Water → HCID 66780847, compound

HRID 1633857Notes

Reaction equation

HRID 1633857 reaction equation
[CH3:1][C@@H:2]1[C:8](=[O:9])[N:7]([CH3:10])[CH2:6][C:5]2[CH:11]=[C:12]([C:15]([O:17]CCCC)=O)[CH:13]=[CH:14][C:4]=2[NH:3]1.FC(F)(F)C(O)=O.[CH3:29][N:30]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH:32]=[C:31]1[CH2:39][NH:40][CH3:41].CCN(CC)CC.C1C=CC2N(O)N=NC=2C=1.O.CCN=C=NCCCN(C)C.Cl>C(Cl)Cl.CN(C=O)C.C(Cl)Cl>[CH3:29][N:30]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH:32]=[C:31]1[CH2:39][N:40]([CH3:41])[C:15]([C:12]1[CH:13]=[CH:14][C:4]2[NH:3][C@H:2]([CH3:1])[C:8](=[O:9])[N:7]([CH3:10])[CH2:6][C:5]=2[CH:11]=1)=[O:17]

Participants

10

Reactant 7

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11401058methyl((1-methyl-1H-indol-2-yl)methyl)amineHCID 86758782HCID 86758782, compound

Product 1

HCID 66780847HCID 66780847, compoundYield 86%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

To a stirred solution of ten-butyl (2R)-2,4-dimethyl-3-oxo-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine-7-carboxylate (0.75 g, 2.6 mmole) in CH2Cl2 (20 mL) was added trifluoroacetic acid (20 mL). After stirring at RT for 45 min the reaction was concentrated on the rotavap. The residue was redissolved in 4 N HCl in dioxane (50 mL), and the solution was concentrated to dryness. Trituration with Et2O, filtration, and drying under vacuo gave the crude carboxylic acid-hydrochloride salt as a white solid. To a stirred solution of this material in 1:1 DMF/CH2Cl2 (50 mL) was added 1-methyl-2-(methylaminomethyl)indole (0.42 g, 2.6 mmole), Et3N (0.73 mL, 5.2 mmole), HOBt.H2O (0.35 g, 2.6 mmole), and EDC HCl (0.5 g, 2.6 mmole). After stirring for 18 h the reaction was concentrated on the rotavap, and the residue was taken up in EtOAc (50 mL). The solution was washed sequentially with H2O (50 mL), 1.0 N Na2CO3 (50 mL), and brine (50 mL), then was dried (Na2SO4) and concentrated. Purification by flash chromatography on silica gel (EtOAc) gave the title compound (0.87 g, 86%) as a white solid: MS (ES) m/e 391.2 (M+H)+.

Workup

  1. concentrationwas concentrated on the rotavap
  2. dissolutionThe residue was redissolved in 4 N HCl in dioxane (50 mL)
  3. concentrationthe solution was concentrated to dryness
  4. filtrationTrituration with Et2O, filtration
  5. customdrying under vacuo
  6. customgave the crude carboxylic acid-hydrochloride salt as a white solid
  7. stirringAfter stirring for 18 h the reaction
  8. concentrationwas concentrated on the rotavap
  9. washThe solution was washed sequentially with H2O (50 mL), 1.0 N Na2CO3 (50 mL), and brine (50 mL)
  10. dry with materialwas dried (Na2SO4)
  11. concentrationconcentrated
  12. customPurification by flash chromatography on silica gel (EtOAc)

Sources & evidence

ORD record
ord-79a77575c29e4b8b9cbcd9769709201d
Source dataset
uspto-grants-2003_01
Patent number
US06503903B1

Reaction notes

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