Pyrazole → 2-(Methylsulfanyl)-7-(1H-pyrazol-1-yl)pyrrolo[2,1-f][1,2,4]triazine

HRID 1262339ノート

反応式

HRID 1262339 の反応式
Br[C:2]1[N:10]2[C:5]([CH:6]=[N:7][C:8]([S:11][CH3:12])=[N:9]2)=[CH:4][CH:3]=1.[NH:13]1[CH:17]=[CH:16][CH:15]=[N:14]1.C(=O)([O-])[O-].[Cs+].[Cs+]>[Cu]I.CN(C=O)C>[CH3:12][S:11][C:8]1[N:7]=[CH:6][C:5]2=[CH:4][CH:3]=[C:2]([N:13]3[CH:17]=[CH:16][CH:15]=[N:14]3)[N:10]2[N:9]=1

参加物

6

反応物 3

HCID 1048PyrazoleHCID 10796Cesium carbonateHCID 574161287-Bromo-2-(methylsulfanyl)pyrrolo[2,1-f][1,2,4]triazine

生成物 1

HCID 574161022-(Methylsulfanyl)-7-(1H-pyrazol-1-yl)pyrrolo[2,1-f][1,2,4]triazine

試薬・触媒・溶媒 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
110 °C

実験手順

To a RB flask under argon were introduced 7-Bromo-2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazine (300 mg, 1 mmol), 1H-Pyrazole (88.5 mg, 1.30 mmol), Cesium carbonate (801 mg, 2.46 mmol), Copper(I) iodide (50 mg, 0.3 mmol) and DMF (5 mL). The mixture was degassed for few minutes and heated at 110° C. overnight under argon. Solvent was removed and the mixture was taken in EtOAc and was passed through a pad of celite. Solvent evaporation gave the crude product which was purified by flash chromatography (ISCO, hexane :EtOAc 3:1). 2-Methylsulfanyl-7-pyrazol-1-yl-pyrrolo[2,1-f][1,2,4]triazine was isolated as a yellow syrup (23, 8%). LCMS (E/I+) 232 (M+H). 2-Methoxy-4-(4-morpholin-4-yl-piperidin-1-yl)-phenylamine (47.1 mg, 0.162 mmol), 2-Methanesulfinyl-7-pyrazol-1-yl-pyrrolo[2,1-f][1,2,4]triazine (20 mg, 0.08 mmol), N,N-Diisopropylethylamine (30 uL, 0.2 mmol) and 1-Methoxy-2-propanol (200 uL,) were combined in a microwave vial. The reaction was microwaved at 200° C. for 2.5 hours, taken up in DMSO, purified by Gilson RP-HPLC. The product, [2-Methoxy-4-(4-morpholin-4-yl-piperidin-1-yl)-phenyl]-(7-pyrazol-1-yl-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-amine was isolated as a tan solid (8 mg, 21%). LCMS (E/I+) 475 (M+H). NMR 1H (DMSO-d6)-9.75 (br s, 1H), 8.94 (s, 1H), 8.58 (d, 1H, J=2.09 Hz), 7.94 (s, 1H), 7.83 (s, 1H), 7.67 (d, 1H, J=8.72 Hz), 6.94 (s, 2H), 6.70 (s, 1H), 6.60 (s, 1H), 6.52 (d, 1H, J=8.74 Hz), 4.04-3.13 (series of m, s along with the water peak, 14H), 2.71 (m, 2H), 2.15 (d, 2H, J=11.30 Hz), 1.72 (m, 2H).

後処理

  1. customThe mixture was degassed for few minutes
  2. customSolvent was removed
  3. customSolvent evaporation
  4. customgave the crude product which
  5. customwas purified by flash chromatography (ISCO, hexane :EtOAc 3:1)

出典と根拠

ORDレコード
ord-a4902d445ee748e29a438758b35f4a16
出典データセット
uspto-grants-2013_06
特許番号
US08471005B2

反応ノート

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