4-Methylmorpholine → Ethyl beta-[[[2-[[[4-(aminoiminomethyl)phenyl]amino]carbonyl]cyclopropyl]carbonyl]amino]-butanoate

HRID 2225976Notes

Reaction equation

HRID 2225976 reaction equation
Cl.[NH2:2][N:3]=[CH:4][C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12]([CH:14]2[CH2:16][CH:15]2[C:17]([OH:19])=O)=[O:13])=[CH:7][CH:6]=1.CN1CCOCC1.C(OC(Cl)=O)C(C)C.[NH2:35][CH:36]([CH3:43])[CH2:37][C:38]([O:40][CH2:41][CH3:42])=[O:39]>CN(C=O)C>[NH2:2][N:3]=[CH:4][C:5]1[CH:6]=[CH:7][C:8]([NH:11][C:12]([CH:14]2[CH2:16][CH:15]2[C:17]([NH:35][CH:36]([CH3:43])[CH2:37][C:38]([O:40][CH2:41][CH3:42])=[O:39])=[O:19])=[O:13])=[CH:9][CH:10]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 98103Ethyl 3-aminobutyrateHCID 700629432-[[[4-(Aminoiminomethyl)phenyl]amino]carbonyl]cyclopropyl-carboxylic acid hydrochloride

Product 1

HCID 67852831Ethyl beta-[[[2-[[[4-(aminoiminomethyl)phenyl]amino]carbonyl]cyclopropyl]carbonyl]amino]-butanoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 1.0 g (0.0035 mol) 2-[[[4-(aminoiminomethyl)phenyl]amino]carbonyl]cyclopropyl-carboxylic acid hydrochloride in 100 mL dry DMF was added 0.36 g (0.39 mL, 0.0035 mol) N-methylmorpholine and 0.48 g (0.46 mL, 0.0035 mol) isobutylchloroformate. The reaction was allowed to proceed for ten minutes at room temperature then 0.515 g (0.576 mL , 0.0035 mol) ethyl 3-aminobutyrate was added. The reaction was allowed to proceed overnight. The volatiles were removed under vacuum at 55° C. until a viscous oil remained. The residue was dissolved in water (60 mL) and purified by preparative RPHPLC. Two diastereomers were obtained and separated by HPLC. The faster eluting diastereoisomer, isomer 1, was collected and lyophilized to 0.9 g of a white solid: 1H NMR (300 MHz) d6 -DMSO δ 1.17 (m, 8H), 2.07 (m, 1H), 2.38 (m, 1H), 4.04 (m, 3 H), 7.77 (s, 4H), 8.28 (d, J=7.9), 8.80 (bs, 2H), 9.16 (bs , 2H), 10.78 (s , 1H); MS (FAB) 361.3 (MH+).

Workup

  1. waitto proceed for ten minutes at room temperature
  2. customThe volatiles were removed under vacuum at 55° C. until a viscous oil
  3. dissolutionThe residue was dissolved in water (60 mL)
  4. custompurified by preparative RPHPLC
  5. customTwo diastereomers were obtained
  6. customseparated by HPLC
  7. washThe faster eluting diastereoisomer, isomer 1
  8. customwas collected

Sources & evidence

ORD record
ord-77157e3429754dc89ce474856170beb7
Source dataset
uspto-grants-1994_09
Patent number
US05344957

Reaction notes

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