1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → Gaba Gly-Gly-Gly-beta-Ala-OtBu

HRID 882678Notes

Reaction equation

HRID 882678 reaction equation
O=C1C=CC(=O)[N:3]1[CH2:8][CH2:9][CH2:10][C:11]([OH:13])=[O:12].[NH2:14][CH2:15][C:16]([NH:18][CH2:19][C:20]([NH:22][CH2:23][C:24]([NH:26][CH2:27][CH2:28][C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])=[O:25])=[O:21])=[O:17].Cl.CN(C)CCCN=C=NCC>CN(C)C=O>[CH2:9]([CH2:8][NH2:3])[CH2:10][C:11]([OH:13])=[O:12].[NH2:14][CH2:15][C:16]([NH:18][CH2:19][C:20]([NH:22][CH2:23][C:24]([NH:26][CH2:27][CH2:28][C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])=[O:25])=[O:21])=[O:17]

Participants

5

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 34049044-Maleimidobutyric AcidHCID 57945502H-Gly-Gly-Gly-beta-Ala-OtBu

Product 1

HCID 131729859Gaba Gly-Gly-Gly-beta-Ala-OtBuYield 78.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

513 mg (2.8 mmol) of 4-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)butanoic acid, 800 mg (0.2.8 mmol) tert-butyl 3-(2-(2-(2-aminoacetamido)acetamido)acetamido)propanoate and 583 mg (3.0 mmol) N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride were disolved in 12 mL of dimethyl formamide and stirred for 3 hours. The reaction mixture was purified in four equal portions by reverse phase HPLC using a 5.0 cm×25 cm C18 column. The column was eluted at 100 mL/min with deionized water containing 0.3% formic acid and 5% acetonitrile for 10 min followed by a 13 min linear gradient from 5% acetonitrile to 33% acetonitrile. Product fractions (retention time of 21 min) were combined and solvent was removed by rotary evaporation under vacuum to give 832 mg (62%) of the title compound. 1H NMR (d6-DMSO) 8.10-8.16 (m, 2H), 8.07 (t, J=4.8 Hz, 1H), 7.0-7.15 (m, 1H), 3.747 (t, J=6.0 Hz, 3H), 3.64 (d, J=5.6 Hz, 2H), 3.41 (t, J=6.8, 2H), 3.1-3.33 (m, 1H), 3.19-3.26 (m, 2H), 2.348 (t, J=6.8, 2H), 2.132 (t, J=7.2 Hz, 2H), 1.67-1.76 (m, 2H), 1.39 (s, 9H). 13C NMR (d6-DMSO) 171.80, 170.98, 170.39, 169.48, 168.96, 168.56, 134.37, 79.83, 42.05, 41.83, 37.38, 34.82, 34.71, 32.26, 27.83, 23.95. HRMS (M+Na+) Calc. 504.2070 found 504.2046

Workup

  1. customThe reaction mixture was purified in four equal portions by reverse phase HPLC
  2. washThe column was eluted at 100 mL/min with deionized water containing 0.3% formic acid and 5% acetonitrile for 10 min
  3. waitfollowed by a 13 min linear gradient from 5% acetonitrile to 33% acetonitrile
  4. customsolvent was removed by rotary evaporation under vacuum

Sources & evidence

ORD record
ord-a71d62fbcfb944cc81a2fdec92b78411
Source dataset
uspto-grants-2012_08
Patent number
US08236319B2

Reaction notes

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