Sodium Carbonate → 3-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-(3-pyridinyl)thieno[3,2-c]pyridin-4-amine

HRID 1909929노트

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HRID 1909929 반응식
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH2:9][C:10]([N:12]1[C:20]2[C:15](=[CH:16][C:17]([C:21]3[C:25]4[C:26]([NH2:31])=[N:27][CH:28]=[C:29](I)[C:24]=4[S:23][CH:22]=3)=[CH:18][CH:19]=2)[CH2:14][CH2:13]1)=[O:11].[N:32]1[CH:37]=[CH:36][CH:35]=[C:34](B(O)O)[CH:33]=1.C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1>C(OCC)(=O)C.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH2:9][C:10]([N:12]1[C:20]2[C:15](=[CH:16][C:17]([C:21]3[C:25]4[C:26]([NH2:31])=[N:27][CH:28]=[C:29]([C:34]5[CH:33]=[N:32][CH:37]=[CH:36][CH:35]=5)[C:24]=4[S:23][CH:22]=3)=[CH:18][CH:19]=2)[CH2:14][CH2:13]1)=[O:11]

참가 물질

7

반응물 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 27343783-Pyridinylboronic acidHCID 668236633-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-iodothieno[3,2-c]pyridin-4-amine

생성물 1

HCID 534678203-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-(3-pyridinyl)thieno[3,2-c]pyridin-4-amine수율 82%

시약·촉매·용매 2

HCID 962Water용매HCID 8857Ethyl Acetate용매

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온도
120 °C

실험 절차

To a 25 mL microwave reaction tube was charged 3-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-iodothieno[3,2-c]pyridin-4-amine (150 mg, 0.274 mmol), 3-pyridinylboronic acid (33.7 mg, 0.274 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (11.19 mg, 0.014 mmol), and sodium carbonate (58.1 mg, 0.548 mmol) followed by dioxane (5 mL), and water (1 mL). The reaction was heated at 120° C. for 30 min in microwave reactor. Ethyl acetate (20 mL) was added and the layers were separated. The organic layer was washed with brine, concentrated, and the residue purified by silica gel chromatography (0%-100% EtOAc in hexanes). Product came out at 100% EtOAc, the fractions with the product was combined, evaporated to dryness to afford the title compound as a light gray solid (112 mg). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.88 (d, J=2.0 Hz, 1H) 8.62 (dd, J=4.8, 1.3 Hz, 1H) 8.04-8.18 (m, 2H) 7.97 (s, 1H) 7.56 (dd, J=7.6, 4.8 Hz, 1H) 7.51 (s, 1H) 7.39 (s, 1H) 7.14-7.32 (m, 4H) 5.64 (br. s., 2H) 4.32 (t, J=8.3 Hz, 2H) 3.97 (s, 2H) 3.29 (t, 2H).

후처리

  1. customthe layers were separated
  2. washThe organic layer was washed with brine
  3. concentrationconcentrated
  4. customthe residue purified by silica gel chromatography (0%-100% EtOAc in hexanes)
  5. customevaporated to dryness

출처 및 근거

ORD 기록
ord-5d7f10dd82634210a304896caeda0807
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08598156B2

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