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 1529435ノート

反応式

HRID 1529435 の反応式
[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

参加物

7

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418397HCID 178418397、化合物触媒HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
100 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-9decb2724955488cbde88722cc69ebef
出典データセット
uspto-grants-2015_07
特許番号
US09090593B2

反応ノート

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