(+-)-Mercaptosuccinic acid → H-Tyr(tBu)-Leu-OBzl

HRID 523355

반응식

HRID 523355 반응식
[NH2:1][C@H:2]([C:7]([O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:8])[CH2:3][CH:4]([CH3:6])[CH3:5].[CH3:17][C:18]1[CH:19]=[CH:20][C:21](S(O)(=O)=O)=[CH:22][CH:23]=1.C([N:30]([CH2:33][CH3:34])CC)C.C1C=CC2N([OH:44])N=NC=2C=1.N(C(OCC1C2C(=CC=CC=2)C2C1=CC=CC=2)=O)[C@H](C(O)=O)CC1C=CC([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=CC=1.CCN=C=NCCCN(C)C.Cl.C(O)(=O)C(CC(O)=O)S.C1CCN2C(=NCCC2)CC1.S(O)(C)(=O)=O>C(Cl)(Cl)Cl.[Cl-].[Na+].O>[NH2:30][C@H:33]([C:34]([NH:1][C@H:2]([C:7]([O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:8])[CH2:3][CH:4]([CH3:6])[CH3:5])=[O:44])[CH2:17][C:18]1[CH:19]=[CH:20][C:21]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[CH:22][CH:23]=1

참가 물질

11

반응물 8

HCID 6268(+-)-Mercaptosuccinic acidHCID 6395Methanesulfonic AcidHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 6451312L-Leucine, phenylmethyl ester, 4-methylbenzenesulfonate (1:1)HCID 10895791Fmoc-L-Tyr(tBu)-OH

생성물 1

HCID 131735567H-Tyr(tBu)-Leu-OBzl

시약·촉매·용매 2

HCID 6212Chloroform용매3회HCID 57417360Sodium chloride; water용매

실험 절차

H-Leu-OBzl-TsOH salt (394 mg, 1.00 mmol) was dissolved in chloroform (10 ml), triethylamine (0.14 mL, 1.00 mmol), HOBt (14 mg, 0.10 mmol) and Fmoc-Tyr(tBu)-OH (506 mg, 1.10 mmol) were added, EDC.HCl (232 mg, 1.21 mmol) was added under ice-cooling, and the mixture was stirred at room temperature overnight. After completion of the reaction, to this solution were added under ice-cooling thiomalic acid (450 mg, 3.00 mmol) and DBU (1.49 mL, 10.00 mmol), and the mixture was stirred at room temperature for 3 hr. After completion of the reaction, to this solution was added dropwise under ice-cooling a mixture of MsOH (0.23 mL, 3.60 mmol) and chloroform (2.3 mL), chloroform (10 ml) and 20% brine (20 ml) were added to give an organic layer and an aqueous layer. Then, the aforementioned pH=9.0 washing was performed three times. The obtained organic layer was washed three times with 10% aqueous sodium carbonate solution (20 ml) and three times with 20% brine (20 ml) with stirring at room temperature, and the organic layer and the aqueous layer were partitioned. The obtained organic layer was dried over sodium sulfate and filtered to give a chloroform solution (20 ml) of H-Tyr(tBu)-Leu-OBzl. This chloroform solution was directly used in the next step.

후처리

  1. temperaturecooling
  2. customAfter completion of the reaction
  3. additionto this solution were added under ice-
  4. stirringthe mixture was stirred at room temperature for 3 hr
  5. customAfter completion of the reaction
  6. additionto this solution was added dropwise under ice-
  7. temperaturecooling
  8. additionwere added
  9. customto give an organic layer
  10. washThen, the aforementioned pH=9.0 washing
  11. washThe obtained organic layer was washed three times with 10% aqueous sodium carbonate solution (20 ml) and three times with 20% brine (20 ml)
  12. stirringwith stirring at room temperature
  13. customthe organic layer and the aqueous layer were partitioned
  14. dry with materialThe obtained organic layer was dried over sodium sulfate
  15. filtrationfiltered

출처 및 근거

ORD 기록
ord-67be36247e6542e0af2ffe054949a5a5
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09334302B2

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