Ammonium Chloride → 3-(6-Dimethylaminomethyl-imidazo[1,2-a]pyridin-3-yl)-4-(1H-indol-3-yl)-pyrrole-2,5-dione

HRID 402888

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HRID 402888 반응식
CC(C)([O-])C.[K+].CO[C:9](=[O:21])[C:10]([C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[NH:14][CH:13]=1)=O.[CH3:22][N:23]([CH2:25][C:26]1[CH:27]=[CH:28][C:29]2[N:30]([C:32]([CH2:35][C:36]([NH2:38])=[O:37])=[CH:33][N:34]=2)[CH:31]=1)[CH3:24].[NH4+].[Cl-].C1CCN2C(=NCCC2)CC1>O1CCCC1.CCOC(C)=O.O>[CH3:22][N:23]([CH2:25][C:26]1[CH:27]=[CH:28][C:29]2[N:30]([C:32]([C:35]3[C:36](=[O:37])[NH:38][C:9](=[O:21])[C:10]=3[C:12]3[C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[NH:14][CH:13]=3)=[CH:33][N:34]=2)[CH:31]=1)[CH3:24]

참가 물질

9

반응물 5

HCID 25517Ammonium ChlorideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 588944Methyl 3-indoleglyoxylateHCID 23665647Potassium tert-butoxideHCID 591920412-(6-Dimethylaminomethyl-imidazo[1,2-a]pyridin-3-yl)-acetamide

생성물 1

HCID 249682363-(6-Dimethylaminomethyl-imidazo[1,2-a]pyridin-3-yl)-4-(1H-indol-3-yl)-pyrrole-2,5-dione수율 44.1%

시약·촉매·용매 3

HCID 962Water용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

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온도
0 °C

실험 절차

Potassium tert-butoxide (1.0 M in THF, 0.55 ml, 0.55 mmol, 2.7 equiv) is added dropwise at room temperature under an atmosphere of argon to a solution of (1H-indol-3-yl)-oxo-acetic acid methyl ester (45 mg, 0.22 mmol, 1.1 equiv) and of 2-(6-dimethylaminomethyl-imidazo[1,2-a]pyridin-3-yl)-acetamide (50 mg, 0.20 mmol) in anhydrous tetrahydrofuran (5.0 ml, dried over molecular sieves). The reaction mixture is stirred for 30 minutes at 0° C. It is then diluted with EtOAc and poured into a saturated aqueous NH4Cl solution. After three extractions with EtOAc, the combined organic layers are dried over Na2SO4, filtered and concentrated in vacuo. The residue is dissolved in N,N-dimethylformamide (5 ml), treated with DBU (0.27 ml, 1.8 mmol, 8.9 equiv) and heated to 110° C. for 10 minutes. After cooling, the reaction mixture is diluted with water and extracted three times with CH2Cl2. The combined organic layers are ished with brine, dried over Na2SO4, filtered and concentrated in vacuo. Purification of the residue via preparative HPLC affords the title compound (34 mg, 43%) as its trifluoroacetate salt. 1H NMR (400 MHz, d6-DMSO): δ=12.11 (s, 1H), 11.27 (s, 1H), 9.47 (br s, 1H), 8.21 (d, J=2.9 Hz, 1H), 8.05 (s, 1H), 7.78-7.76 (m, 2H), 7.73 (d, J=8.0 Hz, 1H), 7.29 (dd, J=8.0/4.0 Hz, 1H), 6.94 (t, J=8.0 Hz, 1H), 6.49 (t, J=8.0 Hz, 1H), 5.95 (d, J=8.0 Hz, 1H), 3.48-3.40 (m, 2H), 2.16 (s, 6H). MS (ES+): 386 (M+H)+.

후처리

  1. extractionAfter three extractions with EtOAc
  2. dry with materialthe combined organic layers are dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue is dissolved in N,N-dimethylformamide (5 ml)
  6. temperatureheated to 110° C. for 10 minutes
  7. temperatureAfter cooling
  8. extractionextracted three times with CH2Cl2
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customPurification of the residue via preparative HPLC

출처 및 근거

ORD 기록
ord-fb2115a2acc0472084ff9e5bd5d15723
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08742132B2

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