Sodium hydride → HCID 58215846, compound

HRID 593527Notes

Reaction equation

HRID 593527 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.[H-].[Na+].[CH3:20][C:21]1[CH:22]=[C:23]([CH:27]=[C:28]([CH3:30])[CH:29]=1)[C:24](Cl)=[O:25]>C1COCC1>[CH3:20][C:21]1[CH:22]=[C:23]([CH:27]=[C:28]([CH3:30])[CH:29]=1)[C:24]([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:25]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 810883,5-Dimethylbenzoyl ChlorideHCID 445541352-pyridin-3-yl-1H-indole-5-carbonitrile

Product 1

HCID 58215846HCID 58215846, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 2-pyridin-3-yl-1H-indole-5-carbonitrile (Example 8, 200 mg, 0.913 mmol) at 0° C. in THF (6 mL) is added 60% sodium hydride (72 mg, 1.826 mmol) and the mixture is stirred for 10 min at 0° C. The reaction mixture is then warmed to room temperature and stirred for 30 min. 3,5-Dimethyl-benzoyl chloride (460 mg, 2.740 mmol) in THF (2 mL) is added dropwise at 0° C. and the reaction is stirred at room temperature for 1 h. The reaction is quenched by adding saturated sodium bicarbonate. The THF is removed under vacuum, and the resulting residue is purified by silica gel flash chromatography (ethyl acetate-heptane, 0:1 to 1:1). The resulting product is further purified by HPLC using an X-bridge RP18 and an acetonitrile-0.1% ammonia hydroxide gradient to yield 1-(3,5-dimethyl-benzoyl)-2-pyridine-3-yl-1H-indole-5-carbonitrile. 1H NMR (400 MHz, CDCl3) δ ppm 2.25 (s, 6H), 6.88 (s, 1H), 7.10 (s, 1H), 7.14 (dd, J=7.6, 5.3 Hz, 1H), 7.22 (s, 2H), 7.50-7.56 (m, 2H), 7.70 (d, J=8.8 Hz, 1H), 8.01 (s, 1H), 8.43 (dd, J=4.8, 1.5 Hz, 1H), 8.62 (s, 1H). HRMS (ESI) m/z 352.1452 [(M+H)+: Calcd for C23H18N3O: 352.1450].

Workup

  1. temperatureThe reaction mixture is then warmed to room temperature
  2. stirringstirred for 30 min
  3. stirringthe reaction is stirred at room temperature for 1 h
  4. customThe reaction is quenched
  5. additionby adding saturated sodium bicarbonate
  6. customThe THF is removed under vacuum
  7. customthe resulting residue is purified by silica gel flash chromatography (ethyl acetate-heptane, 0:1 to 1:1)
  8. customThe resulting product is further purified by HPLC

Sources & evidence

ORD record
ord-77dc390108434127b6ba724fdab4726c
Source dataset
uspto-grants-2016_01
Patent number
US09242963B2

Reaction notes

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