1,2-Dichloroethane → 1,4-Benzodiazepine deriv. 2

HRID 1633853Notes

Reaction equation

HRID 1633853 reaction equation
[C:1]([CH2:5][C@@H:6]1[C:12](=[O:13])[N:11]([CH3:14])[CH2:10][C:9]2[CH:15]=[C:16]([C:19]([OH:21])=O)[CH:17]=[CH:18][C:8]=2[NH:7]1)([O:3][CH3:4])=[O:2].[CH3:22][N:23]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH:25]=[C:24]1[CH2:32][NH:33][CH3:34].C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.C(Cl)CCl>CN(C=O)C.O>[C:1]([CH2:5][C@@H:6]1[C:12](=[O:13])[N:11]([CH3:14])[CH2:10][C:9]2[CH:15]=[C:16]([C:19]([N:33]([CH3:34])[CH2:32][C:24]3[N:23]([CH3:22])[C:31]4[C:26]([CH:25]=3)=[CH:27][CH:28]=[CH:29][CH:30]=4)=[O:21])[CH:17]=[CH:18][C:8]=2[NH:7]1)([O:3][CH3:4])=[O:2]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 11220043(2R)-2-[(carbomethoxy)methyl]-4-methyl-3-oxo-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine-7-carboxylic acidHCID 11401058methyl((1-methyl-1H-indol-2-yl)methyl)amine

Product 1

HCID 65398821,4-Benzodiazepine deriv. 2Yield 92%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of (2R)-2-[(carbomethoxy)methyl]-4-methyl-3-oxo-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine-7-carboxylic acid (0.4 g, 1.37 mmole) in dry DMF (10 mL) at RT was added 1-methyl-2-(methylaminomethyl)indole (0.26 g, 1.50 mmole), HOBt (0.20 g, 1.50 mmole), i-Pr2NEt (0.19 g, 1.50 mmole) and EDC (0.29 g, 1.50 mmole). After 18 hr the reaction solution was diluted with H2O (25 mL) and extracted with EtOAc (2×50 mL). The organic fractions were combined, washed sequentially with H2O and brine, then were dried (Na2SO4). Concentration under vacuum followed by chromatography on silica gel (95:5 CHCl3/MeOH) provided the title compound (0.56 g, 92%) as an off-white solid: MS (ES) m/e 449 (M+H)+.

Workup

  1. extractionextracted with EtOAc (2×50 mL)
  2. washwashed sequentially with H2O and brine
  3. dry with materialwere dried (Na2SO4)
  4. concentrationConcentration under vacuum

Sources & evidence

ORD record
ord-2b5a0371449949ff9a8fab6b1f9b4017
Source dataset
uspto-grants-2003_01
Patent number
US06503903B1

Reaction notes

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