1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 24968234、化合物

HRID 216679ノート

反応式

HRID 216679 の反応式
[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]

参加物

8

反応物 4

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 588944Methyl 3-indoleglyoxylateHCID 23665647Potassium tert-butoxideHCID 591920102-(5-dimethylaminomethyl-2-trifluoromethyl-1H-indol-3-yl)-acetamide

生成物 1

HCID 24968234HCID 24968234、化合物収率 12.1%

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒2 回HCID 8028Tetrahydrofuran溶媒2 回HCID 8857Ethyl Acetate溶媒2 回

実験手順

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)+.

後処理

  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)

出典と根拠

ORDレコード
ord-c8da19f541e442db98b540a9615cb3cc
出典データセット
uspto-grants-2012_06
特許番号
US08193236B2

反応ノート

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