Dichloromethane → 2-[2-(3,5-dimethoxyphenyl)ethyl]-6-[1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl]-5H-pyrrolo[2,3-b]pyrazine

HRID 1052252ノート

反応式

HRID 1052252 の反応式
Br[C:2]1[N:22](S(C2C=CC=CC=2)(=O)=O)[C:5]2=[N:6][CH:7]=[C:8]([CH2:10][CH2:11][C:12]3[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[C:14]([O:20][CH3:21])[CH:13]=3)[N:9]=[C:4]2[CH:3]=1.ClCCl.[O:35]1[CH2:40][CH2:39][CH:38]([N:41]2[CH:45]=[C:44](B3OC(C)(C)C(C)(C)O3)[CH:43]=[N:42]2)[CH2:37][CH2:36]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(=O)([O-])[O-].[K+].[K+]>O.Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].O1CCOCC1>[CH3:19][O:18][C:16]1[CH:17]=[C:12]([CH2:11][CH2:10][C:8]2[N:9]=[C:4]3[CH:3]=[C:2]([C:44]4[CH:43]=[N:42][N:41]([CH:38]5[CH2:39][CH2:40][O:35][CH2:36][CH2:37]5)[CH:45]=4)[NH:22][C:5]3=[N:6][CH:7]=2)[CH:13]=[C:14]([O:20][CH3:21])[CH:15]=1

参加物

9

反応物 5

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 62657Potassium Phosphate, TribasicHCID 457884961-(Tetrahydro-2H-pyran-4-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 899637236-bromo-2-[2-(3,5-dimethoxyphenyl)ethyl]-5-(phenylsulfonyl)-5H-pyrrolo[2,3-b]pyrazine

生成物 1

HCID 730562402-[2-(3,5-dimethoxyphenyl)ethyl]-6-[1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl]-5H-pyrrolo[2,3-b]pyrazine収率 19.4%

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
88 °C

実験手順

A stirred mixture of 6-bromo-2-[2-(3,5-dimethoxyphenyl)ethyl]-5-(phenylsulfonyl)-5H-pyrrolo[2,3-b]pyrazine (15.0 mg, 29.8 μmol), [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) complexed with dichloromethane (1:1) (1.30 mg, 1.59 μmol), 1-(tetrahydro-2H-pyran-4-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (8.9 mg, 32.0 μmol), and potassium phosphate (13.5 mg, 63.6 μmol) in water (0.2 mL)/1,4-dioxane (0.40 mL) was heated at 88° C. After 1 hour, the volatiles were removed under vacuum and the residues were dissolved in methanol (1 mL). Potassium carbonate (8.8 mg, 63.7 μmol) was added and the reaction mixture was then warmed up to 60° C. After 1 hour, the reaction mixture was cooled to ambient temperature and was purified on RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.05% TFA, at flow rate of 30 mL/min) to give the desired product (2.5 mg) as its TFA salt. LCMS calculated for C24H28N5O3 (M+H)+: m/z=434.2. Found: 434.2.

後処理

  1. customthe volatiles were removed under vacuum
  2. dissolutionthe residues were dissolved in methanol (1 mL)
  3. temperaturethe reaction mixture was then warmed up to 60° C
  4. waitAfter 1 hour
  5. temperaturethe reaction mixture was cooled to ambient temperature
  6. customwas purified on RP-HPLC (XBridge C18 column
  7. washeluting with a gradient of acetonitrile/water containing 0.05% TFA, at flow rate of 30 mL/min)

出典と根拠

ORDレコード
ord-9119fed60c0e4933a3edb4fe29b1b3b6
出典データセット
uspto-grants-2016_07
特許番号
US09388185B2

反応ノート

読み込み中…