2-Chloro-6-(tributylstannyl)pyrazine → 3-(6-chloropyrazin-2-yl)-5-(6-cyclopropylpyrazin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

HRID 1529375노트

반응식

HRID 1529375 반응식
[CH:1]1([C:4]2[N:9]=[C:8]([C:10]3[CH:11]=[C:12]4[C:16](=[CH:17][CH:18]=3)[N:15]([CH:19]3[CH2:24][CH2:23][CH2:22][CH2:21][O:20]3)[N:14]=[C:13]4I)[CH:7]=[N:6][CH:5]=2)[CH2:3][CH2:2]1.[Cl:26][C:27]1[CH:32]=[N:31][CH:30]=[C:29]([Sn](CCCC)(CCCC)CCCC)[N:28]=1>CN(C=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.[Cu]I>[Cl:26][C:27]1[N:28]=[C:29]([C:13]2[C:12]3[C:16](=[CH:17][CH:18]=[C:10]([C:8]4[CH:7]=[N:6][CH:5]=[C:4]([CH:1]5[CH2:3][CH2:2]5)[N:9]=4)[CH:11]=3)[N:15]([CH:19]3[CH2:24][CH2:23][CH2:22][CH2:21][O:20]3)[N:14]=2)[CH:30]=[N:31][CH:32]=1

참가 물질

6

반응물 2

HCID 117740572-Chloro-6-(tributylstannyl)pyrazineHCID 679600395-(6-cyclopropylpyrazin-2-yl)-3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

생성물 1

HCID 867097793-(6-chloropyrazin-2-yl)-5-(6-cyclopropylpyrazin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole수율 35.5%

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418397HCID 178418397, 화합물촉매HCID 6228Dimethylformamide용매

반응 조건

온도
105 °C

실험 절차

A glass microwave reaction vessel was charged with 5-(6-cyclopropylpyrazin-2-yl)-3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (140 mg, 0.31 mmol), 2-chloro-6-(tributylstannyl)pyrazine (190 mg, 0.47 mmol), Pd(PPh3)4 (18 mg, 0.016 mmol) and CuI (6 mg, 0.031 mmol) in DMF (1 mL). Argon was bubbled through the mixture for 5 min. The tube was sealed and the mixture was heated to 105° C. for 2 h. The reaction was diluted with EtOAc and water and filtered through celite. The crude was purified by silica gel chromatography, eluting with a gradient of 0-50% EtOAc in hexanes, to provide 3-(6-chloropyrazin-2-yl)-5-(6-cyclopropylpyrazin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (48 mg, 0.11 mmol, 35% yield) as a light-yellow solid. MS (ESI, pos. ion) m/z: 433.0 (M+1).

후처리

  1. customA glass microwave reaction vessel
  2. customArgon was bubbled through the mixture for 5 min
  3. customThe tube was sealed
  4. additionThe reaction was diluted with EtOAc and water
  5. filtrationfiltered through celite
  6. customThe crude was purified by silica gel chromatography
  7. washeluting with a gradient of 0-50% EtOAc in hexanes

출처 및 근거

ORD 기록
ord-7be510b86e5248bd92a2b5832f49840a
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09090593B2

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