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Potassium Carbonate → [3-(1-Benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-4-(2-methylsulfanyl-pyrimidin-4-yl)-pyrazol-1-yl]-acetonitrile

HRID 500741
ノート
印刷プレビュー

反応式

HRID 500741 の反応式
[CH3:1][S:2][C:3]1[N:8]=[C:7]([C:9]2[C:10]([C:14]3[CH:15]=[C:16]4[CH:22]=[CH:21][N:20]([S:23]([C:26]5[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=5)(=[O:25])=[O:24])[C:17]4=[N:18][CH:19]=3)=[N:11][NH:12][CH:13]=2)[CH:6]=[CH:5][N:4]=1.Br[CH2:33][C:34]#[N:35].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[C:26]1([S:23]([N:20]2[C:17]3=[N:18][CH:19]=[C:14]([C:10]4[C:9]([C:7]5[CH:6]=[CH:5][N:4]=[C:3]([S:2][CH3:1])[N:8]=5)=[CH:13][N:12]([CH2:33][C:34]#[N:35])[N:11]=4)[CH:15]=[C:16]3[CH:22]=[CH:21]2)(=[O:24])=[O:25])[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=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

5

反応物 3

HCID 11430Potassium CarbonateHCID 11534BromoacetonitrileHCID 1785034265-{4-[2-(methylthio)pyrimidin-4-yl]-1H-pyrazol-3-yl}-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine

生成物 1

HCID 57856275[3-(1-Benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-4-(2-methylsulfanyl-pyrimidin-4-yl)-pyrazol-1-yl]-acetonitrile収率 63.6%

試薬・触媒・溶媒 1

HCID 6228
Dimethylformamide
溶媒

反応条件

温度
75 °C

実験手順

To a solution of the 5-{4-[2-(methylthio)pyrimidin-4-yl]-1H-pyrazol-3-yl}-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine (C-1-3) (638 mg, 1.42 mmol) and bromoacetonitrile (0.5 mL, 7 mmol) in DMF was added freshly ground Potassium Carbonate (254 mg, 1.84 mmol). The resulting suspension was stirred at 75° C. for 18 hr. LCMS showed complete consumption of starting material. The mixture was partitioned between ethyl acetate and saturated aqueous NaCl. The aqueous layer was extracted with ethyl acetate twice. The combined organics were washed with water twice, saturated aqueous NaCl, dried over MgSO4 and reduced to minimum volume. The residue was purified on silica gel using a gradient of 25 to 100% methyl tert-butyl ether in hexanes as eluent to give [3-(1-Benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-4-(2-methylsulfanyl-pyrimidin-4-yl)-pyrazol-1-yl]-acetonitrile (C-1-4) (440 mg, 63%) as a crisp foam. 1H NMR (400 MHz, ACETONITRILE-d3) δ ppm 8.46 (d, J=2.02 Hz, 1H), 8.36 (d, J=5.31 Hz, 1H), 8.31 (s, 1H), 8.11-8.16 (m, 2H), 8.09 (d, J=2.02 Hz, 1H), 7.83 (d, J=4.04 Hz, 1H), 7.64-7.71 (m, 1H), 7.57 (t, J=7.71 Hz, 2H), 7.01 (d, J=5.31 Hz, 1H), 6.75 (d, J=4.04 Hz, 1H), 5.26 (s, 2H), 1.88 (s, 3H).

後処理

  1. customconsumption of starting material
  2. customThe mixture was partitioned between ethyl acetate and saturated aqueous NaCl
  3. extractionThe aqueous layer was extracted with ethyl acetate twice
  4. washThe combined organics were washed with water twice
  5. dry with materialsaturated aqueous NaCl, dried over MgSO4
  6. customThe residue was purified on silica gel using a gradient of 25 to 100% methyl tert-butyl ether in hexanes as eluent

出典と根拠

ORDレコード
ord-9da970e4d7d54e948dfd80c39f36b9ca
出典データセット
uspto-grants-2010_08
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07772246B2

反応ノート

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