Triethylamine → 2,3,5,6-Tetrafluorophenyl 3-carbamoyl-1,2-dihydro-3H-pyrrolo[3,2-e]indole-7-carboxylate

HRID 2230911Notes

Reaction equation

HRID 2230911 reaction equation
F[C:2](F)(F)[C:3]([O:5][C:6]1[C:11]([F:12])=[C:10]([F:13])[CH:9]=[C:8]([F:14])[C:7]=1[F:15])=[O:4].[C:18]([N:21]1[C:32]2[C:24](=[C:25]3[C:29](=[CH:30][CH:31]=2)[NH:28]C(C(O)=O)=[CH:26]3)[CH2:23][CH2:22]1)(=[O:20])[NH2:19].C(N(CC)CC)C>CN(C=O)C>[C:18]([N:21]1[C:32]2[C:24](=[C:25]3[C:29](=[CH:30][CH:31]=2)[NH:28][C:2]([C:3]([O:5][C:6]2[C:11]([F:12])=[C:10]([F:13])[CH:9]=[C:8]([F:14])[C:7]=2[F:15])=[O:4])=[CH:26]3)[CH2:23][CH2:22]1)(=[O:20])[NH2:19]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 139953346-Carbamoyl-3,6,7,8-tetrahydropyrrolo[3,2-e]indole-2-carboxylic acidHCID 153342582,3,5,6-Tetrafluorophenyl trifluoroacetate

Product 1

HCID 154802642,3,5,6-Tetrafluorophenyl 3-carbamoyl-1,2-dihydro-3H-pyrrolo[3,2-e]indole-7-carboxylateYield 75%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2,3,5,6-Tetrafluorophenyl trifluoroacetate (2.6 g, 10 mmol, H. B. Gamper, M. W. Reed, T. Cox, J. S. Virosco, A. D. Adams, A. A. Gall, J. K. Scholler and R. B. Meyer, Jr. Nucleic Acids Res., 1993, Vol. 21, No.1, 145-150) was added dropwise to a solution of 3-carbamoyl-1,2-dihydro-3H-pyrrolo[3,2-e]indole-7-carboxylic acid (1.4 g, 6.1 mmol, D. L. Boger, R. S. Coleman, and B. J. Invergo. J. Org. Chem., 1987, Vol.52, 1521-1530) and triethylamine (1.4 ml, 10 mmol) in 15 ml of anhydrous DMF. After 1 hr, the reaction mixture was concentrated under vacuum (0.2 mm). The residue was triturated with 2 ml of dry dichloromethane. Ethyl ether (50 ml) was added and the mixture was left at 0° C. overnight. The precipitate was collected by filtration on sintered glass funnel, washed first with 50% ether/CH2Cl2 (10 ml), then with ether (50 ml) and dried in vacuo. The product was obtained as a yellow solid (1.8 g, 75%): 1H NMR (Me2SO-d6, 200 MHz, ppm) 12.32 (s, 1H, NH), 8.13 (d, 1H, J=9 Hz, C4—H), 8.01 (m, 1H, C6F4H), 7.41 (s, 1H, C8—H), 7.26 (d, 1H, J=9 Hz, C5—H), 6.17 (s, 2H, CONH2), 3.99 (t, 2H, J=9 Hz, NCH2CH2), 3.30 (t, 2H, J=9 Hz, NCH2CH2). Anal. Calcd. for C18H11N3O3F4×2H2O: C, 50.3; H, 3.52; N, 9.7. Found; C, 50.81; H, 3.60; N, 9.95.

Workup

  1. concentrationthe reaction mixture was concentrated under vacuum (0.2 mm)
  2. customThe residue was triturated with 2 ml of dry dichloromethane
  3. additionEthyl ether (50 ml) was added
  4. waitthe mixture was left at 0° C. overnight
  5. filtrationThe precipitate was collected by filtration on sintered glass funnel
  6. washwashed first with 50% ether/CH2Cl2 (10 ml)
  7. dry with materialwith ether (50 ml) and dried in vacuo

Sources & evidence

ORD record
ord-8becf5ee14f74314ba42c455f9e44b65
Source dataset
uspto-grants-2002_07
Patent number
US06426408B1

Reaction notes

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