Dicyclohexylcarbodiimide → 4-Cyano-3-methylbenzoic acid

HRID 593526

反応式

HRID 593526 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:18]([C:20]1[CH:28]=[CH:27][C:23]([C:24]([OH:26])=[O:25])=[CH:22][C:21]=1[CH3:29])#[N:19].C1CCC(N=C=NC2CCCCC2)CC1>CN(C)C1C=CN=CC=1.ClCCl>[C:18]([C:20]1[CH:28]=[CH:27][C:23]([C:24]([OH:26])=[O:25])=[CH:22][C:21]=1[CH3:29])#[N:19].[C:18]([C:20]1[CH:28]=[CH:27][C:23]([C:24]([N:8]2[C:9]3[C:14](=[CH:13][C:12]([C:16]#[N:17])=[CH:11][CH:10]=3)[CH:15]=[C:7]2[C:3]2[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=2)=[O:25])=[CH:22][C:21]=1[CH3:29])#[N:19]

参加物

7

反応物 3

HCID 10868DicyclohexylcarbodiimideHCID 102410994-Cyano-3-methylbenzoic acidHCID 445541352-pyridin-3-yl-1H-indole-5-carbonitrile

生成物 2

HCID 102410994-Cyano-3-methylbenzoic acidHCID 582157251-(4-cyano-3-methyl-benzoyl)-2-pyridin-3-yl-1H-indole-5-carbonitrile

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 6344Dichloromethane溶媒

実験手順

4-Cyano-3-methyl-benzoic acid is synthesized based on the method described in patent EP1512687A1. To a solution of 2-pyridin-3-yl-1H-indole-5-carbonitrile (20 mg, 0.09 mmol), 4-dimethylaminopyridine (22 mg, 0.01 mmol) and 4-cyano-3-methyl-benzoic acid (29 mg, 0.18 mmol) at 0° C. in dichloromethane (2 mL) is added DCC (38 mg, 0.18 mmol). After stirring for 10 min the reaction is warmed to room temperature. A precipitate forms and stirring is continued for 16 h. The mixture is filtered and the filtrate is diluted with dichloromethane (10 mL), washed with water and a saturated sodium chloride solution. The combined organic extracts are dried over sodium sulfate, filtered, and concentrated. The resulting residue is purified by silica gel flash chromatography (ethyl acetate-heptane, 0:1 to 1:1) to furnish 1-(4-cyano-3-methyl-benzoyl)-2-pyridin-3-yl-1H-indole-5-carbonitrile. 1H NMR (400 MHz, CDCl3) δ ppm 2.47 (s, 3H), 6.91 (s, 1H), 7.14 (dd, J=8.0, 4.9 Hz, 1H), 7.43-7.48 (m, 2H), 7.49-7.54 (m, 2H), 7.61 (dd, J=8.7, 1.6 Hz, 1H), 7.93 (d, J=8.6 Hz, 1H), 8.03 (d, J=1.0 Hz, 1H), 8.44 (dd, J=4.8, 1.5 Hz, 1H), 8.55 (d, J=1.8 Hz, 1H). HRMS (ESI) m/z 363.1245 [(M+H)+: Calcd for C23H15N4O: 363.1246].

後処理

  1. stirringA precipitate forms and stirring
  2. waitis continued for 16 h
  3. filtrationThe mixture is filtered
  4. additionthe filtrate is diluted with dichloromethane (10 mL)
  5. washwashed with water
  6. dry with materialThe combined organic extracts are dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe resulting residue is purified by silica gel flash chromatography (ethyl acetate-heptane, 0:1 to 1:1)

出典と根拠

ORDレコード
ord-ed28606d2636494495ca9c902ae9674c
出典データセット
uspto-grants-2016_01
特許番号
US09242963B2

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