Dichloromethane → 2-(4-{2-[2-(3,5-dimethoxyphenyl)ethyl]-5H-pyrrolo[2,3-b]pyrazin-6-yl}-1H-pyrazol-1-yl)-N,N-dimethylethanamine

HRID 1052256ノート

反応式

HRID 1052256 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.[CH3:35][N:36]([CH3:53])[CH2:37][CH2:38][N:39]1[CH:43]=[C:42](B2OC(C)(C)C(C)(C)O2)[CH:41]=[N:40]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(=O)([O-])[O-].[K+].[K+]>O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[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:42]4[CH:41]=[N:40][N:39]([CH2:38][CH2:37][N:36]([CH3:53])[CH3:35])[CH:43]=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 57722832N,N-Dimethyl-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)ethan-1-amineHCID 899637236-bromo-2-[2-(3,5-dimethoxyphenyl)ethyl]-5-(phenylsulfonyl)-5H-pyrrolo[2,3-b]pyrazine

生成物 1

HCID 730562422-(4-{2-[2-(3,5-dimethoxyphenyl)ethyl]-5H-pyrrolo[2,3-b]pyrazin-6-yl}-1H-pyrazol-1-yl)-N,N-dimethylethanamine収率 22.4%

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 (from example 1, step 4, 20.0 mg, 0.0398 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complexed with dichloromethane (1:1) (1.30 mg, 1.59 μmol), N,N-dimethyl-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]ethanamine (8.44 mg, 0.0318 mmol), and potassium phosphate (13.5 mg, 0.0637 mmol) in water (0.2 mL)/1,4-dioxane (0.4 mL) was heated at 88° C. After 1 hour, the volatiles were removed under vacuum and the residues were dissolved in methanol (2.0 mL). Potassium carbonate (8.8 mg, 63.7 μmol) was added and the reaction mixture was 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 (3.0 mg) as its TFA salt. LCMS calculated for C23H29N6O2 (M+H)+: m/z=421.2. Found: 421.2.

後処理

  1. customthe volatiles were removed under vacuum
  2. dissolutionthe residues were dissolved in methanol (2.0 mL)
  3. temperaturethe reaction mixture was 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-7284a63b9363405a806ee72b31d7e1e1
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…