Sodium Bicarbonate → 5-(3,4-dimethoxyphenyl)-4-(1H-indol-5-yl)nicotinonitrile

HRID 506169Notes

Reaction equation

HRID 506169 reaction equation
Cl[C:2]1[C:7]([C:8]#[N:9])=[CH:6][N:5]=[CH:4][C:3]=1[C:10]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[C:12]([O:18][CH3:19])[CH:11]=1.[NH:20]1[C:28]2[C:23](=[CH:24][C:25](B(O)O)=[CH:26][CH:27]=2)[CH:22]=[CH:21]1.C([O-])(O)=O.[Na+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:19][O:18][C:12]1[CH:11]=[C:10]([C:3]2[CH:4]=[N:5][CH:6]=[C:7]([C:2]=2[C:25]2[CH:24]=[C:23]3[C:28](=[CH:27][CH:26]=2)[NH:20][CH:21]=[CH:22]3)[C:8]#[N:9])[CH:15]=[CH:14][C:13]=1[O:16][CH3:17]

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 27343615-Indolylboronic acidHCID 251297854-Chloro-5-(3,4-dimethoxyphenyl)nicotinonitrile

Product 1

HCID 445738735-(3,4-dimethoxyphenyl)-4-(1H-indol-5-yl)nicotinonitrileYield 61%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of 4-chloro-5-(3,4-dimethoxyphenyl)nicotinonitrile (120 mg, 0.44 mmol), indole-5-boronic acid (77 mg, 0.48 mmol), Pd(PPh3)4 (25 mg, 0.022 mmol) and aqueous saturated NaHCO3 (3 mL) in DME (4.0 mL) was heated at reflux for 5 h. The reaction mixture was partitioned between water and EtOAc. The combined organics were dried over Na2SO4 and concentrated to give a brown syrup, which was purified by preparative thin-layer chromatography eluting with 3% MeOH/CH2Cl2 to give 94 mg (61%) of 5-(3,4-dimethoxyphenyl)-4-(1H-indol-5-yl)nicotinonitrile 221 as an off-white solid. MS: 356.2 (M+H); melting range: 215-217° C.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 5 h
  3. customThe reaction mixture was partitioned between water and EtOAc
  4. dry with materialThe combined organics were dried over Na2SO4
  5. concentrationconcentrated
  6. customto give a brown syrup, which
  7. customwas purified by preparative thin-layer chromatography
  8. washeluting with 3% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-2de37d4801ad49b7ba7149a54663ce39
Source dataset
uspto-grants-2010_08
Patent number
US07781591B2

Reaction notes

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