetate layer was dried with anhydrous MgSO4
  9. customevaporated
  10. customThe residue was purified on sinica gel chromatography (CHCl3/CH3OH, 30/1)

Sources & evidence

ORD record
ord-3053f1d50a5043fd840fcefe32231339
Source dataset
uspto-grants-2006_11
Patent number
US07138491B2

Reaction notes

Loading…