4-Methylmorpholine → 3-[[4-[[4-(Aminoiminomethyl)phenyl]amino]-1,4-dioxobutyl]amino]-butanoic acid

HRID 1941542Notes

Reaction equation

HRID 1941542 reaction equation
[NH2:1][N:2]=[CH:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:17])[CH2:12][CH2:13][C:14]([OH:16])=O)=[CH:6][CH:5]=1.CN1CCOCC1.ClC(OCC(C)C)=O.[NH2:33][CH:34]([CH3:39])[CH2:35][C:36]([OH:38])=[O:37].C(N(CC)CC)C.CN(C1C=CC=CN=1)C>CN(C=O)C>[NH2:1][N:2]=[CH:3][C:4]1[CH:5]=[CH:6][C:7]([NH:10][C:11](=[O:17])[CH2:12][CH2:13][C:14]([NH:33][CH:34]([CH3:39])[CH2:35][C:36]([OH:38])=[O:37])=[O:16])=[CH:8][CH:9]=1

Participants

8

Reactant 6

HCID 79724-MethylmorpholineHCID 8471TriethylamineHCID 10932Beta-Aminobutyric AcidHCID 218852-DimethylaminopyridineHCID 62365Isobutyl chloroformateHCID 699510564-[[4-(Aminoiminomethyl)phenyl]amino]-4-oxobutanoic acid

Product 1

HCID 700617963-[[4-[[4-(Aminoiminomethyl)phenyl]amino]-1,4-dioxobutyl]amino]-butanoic acidYield 27.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

An aliquot of 4-[[4-(aminoiminomethyl)phenyl]amino]-4-oxobutanoic acid prepared in Example 1, Step 1 (2 g) was added to dry DMF (65 ml) followed by N-methylmorpholine (0.75 g, 1 eq.) and isobutyl chloroformate (1 g) at 25° C. The mixture was stirred for 5 min. 3-Aminobutyric acid (1.1 g, 1.1 eq.) was added followed by triethylamine (1.5 g, 1.3 eq.) and dimethylaminopyridine. After 1 h, the solvent was removed under reduced pressure and the product was purified by reverse phase chromatography (0.05% TFA water/acetonitrile) to give 750 mg of white solid: 1H NMR (d6 -DMSO) δ1.06 (d, 3H, J=7 Hz), 2.2-2.6 (m, 6H), 4.05 (m, 1H), 7.8 (m, 4H), 7.85 (d, 1H, J=8 Hz), 9.05 (bs, 2H), 9.15 (bs, 2H), 10.4 (s, 1H); MS (FAB) m/z 321.1 (MH+), 236.

Workup

  1. waitAfter 1 h
  2. customthe solvent was removed under reduced pressure
  3. customthe product was purified by reverse phase chromatography (0.05% TFA water/acetonitrile)

Sources & evidence

ORD record
ord-4cd6b46fae9b464a9e67210ad624cde9
Source dataset
uspto-grants-1997_12
Patent number
US05703125

Reaction notes

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