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Potassium Phosphate, Tribasic → tert-butyl 1-(6-(5-(2-fluoro-3-methoxyphenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yl)piperidin-4-ylcarbamate

HRID 1529259
ノート
印刷プレビュー

反応式

HRID 1529259 の反応式
P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][CH:18]=1)[N:15]([CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][O:20]1)[N:14]=[C:13]2[C:25]1[N:30]=[C:29]([N:31]2[CH2:36][CH2:35][CH:34]([NH:37][C:38](=[O:44])[O:39][C:40]([CH3:43])([CH3:42])[CH3:41])[CH2:33][CH2:32]2)[CH:28]=[N:27][CH:26]=1.[F:45][C:46]1[C:51]([O:52][CH3:53])=[CH:50][CH:49]=[CH:48][C:47]=1B(O)O>>[F:45][C:46]1[C:51]([O:52][CH3:53])=[CH:50][CH:49]=[CH:48][C:47]=1[C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][CH:18]=1)[N:15]([CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][O:20]1)[N:14]=[C:13]2[C:25]1[N:30]=[C:29]([N:31]2[CH2:32][CH2:33][CH:34]([NH:37][C:38](=[O:44])[O:39][C:40]([CH3:41])([CH3:42])[CH3:43])[CH2:35][CH2:36]2)[CH:28]=[N:27][CH:26]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

4

反応物 3

HCID 62657Potassium Phosphate, TribasicHCID 49857442-Fluoro-3-methoxyphenylboronic acidHCID 67959723tert-butyl 1-(6-(5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yl)piperidin-4-ylcarbamate2 回

生成物 1

HCID 86709757tert-butyl 1-(6-(5-(2-fluoro-3-methoxyphenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yl)piperidin-4-ylcarbamate収率 54%

反応条件

温度
150 °C

実験手順

To a 5 mL conical microwave vial was added potassium phosphate (Aldrich, 129 mg, 0.61 mmol), PdCl2AmPhos (17.1 mg, 0.02 mmol), tert-butyl 1-(6-(5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yl)piperidin-4-ylcarbamate (compound 1e, 135 mg, 0.24 mmol), and 2-fluoro-3-methoxyphenylboronic acid (Frontier Scientific, 45.3 mg, 0.27 mmol) which was sealed, evacuated and back-filled with N2 3×. Dioxane (2.0 mL) and water (0.4 mL) were added and the resulting mixture was heated at 150° C. for 30 min with microwave irradiation. After the reaction mixtures were filtered, the crude reaction mixture was concentrated under reduced pressure. The dark brown residue was dissolved with DMSO, filtered, and purified by HPLC (5% 0.1% TFA in water to 95% 0.1% TFA in ACN over 20 min) to give tert-butyl 1-(6-(5-(2-fluoro-3-methoxyphenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yl)piperidin-4-ylcarbamate (78.1 mg, 53.5%). MS (ESI, pos. ion) m/z: 603 (M+1). A mixture of 5N HCl in IPA (25.9 μL, 0.13 mmol), tert-butyl 1-(6-(5-(2-fluoro-3-methoxyphenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yl)piperidin-4-ylcarbamate (78.1 mg, 0.13 mmol), DCM (1.3 mL) and MeOH (1.3 mL) was heated at 80° C. for 30 min with stirring. The resulting reaction mixture was cooled to RT and concentrated to a yellow solid. The above solid was stirred with a 1:1 mixture of DCM:MeOH and applied to a pre-washed (10 mL MeOH) column of Si-propylsulfonic acid (Silicycle, Cat# R51230B). The compound was released with 30 mL of MeOH (with 2M NH3) to yield the title compound product as a yellow oil. MS (ESI, pos. ion) m/z: 419 (M+1).

後処理

  1. customwas sealed
  2. customevacuated
  3. additionback-filled with N2 3×
  4. additionDioxane (2.0 mL) and water (0.4 mL) were added
  5. customAfter the reaction mixtures
  6. filtrationwere filtered
  7. customthe crude reaction mixture
  8. concentrationwas concentrated under reduced pressure
  9. dissolutionThe dark brown residue was dissolved with DMSO
  10. filtrationfiltered
  11. custompurified by HPLC (5% 0.1% TFA in water to 95% 0.1% TFA in ACN over 20 min)

出典と根拠

ORDレコード
ord-4f4687dd0e3c41f3be3b3dd288795dfc
出典データセット
uspto-grants-2015_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09090593B2

反応ノート

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このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート