Toluene → HCID 58215694、化合物

HRID 593522

反応式

HRID 593522 の反応式
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[NH:8][C:9]3[C:14]([CH:15]=2)=[CH:13][C:12]([C:16]#[N:17])=[CH:11][CH:10]=3)[CH:2]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].C1(C)C=CC=CC=1.[C:35]([C:37]1[CH:38]=[C:39]([CH:43]=[CH:44][CH:45]=1)[C:40](Cl)=[O:41])#[N:36]>C1COCC1>[C:35]([C:37]1[CH:38]=[C:39]([CH:43]=[CH:44][CH:45]=1)[C:40]([N:8]1[C:9]2[C:14](=[CH:13][C:12]([C:16]#[N:17])=[CH:11][CH:10]=2)[CH:15]=[C:7]1[C:3]1[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=1)=[O:41])#[N:36]

参加物

6

反応物 4

HCID 1140TolueneHCID 3084833-Cyanobenzoyl chlorideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 445541352-pyridin-3-yl-1H-indole-5-carbonitrile

生成物 1

HCID 58215694HCID 58215694、化合物

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of 2-pyridin-3-yl-1H-indole-5-carbonitrile (Example 8, 210 mg, 0.96 mmol) in THF (20 mL) at room temperature is added 0.5 M KHMDS in toluene (4.10 mL, 2.05 mmol). After 30 min, 3-cyanobenzoyl chloride (510 mg, 3.08 mmol) is added. The mixture is stirred under N2 overnight. The reaction is quenched with aqueous ammonium chloride and the volatiles are removed in vacuo. The residue is redissolved in dichloromethane and poured into saturated aqueous sodium bicarbonate (100 mL). Extraction with dichloromethane, drying over sodium sulfate followed by concentration affords a residue which is purified on an XBridge RP18 using a 0.1% ammonium hydroxide in acetonitrile gradient. Further purification by silica gel flash chromatography (heptane-ethyl acetate, 3:2 to 2:3) affords 1-(3-cyano-benzoyl)-2-pyridin-3-yl-1H-indole-5-carbonitrile. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.20 (d, J=0.5 Hz, 1H), 7.22-7.26 (m, 1H), 7.55 (t, J=7.8 Hz, 1H), 7.73-7.79 (m, 2H), 7.84 (d, 1H), 7.92-7.98 (m, 2H), 8.11 (t, J=1.5 Hz, 1H), 8.29-8.33 (m, 1H), 8.39 (dd, J=4.8, 1.5 Hz, 1H), 8.60 (dd, J=2.3, 0.8 Hz, 1H). HRMS (ESI) m/z 349.1106 [(M+H)+ Calcd for C22H13N4O: 349.1089].

後処理

  1. customThe reaction is quenched with aqueous ammonium chloride
  2. customthe volatiles are removed in vacuo
  3. dissolutionThe residue is redissolved in dichloromethane
  4. additionpoured into saturated aqueous sodium bicarbonate (100 mL)
  5. extractionExtraction with dichloromethane
  6. dry with materialdrying over sodium sulfate
  7. concentrationfollowed by concentration
  8. customaffords a residue which
  9. customis purified on an XBridge
  10. customFurther purification by silica gel flash chromatography (heptane-ethyl acetate, 3:2 to 2:3)

出典と根拠

ORDレコード
ord-f042297fd86c4107a25e7381223dbdde
出典データセット
uspto-grants-2016_01
特許番号
US09242963B2

関連ノート

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