Indole-2-carboxylic acid → 1H-Indole-2-carboxylic acid [1-(Isopropyl-phenyl-carbamoylmethyl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl]-amide

HRID 264023Notes

Reaction equation

HRID 264023 reaction equation
[NH2:1][CH:2]1[C:8](=[O:9])[N:7]([CH2:10][C:11]([N:13](C(C)C)C2C=CC=CC=2)=[O:12])[C:6]2[CH:23]=[CH:24][CH:25]=[CH:26][C:5]=2[N:4](C2C=CC=CC=2)[C:3]1=[O:33].[NH:34]1[C:42]2[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=2)[CH:36]=[C:35]1[C:43]([OH:45])=O.ON1[C:51]2[CH:52]=[CH:53][CH:54]=[CH:55][C:50]=2N=N1.Cl.CN(C)[CH2:59][CH2:60][CH2:61]N=C=NCC>CN(C)C=O.C(N(CC)CC)C>[CH:5]([C:10]([C:59]1[CH:60]=[CH:61][CH:8]=[CH:2][CH:3]=1)([C:11](=[O:12])[NH2:13])[N:7]1[C:8](=[O:9])[CH:2]([NH:1][C:43]([C:35]2[NH:34][C:42]3[C:37]([CH:36]=2)=[CH:38][CH:39]=[CH:40][CH:41]=3)=[O:45])[C:3](=[O:33])[N:4]([C:5]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:6]=2)[C:51]2[CH:52]=[CH:53][CH:54]=[CH:55][C:50]1=2)([CH3:26])[CH3:6]

Participants

7

Reactant 4

HCID 72899Indole-2-carboxylic acidHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 101142752-(3-amino-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-phenyl-acetamide

Product 1

HCID 867510371H-Indole-2-carboxylic acid [1-(Isopropyl-phenyl-carbamoylmethyl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl]-amideYield 183.7%

Reagents, catalysts & solvents 2

HCID 8471TriethylamineCatalystHCID 6228DimethylformamideSolvent

Procedure

To a vigorously stirred solution of 2-{3-Amino-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo [b] [1, 4] diazepine-1-yl)-N-isopropyl-N-phenyl acetamide (0.116 g) in N,N-dimethylformamide (5 ml) at ambient temperature was added indole-2-carboxylic acid (0.0423 g, 0.262 mmol), N-hydroxybenzotriazole (0.0354 g), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.0503 g) successively. Triethylamine (8 drops) was added dropwise to maintain the basicity (pH=9) of the solution was reached. The resultant mixture was stirred at ambient temperature for five hours. The solvent was evaporated in vacuo to give a yellow oil which was purified by flash chromatography on silica gel (9 g) with an eluant of a mixture of ethyl acetate and hexane (2:3, 200 ml). Fractions containing the desired product were combined and evaporated in vacuo to give the title compound (0.141 g) as a white foam. 1H NMR (300 MHz, CDCl3): d 1.06 (d, J=7.3 Hz, 3H), 1.09 (d, J=7.3 Hz, 3H), 4.22 (d, J=16.6 Hz, 1H), 4.40(d, J=16.4 Hz, 1H), 5.02(m, 1H), 5.50(d, J=7.1 Hz, 1H), 7.02(d, J=8.1 Hz, 1H), 7.10-7.47 (m, 16H), 7.57 (d, J=6.8 Hz, 1H), 7.67 (d, J=7.8 Hz, 1H), 9.29 (br s, 1H); MS (FAB): m/z=586.0 (MH+); TLC (EtOAc/Hexane (2:3)): Rf =0.16; RP-HPLC (Vydac C-18, 25 cm×4.6 mm; 51-60% CH3CN in H2O with 0.1% TFA buffer;, 30 minutes; 1 ml/min): tf =19.5 min (to =3 min).

Workup

  1. customThe solvent was evaporated in vacuo
  2. customto give a yellow oil which
  3. customwas purified by flash chromatography on silica gel (9 g) with an eluant of a mixture of ethyl acetate and hexane (2:3, 200 ml)
  4. additionFractions containing the desired product
  5. customevaporated in vacuo

Sources & evidence

ORD record
ord-948cbdff6f5a438cad781549e9bab497
Source dataset
uspto-grants-1997_07
Patent number
US05646140

Reaction notes

Loading…