Triethylamine → N-[2,3-dihydro-5-(2,6-dimethoxy-4-methylphenyl)-1-methyl-2-oxo-1H-1,4-benzodiazepin-3-yl]-1H-2-indolecarboxamide

HRID 482473Notes

Reaction equation

HRID 482473 reaction equation
[NH2:1][CH:2]1[N:8]=[C:7]([C:9]2[C:14]([O:15][CH3:16])=[CH:13][C:12]([CH3:17])=[CH:11][C:10]=2[O:18][CH3:19])[C:6]2[CH:20]=[CH:21][CH:22]=[CH:23][C:5]=2[N:4]([CH3:24])[C:3]1=[O:25].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[NH:53]1[C:61]2[C:56](=[CH:57][CH:58]=[CH:59][CH:60]=2)[CH:55]=[C:54]1[C:62](O)=[O:63].C(N(CC)CC)C>CN(C)C=O.O>[CH3:19][O:18][C:10]1[CH:11]=[C:12]([CH3:17])[CH:13]=[C:14]([O:15][CH3:16])[C:9]=1[C:7]1[C:6]2[CH:20]=[CH:21][CH:22]=[CH:23][C:5]=2[N:4]([CH3:24])[C:3](=[O:25])[CH:2]([NH:1][C:62]([C:54]2[NH:53][C:61]3[C:56]([CH:55]=2)=[CH:57][CH:58]=[CH:59][CH:60]=3)=[O:63])[N:8]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 72899Indole-2-carboxylic acidHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 153796223-Amino-1,3-dihydro-5-(2,6-dimethoxy-4-methylphenyl)-1-methyl-1,4-benzodiazepin-2-one

Product 1

HCID 9805268N-[2,3-dihydro-5-(2,6-dimethoxy-4-methylphenyl)-1-methyl-2-oxo-1H-1,4-benzodiazepin-3-yl]-1H-2-indolecarboxamideYield 81%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 0.38 g of the laevorotatory enantiomer of 3-amino-1,3-dihydro-5-(2,6-dimethoxy-4-methylphenyl)-1-methyl-1,4-benzodiazepin-2-one in 10 ml of dimethylformamide, cooled to 50° C., are added 0.52 g of BOP and 0.19 g of indole-2-carboxylic acid, followed by 0.23 ml of triethylamine. The reaction mixture is stirred overnight at room temperature and is then poured into water and extracted with ethyl acetate, dried over sodium sulphate and evaporated to dryness. The product is purified by chromatography on a column of silica gel (eluent: dichlormethane/methanol: 95/5). The fractions of pure product are evaporated to dryness and the residue is crystallized from isopropyl ether. White crystals of (-)-N-[2,3-dihydro-5-(2,6-dimethoxy-4-methylphenyl)-1-methyl-2-oxo-1H-1,4-benzodiazepin-3-yl]-1H-indol-2-carboxamide are obtained, melting at 135° C.; Yield=81%; [α]D20 =-408 (c=0.35 in 1N HCl/CH3OH-50/50).

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialdried over sodium sulphate
  3. customevaporated to dryness
  4. customThe product is purified by chromatography on a column of silica gel (eluent: dichlormethane/methanol: 95/5)
  5. customThe fractions of pure product are evaporated to dryness
  6. customthe residue is crystallized from isopropyl ether

Sources & evidence

ORD record
ord-af3784b1032c459ba481c9d81961a642
Source dataset
uspto-grants-1998_08
Patent number
US05798353

Reaction notes

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