1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 24968234, compound

HRID 216679

Reaction equation

HRID 216679 reaction equation
[CH3:1][N:2]([CH2:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][C:9]([C:14]([F:17])([F:16])[F:15])=[C:8]2[CH2:18][C:19]([NH2:21])=[O:20])[CH3:3].C[O:23][C:24](=O)[C:25]([C:27]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[NH:29][CH:28]=1)=O.CC([O-])(C)C.[K+].C1CCN2C(=NCCC2)CC1>C1COCC1.CCOC(C)=O.CN(C=O)C>[CH3:1][N:2]([CH2:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][C:9]([C:14]([F:16])([F:15])[F:17])=[C:8]2[C:18]1[C:19](=[O:20])[NH:21][C:24](=[O:23])[C:25]=1[C:27]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[NH:29][CH:28]=1)[CH3:3]

Participants

8

Reactant 4

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 588944Methyl 3-indoleglyoxylateHCID 23665647Potassium tert-butoxideHCID 59192010HCID 59192010, compound

Product 1

HCID 24968234HCID 24968234, compoundYield 12.1%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of 2-(5-dimethylaminomethyl-2-trifluoromethyl-1H-indol-3-yl)-acetamide (59.2 mg, 0.198 mmol) and (1H-indol-3-yl)-oxo-acetic acid methyl ester (60.3 mg, 0.297 mmol) in anhydrous THF (4.0 mL) is added dropwise a 1 M solution of t-BuOK in THF (0.989 mL) under an argon atmosphere at 0° C., followed by the addition of DMF(1.0 mL). The resulting deep red reaction mixture is stirred for 1 h at room temperature, diluted with EtOAc, washed with a saturated aqueous NH4Cl solution and washed with brine. The aqueous layer is extracted with EtOAc and the combined organic phases are dried over Na2SO4, filtered and concentrated at reduced pressure to afford a red solid. The crude product is dissolved in DMF (1.0 mL), DBU (300 1μL) is added, and the thus obtained solution is heated for 5 min. at 100° C. After cooling, the reaction mixture is diluted with EtOAc and washed with brine. The aqueous layer is extracted with EtOAc and the combined organic phases are dried over Na2SO4, filtered and concentrated at reduced pressure to afford a red solid. Purification by flash column chromatography (silica gel, EtOAc/acetic acid/water 8:1:1) affords the title compound as an orange solid (11 mg, 0.024 mmol, 12%). 1H NMR (400 MHz, DMSO-d6, 298 K): δ=12.54 (bs, 1H), 11.78 (bs, 1H), 11.06 (bs, 1H), 7.95 (d, J=2.9 Hz, 1H), 7.36 (d, J=8.5 Hz, 1H), 7.25 (d, J=8.1 Hz, 1H), 7.06 (d, J=8.4 Hz, 1H), 6.88 (t, J=8.1 Hz, 1H), 6.84 (s, 1H), 6.51 (t, J=8.1 Hz, 1H), 6.45 (d, J=8.4 Hz, 1H), 3.10 (AB-system: δA=3.24 (d, JAB=−12.4 Hz, 1H), δB=2.97 (d, JAB=−12.4 Hz, 1H), 1.70 (s, 6H). MS (ES+): 453 (M(C24H19F3N4O2)+H)+.

Workup

  1. customThe resulting deep red reaction mixture
  2. washwashed with a saturated aqueous NH4Cl solution
  3. washwashed with brine
  4. extractionThe aqueous layer is extracted with EtOAc
  5. dry with materialthe combined organic phases are dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated at reduced pressure
  8. customto afford a red solid
  9. temperaturethe thus obtained solution is heated for 5 min. at 100° C
  10. temperatureAfter cooling
  11. washwashed with brine
  12. extractionThe aqueous layer is extracted with EtOAc
  13. dry with materialthe combined organic phases are dried over Na2SO4
  14. filtrationfiltered
  15. concentrationconcentrated at reduced pressure
  16. customto afford a red solid
  17. customPurification by flash column chromatography (silica gel, EtOAc/acetic acid/water 8:1:1)

Sources & evidence

ORD record
ord-c8da19f541e442db98b540a9615cb3cc
Source dataset
uspto-grants-2012_06
Patent number
US08193236B2

Linked notes

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