Dicyclohexylcarbodiimide → 4-Cyano-3-methylbenzoic acid

HRID 593526Notes

Reaction equation

HRID 593526 reaction equation
[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]

Participants

7

Reactant 3

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

Product 2

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

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

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].

Workup

  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)

Sources & evidence

ORD record
ord-ed28606d2636494495ca9c902ae9674c
Source dataset
uspto-grants-2016_01
Patent number
US09242963B2

Reaction notes

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