Triethylamine → 1,3-Dihydro-3-(RS)-(5-hydroxy-2-indolylcarbonyl)amino-5-(2-fluorophenyl)-2H-1,4-benzodiazepin-2-one

HRID 1084539Notes

Reaction equation

HRID 1084539 reaction equation
[NH2:1][CH:2]1[N:8]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[F:15])[C:6]2[CH:16]=[CH:17][CH:18]=[CH:19][C:5]=2[NH:4][C:3]1=[O:20].[OH:21][C:22]1[CH:23]=[C:24]2[C:28](=[CH:29][CH:30]=1)[NH:27][C:26]([C:31](O)=[O:32])=[CH:25]2.Cl.C(N=C=NCCCN(C)C)C.C(N(CC)CC)C>CN(C)C=O.C(Cl)Cl>[OH:21][C:22]1[CH:23]=[C:24]2[C:28](=[CH:29][CH:30]=1)[NH:27][C:26]([C:31]([NH:1][CH:2]1[N:8]=[C:7]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[F:15])[C:6]3[CH:16]=[CH:17][CH:18]=[CH:19][C:5]=3[NH:4][C:3]1=[O:20])=[O:32])=[CH:25]2

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 889585-Hydroxyindole-2-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 156371501,3-dihydro-5-(2-fluorophenyl)-3-amino-2H-1,4-benzodiazepin-2-one

Product 1

HCID 142082341,3-Dihydro-3-(RS)-(5-hydroxy-2-indolylcarbonyl)amino-5-(2-fluorophenyl)-2H-1,4-benzodiazepin-2-oneYield 126.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

1,3-Dihydro-3-(RS)-amino-5-(2-fluorophenyl)-2H-1,4-benzodiazepin-2-one (100 mg, 0.37 mmole) and 5-hydroxyindole-2-carboxylic acid (75 mg, 0.44 mmole) were combined at room temperature in a mixture of 1 ml of dimethylformamide and 5 ml of methylene chloride. To this reaction mixture was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (76 mg, 0.40 mmol). The pH of the reaction mixture was then adjusted to 8.5 with triethylamine and stirring was continued at room temperature for 48 hours. The solvent was removed under reduced pressure and the residue was partitioned between ethyl acetate and 10% citric acid solution. The phases were separated and the organic layer was washed in succession with 20% citric acid solution (1×30 ml), saturated sodium bicarbonate solution (2×30 ml) and brine. The dried (MgSO4) extracts were concentrated to yield 200 mg of the product. Preparative thick layer chromatography (chloroform - ethanol - ammonia, 90:10:1, v/v) afforded the analytical sample (80 mg).

Workup

  1. customThe solvent was removed under reduced pressure
  2. customthe residue was partitioned between ethyl acetate and 10% citric acid solution
  3. customThe phases were separated
  4. washthe organic layer was washed in succession with 20% citric acid solution (1×30 ml), saturated sodium bicarbonate solution (2×30 ml) and brine
  5. dry with materialThe dried (MgSO4) extracts
  6. concentrationwere concentrated

Sources & evidence

ORD record
ord-13be909f972e4d5fbdf79bc3bb5d3044
Source dataset
uspto-grants-1991_04
Patent number
US05004741

Reaction notes

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