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

HRID 1941558Notes

Reaction equation

HRID 1941558 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.CN1CCOCC1.ClC(OCC(C)C)=O.[NH2:34][CH:35]([CH2:40][S:41]([C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)(=[O:43])=[O:42])[CH2:36][C:37]([OH:39])=[O:38].CN(C1C=CC=CN=1)C>C(N(CC)CC)C.CN(C=O)C>[NH2:2][N:3]=[CH:4][C:5]1[CH:6]=[CH:7][C:8]([NH:11][C:12](=[O:18])[CH2:13][CH2:14][C:15]([NH:34][CH:35]([CH2:40][S:41]([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)(=[O:43])=[O:42])[CH2:36][C:37]([OH:39])=[O:38])=[O:17])=[CH:9][CH:10]=1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 218852-DimethylaminopyridineHCID 62365Isobutyl chloroformateHCID 542206143-Amino-4-phenylsulfonyl butanoic acidHCID 699519434-[(4-(Aminoiminomethyl)phenyl)amino]-4-oxobutanoic acid hydrochloride

Product 1

HCID 700616113-[[4-[[4-(Aminoiminomethyl)phenyl]amino]-1,4-dioxobutyl]amino]-4-phenylsulfonyl butanoic acidYield 67.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

4-[[4-(aminoiminomethyl)phenyl]amino]-4-oxobutanoic acid hydrochloride prepared in Example 1, Step 1(3.0 g, 11.3 mmol) was added to dry DMF (200 ml) followed by N-methylmorpholine (1.2 g, 11.3 mmol) and isobutyl chloroformate (1.5 g, 17 mmol) at 25° C. The mixture was stirred for 5 min. 3-Amino-4-phenylsulfonyl butanoic acid (4.0 g, 11.3 mmol) was added followed by triethylamine (2.7 g) and dimethylaminopyridine. After 1 hr, the solvent was removed under reduced pressure and the solid mass was dissolved into a mixture of acetic acid:H2O:H2O2 30% (2:2:1) and stirred at 25° C. for 48 hr. The reaction mixture was concentrated in vacuo and the residue purified by reverse phase chromatography (0.05% TFA water/acetonitrile) to result in 3.5 g of a white solid: 1H NMR (d6-DMSO) 2.25 (m, 2H), 2.53 (m, 4H), 3.55 (m, 2H), 4.33 (m, 1H), 7.44 (m, 5H), 7.79 (s, 4H), 7.99 (d, 1H,J=8.1 Hz), 9.1 (bs, 2H), 9.19 (bs, 2H), 10.42 (s, 1H); MS (FAB) m/z 461.2 (MH+).

Workup

  1. waitAfter 1 hr
  2. customthe solvent was removed under reduced pressure
  3. dissolutionthe solid mass was dissolved into a mixture of acetic acid
  4. stirringH2O:H2O2 30% (2:2:1) and stirred at 25° C. for 48 hr
  5. concentrationThe reaction mixture was concentrated in vacuo
  6. customthe residue purified by reverse phase chromatography (0.05% TFA water/acetonitrile)

Sources & evidence

ORD record
ord-b8f767db08494e7c9e4b4b159a95d24a
Source dataset
uspto-grants-1997_12
Patent number
US05703125

Reaction notes

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