Triethylamine → 3-{2-[2-(3,5-dimethoxyphenyl)ethyl]-5H-pyrrolo[2,3-b]pyrazin-6-yl}-N,N-diethylprop-2-yn-1-amine

HRID 1052248ノート

反応式

HRID 1052248 の反応式
[CH2:1]([N:3]([CH2:7][CH3:8])[CH2:4][C:5]#[CH:6])[CH3:2].C(N(CC)CC)C.Br[C:17]1[N:37](S(C2C=CC=CC=2)(=O)=O)[C:20]2=[N:21][CH:22]=[C:23]([CH2:25][CH2:26][C:27]3[CH:32]=[C:31]([O:33][CH3:34])[CH:30]=[C:29]([O:35][CH3:36])[CH:28]=3)[N:24]=[C:19]2[CH:18]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[CH3:34][O:33][C:31]1[CH:32]=[C:27]([CH2:26][CH2:25][C:23]2[N:24]=[C:19]3[CH:18]=[C:17]([C:6]#[C:5][CH2:4][N:3]([CH2:7][CH3:8])[CH2:1][CH3:2])[NH:37][C:20]3=[N:21][CH:22]=2)[CH:28]=[C:29]([O:35][CH3:36])[CH:30]=1

参加物

8

反応物 4

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 20010DietylaminopropinHCID 899637236-bromo-2-[2-(3,5-dimethoxyphenyl)ethyl]-5-(phenylsulfonyl)-5H-pyrrolo[2,3-b]pyrazine

生成物 1

HCID 730559583-{2-[2-(3,5-dimethoxyphenyl)ethyl]-5H-pyrrolo[2,3-b]pyrazin-6-yl}-N,N-diethylprop-2-yn-1-amine収率 20%

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418476HCID 178418476、化合物触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
60 °C

実験手順

A solution of N,N-diethylprop-2-yn-1-amine (10.6 mg, 95.5 μmol), bis(triphenylphosphine)palladium(II) chloride (2.8 mg, 4.0 μmol), copper(I) iodide (1.2 mg, 6.4 mmol), triethylamine (17.0 μL, 120 μmol), and 6-bromo-2-[2-(3,5-dimethoxyphenyl)ethyl]-5-(phenylsulfonyl)-5H-pyrrolo[2,3-b]pyrazine (from Example 1, Step 4, 40.0 mg, 79.7 μmol) in N,N-dimethylformamide (1.0 mL) was stirred at ambient temperature overnight. The reaction was quenched with saturated aq. NH4Cl, then extracted with methylene chloride. The combined organic layers were dried over MgSO4, and then concentrated. The residue was dissolved in methanol (2.0 mL) and potassium carbonate (22.0 mg, 0.159 mmol) was added. The reaction mixture was then warmed up to 60° C. After 1 hour, the crude mixture was allowed to warm to room 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 (6.0 mg, 20%) as its TFA salt. LCMS calculated for C23H29N4O2 (M+H)+: m/z=393.2. Found: 393.1.

後処理

  1. customThe reaction was quenched with saturated aq. NH4Cl
  2. extractionextracted with methylene chloride
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in methanol (2.0 mL)
  6. temperatureto warm to room temperature
  7. customwas purified on RP-HPLC (XBridge C18 column
  8. 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-c942e5f97fa74f729b66df088be2644b
出典データセット
uspto-grants-2016_07
特許番号
US09388185B2

反応ノート

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