4-(4-Methoxybenzyloxy)-2-(methylsulfonyl)-6-(trimethylstannyl)pyrimidine → 5-(2,6-difluorophenyl)-3-(6-(4-methoxybenzyloxy)-2-(methylsulfonyl)pyrimidin-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

HRID 1529435노트

반응식

HRID 1529435 반응식
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][O:19]1)[N:13]=[C:12]2I.[CH3:25][O:26][C:27]1[CH:48]=[CH:47][C:30]([CH2:31][O:32][C:33]2[CH:38]=[C:37]([Sn](C)(C)C)[N:36]=[C:35]([S:43]([CH3:46])(=[O:45])=[O:44])[N:34]=2)=[CH:29][CH:28]=1>CN(C=O)C.C(Cl)Cl.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>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][O:19]1)[N:13]=[C:12]2[C:37]1[CH:38]=[C:33]([O:32][CH2:31][C:30]2[CH:29]=[CH:28][C:27]([O:26][CH3:25])=[CH:48][CH:47]=2)[N:34]=[C:35]([S:43]([CH3:46])(=[O:45])=[O:44])[N:36]=1

참가 물질

7

반응물 2

HCID 679579354-(4-Methoxybenzyloxy)-2-(methylsulfonyl)-6-(trimethylstannyl)pyrimidineHCID 679597535-(2,6-difluoro-phenyl)-3-iodo-1-(tetrahydro-pyran-2-yl)-1H-indazole

생성물 1

HCID 679598545-(2,6-difluorophenyl)-3-(6-(4-methoxybenzyloxy)-2-(methylsulfonyl)pyrimidin-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole수율 88.3%

시약·촉매·용매 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418397HCID 178418397, 화합물촉매HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

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온도
100 °C

실험 절차

A glass microwave reaction vessel was charged with 5-(2,6-difluorophenyl)-3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (347 mg, 0.788 mmol) and 4-(4-methoxybenzyloxy)-2-(methylsulfonyl)-6-(trimethylstannyl)pyrimidine (360 mg, 0.788 mmol) in DMF (3 mL) followed by Pd(PPh3)4 (45.5 mg, 0.039 mmol) and CuI (31 mg, 0.158 mmol). The reaction was stirred and heated in a Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 100° C. for 30 min. The mixture was diluted with DCM and washed with water, brine, dried with MgSO4, filtered and concentrated. The residue was purified with silica gel chromatography (eluting with 10-30% EtOAc in Hexanes) to give 5-(2,6-difluorophenyl)-3-(6-(4-methoxybenzyloxy)-2-(methylsulfonyl)pyrimidin-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (422 mg, 0.696 mmol, 88% yield) as a yellow solid. MS (ESI, pos. ion) m/z: 606.5 (M+1).

후처리

  1. customA glass microwave reaction vessel
  2. washwashed with water, brine
  3. dry with materialdried with MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified with silica gel chromatography (eluting with 10-30% EtOAc in Hexanes)

출처 및 근거

ORD 기록
ord-9decb2724955488cbde88722cc69ebef
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09090593B2

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