(2,4-Difluoro-phenyl)-hydrazine → 9-Chloro-2-[2-(2,4-difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azulene

HRID 707810

반응식

HRID 707810 반응식
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:14][CH2:13][CH2:12][C:11]3[CH:10]=[C:9]([C:15]([NH2:17])=O)[S:8][C:7]=3[C:6]=2[N:18]=1.[CH3:19]C(N(C)C)=O.CN(C=O)C.[F:30][C:31]1[CH:36]=[C:35]([F:37])[CH:34]=[CH:33][C:32]=1[NH:38][NH2:39]>C1(C)C=CC=CC=1.C(O)(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:14][CH2:13][CH2:12][C:11]3[CH:10]=[C:9]([C:15]4[N:38]([C:32]5[CH:33]=[CH:34][C:35]([F:37])=[CH:36][C:31]=5[F:30])[N:39]=[CH:19][N:17]=4)[S:8][C:7]=3[C:6]=2[N:18]=1

참가 물질

6

반응물 3

HCID 588958(2,4-Difluoro-phenyl)-hydrazineHCID 22628260N,N-dimethylformamide N,N-dimethylacetamide2회HCID 582039499-Chloro-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azulene-2-carboxylic acid amide

생성물 1

HCID 579003099-Chloro-2-[2-(2,4-difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azulene수율 67%

시약·촉매·용매 2

HCID 176Acetic Acid용매HCID 1140Toluene용매

반응 조건

온도
90 °C

실험 절차

To a suspension of 9-Chloro-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azulene-2-carboxylic acid amide (22 g, 76.8 mmol) in dry toluene (250 mL) was added DMA-DMF (56.1 g, 471.4 mmol). The resulting mixture was heated to 90° C. for 2 h. After removal of the solvent and excess of DMA-DMF, the residue (13.6 g, 94.3 mmol) was dissolved in acetic acid (250 mL) and (2,4-difluorophenyl)hydrazine (16.6 g, 115.2 mmol) was added into the mixture. The mixture was stirred at 90° C. for 2 hours. After removal of the solvents, the residue was treated with EtOAc-water (500 mL, 5:1 (v/v)). The mixture was neutralized with sodium bicarbonate aqueous solution until pH=7. The suspension was filtered and the solid was washed with EtOAc (500 mL). The combined organic layers were washed with saturate sodium bicarbonate aqueous solution (300 mL), dried over sodium sulfate and filtered. The filtrate was concentrated to the crude product, which was purified by flash column (EtOAc/Hexanes=1:3) to give 9-Chloro-2-[2-(2,4-difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azulene (21.4 g, yield: 67%)1H NMR (DMSO, 400 MHz): δ8.35 (s, 1H), 7.98-7.48 (m, 4H), 7.39 (d, J=8.8 Hz, 1H), 7.05 (s, 1H), 4.38 (t, J=4.4 Hz, 2H), 3.2 (t, J=4.4 Hz, 2H). LC-MS (ESI): m/z=417 [M+H]+

후처리

  1. customAfter removal of the solvent
  2. customAfter removal of the solvents
  3. additionthe residue was treated with EtOAc-water (500 mL, 5:1 (v/v))
  4. filtrationThe suspension was filtered
  5. washthe solid was washed with EtOAc (500 mL)
  6. washThe combined organic layers were washed with saturate sodium bicarbonate aqueous solution (300 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated to the crude product, which
  10. customwas purified by flash column (EtOAc/Hexanes=1:3)

출처 및 근거

ORD 기록
ord-5990345ba24d455d9123340295c8bdd3
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09175009B2

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