Potassium Phosphate, Tribasic → 4-Chloro-6-(4-methoxyphenyl)-2-(4-phenoxyphenyl)nicotinonitrile

HRID 81053Notes

Reaction equation

HRID 81053 reaction equation
[Cl:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([C:10]2[CH:15]=[CH:14][C:13]([O:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[CH:12][CH:11]=2)[N:5]=[C:4](Cl)[CH:3]=1.[CH3:24][O:25][C:26]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28][CH:27]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C)C=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[Cl:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([C:10]2[CH:15]=[CH:14][C:13]([O:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[CH:12][CH:11]=2)[N:5]=[C:4]([C:29]2[CH:30]=[CH:31][C:26]([O:25][CH3:24])=[CH:27][CH:28]=2)[CH:3]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 201262(4-Methoxyphenyl)boronic acidHCID 866656924,6-Dichloro-2-(4-phenoxyphenyl)nicotinonitrile

Product 1

HCID 669269644-Chloro-6-(4-methoxyphenyl)-2-(4-phenoxyphenyl)nicotinonitrileYield 26%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 4,6-dichloro-2-(4-phenoxyphenyl)nicotinonitrile (56.8 mg, 0.166 mmol), 4-methoxyphenylboronic acid (26.2 mg, 0.172 mmol), potassium phosphate (0.052 mL, 0.629 mmol) and palladium tetrakis(triphenylphosphine) (9.5 mg, 8.22 μmol) in N,N-dimethylformamide (2 mL) was pumped under vacuum and backfilled with nitrogen twice, and heated to 90° C. under nitrogen. After 19 h at 90° C., the mixture was concentrated. The residue was purified by preparative TLC (30% ethyl acetate in hexanes, Whatman PARTISEL® PLK5F, Silica Gel 150 A with Fluorescent Indicator, size: 20×20 cm, layer thickness: 1000 μM) to give 4-chloro-6-(4-methoxyphenyl)-2-(4-phenoxyphenyl)nicotinonitrile as white solid (17.5 mg, 26% yield). 1H NMR (400 MHz, CDCl3) δ ppm 8.10 (2H, δ, J=9.04 Hz), 7.99-8.05 (2H, m), 7.76 (1H, s), 7.40 (2H, t, J=7.91 Hz), 7.19 (1H, t, J=7.40 Hz), 7.12 (4H, dd, J=8.16, 4.14 Hz), 7.02 (2H, δ, J=9.03 Hz), 3.89 (3H, s); MS (ES+) m/z: 413 (M+H); LC retention time: 4.488 min (analytical HPLC Method A).

Workup

  1. concentrationthe mixture was concentrated
  2. customThe residue was purified by preparative TLC (30% ethyl acetate in hexanes, Whatman PARTISEL® PLK5F, Silica Gel 150 A with Fluorescent Indicator, size: 20×20 cm, layer thickness: 1000 μM)

Sources & evidence

ORD record
ord-fe7c79fde5d245509045727b8edd8d0e
Source dataset
uspto-grants-2014_09
Patent number
US08846673B2

Reaction notes

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