Dimethylformamide → 1H-Indole-2-carboxylic acid {1-[isopropyl-(4-methoxyphenyl)-carbamoylmethyl]-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl}-amide

HRID 1599090Notes

Reaction equation

HRID 1599090 reaction equation
[NH2:1][CH:2]1[C:8](=[O:9])[N:7]([CH2:10][C:11]([N:13](C(C)C)C2C=CC(OC)=CC=2)=[O:12])[C:6]2[CH:25]=[CH:26][CH:27]=[CH:28][C:5]=2[NH:4][C:3]1=[O:29].[NH:30]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH:32]=[C:31]1[C:39]([OH:41])=O.ON1[C:47]2[CH:48]=[CH:49][CH:50]=[CH:51][C:46]=2N=N1.Cl.CN(C)[CH2:55][CH2:56][CH2:57]N=C=NCC.CN([CH:67]=[O:68])C>C(OCC)(=O)C>[CH:56]([C:10]([C:50]1[CH:49]=[CH:48][C:47]([O:68][CH3:67])=[CH:46][CH:51]=1)([C:11](=[O:12])[NH2:13])[N:7]1[C:8](=[O:9])[CH:2]([NH:1][C:39]([C:31]2[NH:30][C:38]3[C:33]([CH:32]=2)=[CH:34][CH:35]=[CH:36][CH:37]=3)=[O:41])[C:3](=[O:29])[NH:4][C:5]2[CH:28]=[CH:27][CH:26]=[CH:25][C:6]1=2)([CH3:57])[CH3:55]

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 72899Indole-2-carboxylic acidHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 189295732-(3-Amino-2,4-dioxo-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl)-acetamide

Product 1

HCID 867524091H-Indole-2-carboxylic acid {1-[isopropyl-(4-methoxyphenyl)-carbamoylmethyl]-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl}-amide

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-(3-Amino-2,4-dioxo-2,3,4,5-tetrahydro-benzo[b][1,4]-diazepin-1-yl)-N-isopropyl-N-(4-methoxyphenyl)-acetamide (350 mg, 0.883 mmol) in DMF (10 mL) were added indole-2-carboxylic acid (142 mg, 0.883 mmol), N-hydroxybenzotriazole (119 mg, 0.883 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (169 mg, 0.883 mmol) successively with stirring. The resultant mixture was stirred at ambient temperature for 18 hours. The solvent was evaporated under reduced pressure to give a yellow oil which was dissolved in ethyl acetate (60 mL), washed with water (20 mL) and brine (20 mL), dried over MgSO4, filtered and concentrated under reduced pressure to a yellow oil which solidified on standing. The crude product was triturated with boiling ethanol (20 mL), cooled, filtered, and dried to give the title compound (169 mg, 0.313 mmol) as a yellow solid: 1H NMR (300 MHz, Acetone-d6): d 10.85 (br s, 1H), 9.83 (brs, 1H), 7.67 (m, 2H), 7.53 (m, 2H), 7.37-7.20 (m, 7H), 7.04 (m, 3H), 5.28 (d, J=7.5 Hz, 1H), 4.87 (m, 1H), 4.31 (d, J=16.3 Hz, 1H), 4.13 (d, J=16.6 Hz, 1H), 3.83 (s, 3H), 1.02 (m, 6H); TLC (CH2Cl2 /CH3OH (19:1)): Rf =0.24; MS (FAB): m/z=540 (MH+).

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. customto give a yellow oil which
  3. washwashed with water (20 mL) and brine (20 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure to a yellow oil which
  7. customThe crude product was triturated with boiling ethanol (20 mL)
  8. temperaturecooled
  9. filtrationfiltered
  10. customdried

Sources & evidence

ORD record
ord-6b4fcc037bda4c2ba6db56f8475a1a27
Source dataset
uspto-grants-1998_04
Patent number
US05739129

Reaction notes

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