Cesium carbonate → HCID 66806547, 화합물

HRID 1057190

반응식

HRID 1057190 반응식
[OH:1][C:2]1[CH:3]=[C:4](/[C:8](/[CH2:38][CH3:39])=[C:9](\[C:25]2[CH:30]=[CH:29][C:28](/[CH:31]=[CH:32]/[C:33]([O:35][CH2:36][CH3:37])=[O:34])=[CH:27][CH:26]=2)/[C:10]2[CH:11]=[C:12]3[C:16](=[CH:17][CH:18]=2)[N:15]([CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][O:20]2)[N:14]=[CH:13]3)[CH:5]=[CH:6][CH:7]=1.C([O-])([O-])=O.[Cs+].[Cs+].I[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][N:48]=1.N1C=CC=CC=1CC(=O)C>CS(C)=O>[N:48]1[CH:49]=[CH:50][CH:51]=[CH:52][C:47]=1[O:1][C:2]1[CH:3]=[C:4](/[C:8](/[CH2:38][CH3:39])=[C:9](\[C:25]2[CH:26]=[CH:27][C:28](/[CH:31]=[CH:32]/[C:33]([O:35][CH2:36][CH3:37])=[O:34])=[CH:29][CH:30]=2)/[C:10]2[CH:11]=[C:12]3[C:16](=[CH:17][CH:18]=2)[N:15]([CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][O:20]2)[N:14]=[CH:13]3)[CH:5]=[CH:6][CH:7]=1

참가 물질

6

반응물 4

HCID 10796Cesium carbonateHCID 959101-(Pyridin-2-yl)propan-2-oneHCID 2211262-IodopyridineHCID 66794676HCID 66794676, 화합물2회

생성물 1

HCID 66806547HCID 66806547, 화합물수율 64.4%

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매

반응 조건

온도
80 °C

실험 절차

A mixture of (E)-ethyl 3-(4-((E)-2-(3-hydroxyphenyl)-1-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)but-1-en-1-yl)phenyl)acrylate (300 mg, 0.57 mmol; Compound 346, Step 1), CuBr (3.6 mg, 0.025 mmol), Cs2CO3 (320 mg, 0.98 mmol), 2-iodopyridine (103 mg, 0.50 mmol), 1-(pyridin-2-yl)propan-2-one (15 mg, 0.11 mmol), and DMSO (1 mL) was degassed with three vacuum/N2 cycles, heated at 80° C. for 5 h, heated at 90° C. for 2 h, and then stirred at rt for 14 h. The reaction was diluted with EtOAc and filtered through Celite. The organic filtrate was washed with H2O (50 mL), washed with brine (40 mL), dried (MgSO4), filtered, concentrated, and purified by silica gel chromatography (10%-30% EtOAc in hexanes) to give 193 mg of (E)-ethyl 3-(4-((E)-2-(3-(pyridin-2-yloxy)phenyl)-1-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)but-1-en-1-yl)phenyl)acrylate as a white foam. 1H NMR (400 MHz, DMSO-d6): δ 8.13 (dd, 1H), 8.11 (s, 1H), 7.69-7.75 (m, 2H), 7.64 (s, 1H), 7.52 (d, 1H), 7.44 (d, 2H), 7.30 (t, 1H), 7.23 (dd, 1H), 7.06-7.10 (m, 2H), 6.90-6.95 (m, 3H), 6.85-6.88 (m, 1H), 6.65 (d, 1H), 6.52 (d, 1H), 5.85 (d, 1H), 4.16 (q, 2H), 3.87-3.92 (m, 1H), 3.70-3.78 (m, 1H), 2.38-2.48 (m, 3H), 1.95-2.08 (m, 2H), 1.70-1.81 (m, 1H), 1.56-1.62 (m, 2H), 1.25 (t, 3H), 0.94 (t, 3H); LCMS: 600 (M+H)+.

후처리

  1. customwas degassed with three vacuum/N2 cycles
  2. temperatureheated at 90° C. for 2 h
  3. additionThe reaction was diluted with EtOAc
  4. filtrationfiltered through Celite
  5. washThe organic filtrate was washed with H2O (50 mL)
  6. washwashed with brine (40 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. custompurified by silica gel chromatography (10%-30% EtOAc in hexanes)

출처 및 근거

ORD 기록
ord-56d81f3c654945c8942cf01571f92089
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09399646B2

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