4-Methylmorpholine → methyl N-[(5-amino-1-methyl-3-phenyl-1H-indol-2-yl)carbonyl]-L-leucinate

HRID 2118122Notes

Reaction equation

HRID 2118122 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7]([N+:11]([O-])=O)=[CH:8][CH:9]=2)[C:4]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[C:3]1[C:20](O)=[O:21].Cl.CN(C)CCCN=C=NCC.Cl.[CH3:36][O:37][C:38](=[O:45])[C@H:39]([CH2:41][CH:42]([CH3:44])[CH3:43])[NH2:40].CN1CCOCC1.NN>C(Cl)Cl.[Ni]>[NH2:11][C:7]1[CH:6]=[C:5]2[C:10](=[CH:9][CH:8]=1)[N:2]([CH3:1])[C:3]([C:20]([NH:40][C@H:39]([C:38]([O:37][CH3:36])=[O:45])[CH2:41][CH:42]([CH3:44])[CH3:43])=[O:21])=[C:4]2[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 9321HydrazineHCID 2723695Leucine methyl ester hydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 215435181-Methyl-5-nitro-3-phenyl-1H-indole-2-carboxylic acid

Product 1

HCID 69230365methyl N-[(5-amino-1-methyl-3-phenyl-1H-indol-2-yl)carbonyl]-L-leucinateYield 87%

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of 1-methyl-5-nitro-3-phenyl-1H-indole-2-carboxylic acid (0.56 g, 1.9 mmol), 1-[3-(dimethylamino)propyl-3-ethylcarbodiimide hydrochloride (0.47 g, 2.5 mmol), and L-leucine methyl ester hydrochloride (0.40 g, 2.2 mmol) was stirred in CH2Cl2 (20 mL). N-methylmorpholine (1.01 g, 10 mmol) was added and the mixture was stirred at room temperature overnight. The mixture was then washed with 0.05 N HCl and water. The resulting solution was dried with MgSO4 and concentrated. The residue was dissolved in 30 mL of ethanol and a large excess of Raney® nickel and hydrazine (0.6 mL, 19 mmol) were added. After stirring at room temperature for 2 h the catalyst was then removed by filtering through a short pad of Celite®521. The filtrate was concentrated to give 0.65 g (87%) of crude methyl N-[(5-amino-1-methyl-3-phenyl-1H-indol-2-yl)carbonyl]-L-leucinate as a pale yellow solid: MS (ESI) m/z 394 (MH+); HRMS calcd for C23H28N3O3: 394.2128; found (ESI+): 394.2121.

Workup

  1. washThe mixture was then washed with 0.05 N HCl and water
  2. dry with materialThe resulting solution was dried with MgSO4
  3. concentrationconcentrated
  4. dissolutionThe residue was dissolved in 30 mL of ethanol
  5. stirringAfter stirring at room temperature for 2 h the catalyst
  6. customwas then removed
  7. filtrationby filtering through a short pad of Celite®521
  8. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-27b7a4937bc9480fba001b45116f4be0
Source dataset
uspto-grants-2008_10
Patent number
US07442805B2

Reaction notes

Loading…