5-Bromo-2-methoxypyridine → 6-(2-methoxypyridin-5-yl)-3-((E)-styryl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indazole

HRID 1816828노트

반응식

HRID 1816828 반응식
[CH:1](/[C:9]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[N:11]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[N:10]=1)=[CH:2]\[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Br[C:27]1[CH:28]=[CH:29][C:30]([O:33][CH3:34])=[N:31][CH:32]=1.C[Sn](C)C.C[Sn](C)C>O1CCOCC1.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:34][O:33][C:30]1[CH:29]=[CH:28][C:27]([C:14]2[CH:13]=[C:12]3[C:17]([C:9](/[CH:1]=[CH:2]/[C:3]4[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=4)=[N:10][N:11]3[CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:23])([CH3:25])[CH3:24])=[CH:16][CH:15]=2)=[CH:32][N:31]=1

참가 물질

7

반응물 3

HCID 27348955-Bromo-2-methoxypyridineHCID 6327618HexamethylditinHCID 22494879((E)-styryl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indazole

생성물 1

HCID 218774306-(2-methoxypyridin-5-yl)-3-((E)-styryl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indazole수율 40%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매2회HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

실험 절차

6-(22-methoxypyridin-5-yl)-3-(((E)-styryl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-indazole was converted to 6-(2-methoxypyridin-5-yl)-3-E-styryl-1H-indazole in a similar manner to that described for Example 27(a). 1H NMR (300 MHz, CDCl3) □8.53 (d, 1H, J=2.1 Hz), 8.15 (d, 1H, J-9.2 Hz), 7.97 (dd, 1H, 1=2.6, 8.6 Hz), 7.79 (s, 1H), 7.74-7.34 (m, 8H), 6.94 (d, 1H, J=8.6 Hz). HRMS (FAB) [M+H]/z Calc'd 328.1450, found 328.1462. Anal. Calc'd, C (77.04), H (5.23), N (12.83). Found: C (77.00), H (5.28), N (12.65). The starting material was prepared as follows: A solution of 5-bromo-2-methoxypyridine (2.00 g, 6.10 mmol), hexamethylditin (1.15 g, 6.10 mmol), and Pd(PPh3)4 (0.28 g, 0.24 mmol) in degassed dioxane (10 ml) was refluxed under for 16 h. 6-Iodo-3-((E)-styryl)-1-(2-trimethylsilanylthoxymethyl)-1H-indazole (2.90 g, 6.10 mmol) was added to above mixture, followed by Pd(PPh3)4 (0.35 g 0.31 mmol). The reaction mixture was refluxed for 16 h. The mixture was then diluted with ethyl acetate (150 ml), and washed with brine (30 ml). The organics were dried over MgSO4, then concentrated under reduced pressure. Purification by silica gel chromatography gave 6-(2-methoxypyridin-5-yl)-3-((E)-styryl)-1-(2-trimethylsilanyl-ethoxymethyl)1H-indazole as a yellow solid (1.12 g, 40%). 1H NMR (300 MHz, CDCl3) δ 8.51 (d, 1H, J=2.5 Hz), 8.50 (d, 1H, J=9.1 Hz), 7.93 (dd, 1H, J=2.5, 8.6 Hz), 7.69 (s, 1H), 7.69-7.28 (m, 8H), 6.89 (d, 1H, J=8.6 Hz), 5.83 (s, 2H), 4.03 (s, 3H), 3.64 (t, 2H, J=8.3 Hz), 0.93 (t, 2H, 1=8.3 Hz), −0.03 (s, 9H).

후처리

  1. customThe starting material was prepared
  2. temperatureThe reaction mixture was refluxed for 16 h
  3. washwashed with brine (30 ml)
  4. dry with materialThe organics were dried over MgSO4
  5. concentrationconcentrated under reduced pressure
  6. customPurification by silica gel chromatography

출처 및 근거

ORD 기록
ord-d37b9bd26d0c42b0be4c221aab6b7589
출처 데이터셋
uspto-grants-2005_04
특허 번호
US06884890B2

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