Water → N-Methyl-N-[1-methyl-4-(2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-1H-pyrazol-3-yl]-methanesulfonamide

HRID 1262329ノート

反応式

HRID 1262329 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.[CH3:13][N:14]([C:19]1[C:23](B2OC(C)(C)C(C)(C)O2)=[CH:22][N:21]([CH3:33])[N:20]=1)[S:15]([CH3:18])(=[O:17])=[O:16].CN(C)C=O.O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+].O>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>[CH3:13][N:14]([C:19]1[C:23]([C:2]2[N:10]3[C:5]([CH:6]=[N:7][C:8]([S:11][CH3:12])=[N:9]3)=[CH:4][CH:3]=2)=[CH:22][N:21]([CH3:33])[N:20]=1)[S:15]([CH3:18])(=[O:16])=[O:17]

参加物

8

反応物 6

HCID 962WaterHCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 57416040N-Methyl-N-[1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-3-yl]methanesulfonamideHCID 574161287-Bromo-2-(methylsulfanyl)pyrrolo[2,1-f][1,2,4]triazine

生成物 1

HCID 66711859N-Methyl-N-[1-methyl-4-(2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-1H-pyrazol-3-yl]-methanesulfonamide収率 38.1%

試薬・触媒・溶媒 1

HCID 178418397HCID 178418397、化合物触媒

反応条件

温度
95 °C

実験手順

Into a 1-Neck round-bottom flask, 7-Bromo-2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazine (0.580 g, 2.38 mmol), N-Methyl-N-[1-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazol-3-yl]-methanesulfonamide (1.50 g, 4.75 mmol), Tetrakis(triphenylphosphine)palladium(0) (0.274 g, 0.238 mmol), N,N-Dimethylformamide (10 mL, 100 mmol), 1,4-Dioxane (20 mL, 200 mmol), and 1.50 M of Sodium carbonate in Water (9.50 mL, 14.2 mmol) were added. The reaction mixture was heated at 95° C. overnight. The solvent was removed under vacuum. The reaction was partitioned with water and DCM. The organic was separated, washed with Brine and dried over Na2SO4. The solid was filtered and washed with DCM. The solvent was removed under vacuum to give a solid. The reaction mixture was purified via ISCO column chromatography with DCM and methanol as eluant (0 to 5% methanol). The collected fractions afforded N-Methyl-N-[1-methyl-4-(2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-1H-pyrazol-3-yl]-methanesulfonamide as a yellow solid (0.32 g, 38%) 1256f. Into a 8-dram vial, Methylene chloride (10 mL, 200 mmol), N-Methyl-N-[1-methyl-4-(2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-1H-pyrazol-3-yl]-methanesulfonamide (0.250 g, 0.709 mmol), and m-CPBA 70-75% (70:30, m-Chloroperbenzoic acid:3-Chlorobenzoic acid, 0.175 g, 0.709 mmol) were added. The reaction mixture was stirred at room temperature for one hour. Sat. NaHCo3 and DCM was added. The organic was separated, washed with Brine and dried over Na2SO4. The solid was filtered and washed with DCM. The solvent was removed under vacuum to afford a yellow solid.

後処理

  1. customThe solvent was removed under vacuum
  2. customThe reaction was partitioned with water and DCM
  3. customThe organic was separated
  4. washwashed with Brine
  5. dry with materialdried over Na2SO4
  6. filtrationThe solid was filtered
  7. washwashed with DCM
  8. customThe solvent was removed under vacuum
  9. customto give a solid
  10. customThe reaction mixture was purified via ISCO column chromatography with DCM and methanol as eluant (0 to 5% methanol)

出典と根拠

ORDレコード
ord-dcb126d8e89a4fbd94bd9cf0f6edfb50
出典データセット
uspto-grants-2013_06
特許番号
US08471005B2

反応ノート

読み込み中…