N-((Phenylmethoxy)carbonyl)glycylglycylglycine → Z-Gly-Gly-Gly-beta-Ala-OtBu

HRID 882676Notes

Reaction equation

HRID 882676 reaction equation
[NH:1]([C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])[CH2:2][C:3]([NH:5][CH2:6][C:7]([NH:9][CH2:10][C:11]([OH:13])=O)=[O:8])=[O:4].[C:24]([O:28][C:29](=[O:33])[CH2:30][CH2:31][NH2:32])([CH3:27])([CH3:26])[CH3:25].OC1C2N=NNC=2C=CC=1.Cl.CN(C)CCCN=C=NCC>CN(C)C=O>[NH:1]([C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])[CH2:2][C:3]([NH:5][CH2:6][C:7]([NH:9][CH2:10][C:11]([NH:32][CH2:31][CH2:30][C:29]([O:28][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:33])=[O:13])=[O:8])=[O:4]

Participants

6

Reactant 4

HCID 297872N-((Phenylmethoxy)carbonyl)glycylglycylglycineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 4192171tert-Butyl 3-aminopropanoateHCID 178418300HCID 178418300, compound

Product 1

HCID 57945504Z-Gly-Gly-Gly-beta-Ala-OtBuYield 75%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1.3 g (4.0 mmol) of Z-Gly-Gly-Gly-OH, 0.583 g (4.0 mmol) of tert-butyl-3-aminopropionate 0.651 g (4.25 mmol) of hydroxybenzotriazole and 0.81 g (4.23 mmol) of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride were weighed into a 50 mL flask then dissolved in 20 mL of dimethylformamide with magnetic stirring under a nitrogen atmosphere. After 3 hours the reaction mixture was purified in 5 mL portions by reverse phase HPLC using a 5.0 cm×25 cm C18 column. The column was run at 100 mL/min with deionized water containing 0.3% formic acid 5% acetonitrile for 10 min followed by a 15 min linear gradient from 5% acetonitrile to 90% acetonitrile. Product fractions (retention time of 19 min) were combined and solvent was removed by rotary evaporation under vacuum to give 1.35 g (75%) of the title compound. 1H NMR (d6-DMSO) 8.16 (t, J=5.2 Hz, 1H), 8.10 (t, J=5.2 Hz, 1H), 7.82 (t, J=5.2 Hz, 1H), 7.25-7.4 (m, 5H), 5.04 (s, 2H), 3.74 (d, J=5.6 Hz, 2H), 3.67 (t, J=6.4 Hz, 4H), 3.25 (q, J=6.1 Hz, 2H), 2.35 (t, J=6.8 Hz, 2H), 1.39 (s, 9H). 13C NMR (d6-DMSO) 170.45, 169.61, 169.00, 168.63, 156.49, 136.94, 128.30, 127.76, 127.69, 79.89, 65.51, 43.56, 42.10, 41.90, 34.89, 34.78, 27.70. HRMS (M+Na+) Calc. 473.2012 found 473.1995.

Workup

  1. customAfter 3 hours the reaction mixture was purified in 5 mL portions by reverse phase HPLC
  2. waitfollowed by a 15 min linear gradient from 5% acetonitrile to 90% acetonitrile
  3. customsolvent was removed by rotary evaporation under vacuum

Sources & evidence

ORD record
ord-97ccd21491ac4835a076a444eb29e256
Source dataset
uspto-grants-2012_08
Patent number
US08236319B2

Reaction notes

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