O-tert-Butyl-L-tyrosine → HCID 178427565, compound

HRID 1776008Notes

Reaction equation

HRID 1776008 reaction equation
[NH2:1][C@H:2]([C:15]([OH:17])=[O:16])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[CH:6][CH:5]=1.[NH2:18][C@H:19]([C:44](O)=[O:45])[CH2:20][CH2:21][CH2:22][NH:23][C:24](=[NH:43])[NH:25][S:26]([C:29]1[C:41]([CH3:42])=[C:40]2[C:34]([O:35][C:36]([CH2:39]2)([CH3:38])[CH3:37])=[C:32]([CH3:33])[C:30]=1[CH3:31])(=[O:28])=[O:27]>CN(C=O)C>[NH2:18][C@H:19]([C:44]([NH:1][C@H:2]([C:15]([OH:17])=[O:16])[CH2:3][C:4]1[CH:5]=[CH:6][C:7]([O:10][C:11]([CH3:14])([CH3:12])[CH3:13])=[CH:8][CH:9]=1)=[O:45])[CH2:20][CH2:21][CH2:22][NH:23][C:24](=[NH:43])[NH:25][S:26]([C:29]1[C:41]([CH3:42])=[C:40]2[C:34]([O:35][C:36]([CH2:39]2)([CH3:38])[CH3:37])=[C:32]([CH3:33])[C:30]=1[CH3:31])(=[O:27])=[O:28]

Participants

4

Reactant 2

HCID 7408092O-tert-Butyl-L-tyrosineHCID 178427586HCID 178427586, compound

Product 1

HCID 178427565HCID 178427565, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Commercially available Rink Amide MBHA resin (1 g, 0.45 mmol) was measured and placed in a reaction vessel and swollen with DMF. By a manual solid phase synthesis operation, Tyr(But), Arg(Pbf) were successively condensed, and Fmoc was removed. The resin was washed with DMF, MeOH, and dried to give H-Arg(Pbf)-Tyr(But)-Rink Amide MBHA resin (1.162 g). From the obtained resin, 65.6 mg, 0.025 mmol was measured and placed in a reaction vessel. Gln(Trt), Lys(Mtt) were introduced thereto by manual solid phase synthesis process to give Fmoc-Lys(Mtt)-Gln(Trt)-Arg(Pbf)-Tyr(But)-Rink Amide MBHA resin (SEQ ID NO:175) (Mtt: methyltrityl). The obtained resin was washed with toluene, then TFA-TIS-TFE-toluene (1:5:47:47) was added and the mixture was shaken in the reaction vessel for 10 min. The processing was repeated until the solution was no longer colored with free trityl group to remove Mtt group. The resin was neutralized with 5% DIEA/toluene solution, suspended in toluene:TFE (4:1), N,N-bis-Boc-1-guanylpyrazole (31.0 mg, 0.1 mmol) was added, and the mixture was adjusted to pH 10 with DIEA, and treated overnight at room temperature. After removal of Fmoc from the obtained Fmoc-Har(Boc2)-Gln(Trt)-Arg(Pbf)-Tyr(But)-Rink Amide MBHA resin (SEQ ID NO:157), the resin was treated with Fmoc-Ambz(4)-Arg(Pbf)-Ala-Tyr(But)-Ile-Asn (Trt)-Leu-Ile-Thr (γMe,MePro)-OH (28.4 mg, 0.015 mmol) obtained in Example 3, PyAOP (27.1 mg, 0.05 mmol), 0.5 M HOAt/DMF (0.2 mL, 0.1 mmol), DIEA (34.8 μL, 0.2 mmol) at room temperature overnight. The obtained resin (92.0 mg) was treated with TFA:thioanisole:m-cresol:H2O:EDT:TIS (80:5:5:5:2.5:2.5) (0.6 mL) for 90 min, and diethyl ether was added to the reaction solution to allow precipitation of a white powder. An operation to remove ether by decantation after centrifugation was repeated twice to remove acid and scavenger. The residue was extracted with aqueous acetic acid solution, and purified by preparative HPLC using Daisopak-SP100-5-ODS-P 2×25 cm to give 2.2 mg of a white powder.

Workup

  1. customplaced in a reaction vessel
  2. customcondensed, and Fmoc
  3. customwas removed
  4. washThe resin was washed with DMF, MeOH
  5. customdried

Sources & evidence

ORD record
ord-9ce425bf112d4debb9a97a7162e3fbb6
Source dataset
uspto-grants-2016_02
Patent number
US09260500B2

Reaction notes

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