4-Methylmorpholine → Methyl-3-[[4-[[4-(aminoiminomethyl)phenyl]amino]-1,4-dioxobutyl]amino]-4-methoxypentanoate

HRID 1941554Notes

Reaction equation

HRID 1941554 reaction equation
Cl.[NH2:2][N:3]=[CH:4][C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12](=[O:18])[CH2:13][CH2:14][C:15]([OH:17])=O)=[CH:7][CH:6]=1.CN1CC[O:23][CH2:22]C1.ClC(OCC(C)C)=O.[CH3:34][O:35][C:36](=[O:44])[CH2:37][CH:38]([NH2:43])[CH2:39][CH2:40]OC.CN(C1C=CC=CN=1)C>CN(C=O)C>[CH3:34][O:35][C:36](=[O:44])[CH2:37][CH:38]([NH:43][C:15](=[O:17])[CH2:14][CH2:13][C:12]([NH:11][C:8]1[CH:7]=[CH:6][C:5]([CH:4]=[N:3][NH2:2])=[CH:10][CH:9]=1)=[O:18])[CH:39]([O:23][CH3:22])[CH3:40]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 218852-DimethylaminopyridineHCID 62365Isobutyl chloroformateHCID 21834688Methyl-5-methoxy-3-aminovalerateHCID 699519434-[(4-(Aminoiminomethyl)phenyl)amino]-4-oxobutanoic acid hydrochloride

Product 1

HCID 70062635Methyl-3-[[4-[[4-(aminoiminomethyl)phenyl]amino]-1,4-dioxobutyl]amino]-4-methoxypentanoateYield 40%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-[[4-(Aminoiminomethyl)phenyl]amino]-4-oxobutanoic acid hydrochloride prepared in Example 1, Step 1 (5.0 g, 18.5 mmol) was added to dry DMF (250 ml) followed by N-methylmorpholine (1.7 g, 18.5 mmol) and isobutyl chloroformate (2.8 g, 17 mmol) at 25° C. The mixture was stirred for 5 min. Methyl-5-methoxy-3-aminovalerate (3.0 g, 18.5 mmol) was added followed by dimethylaminopyridine. After 1 h, the solvent was removed under reduced pressure and the product purified by reverse phase chromatography (0.05% TFA water/acetonitrile) to result in 2.8 g of a white solid: 1H NMR (d6 -DMSO) δ1.74 (m, 2H), 2.4 (m, 4H), 2.6 (m, 2H), 3.16 (s, 3H), 3.33 (m, 2H), 3.56 (s, 3H), 4.12 (m, 1H), 7.78 (s, 4H), 7.81 (d, 1H, J=8.5 Hz), 9.02 (bs, 2H), 9.15 (bs, 2H), 10.40 (s, 1H); MS (FAB) m/z 379.5 (MH+).

Workup

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

Sources & evidence

ORD record
ord-11e64776419240119b54e0355649809f
Source dataset
uspto-grants-1997_12
Patent number
US05703125

Reaction notes

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