Dimethylacetamide → HCID 66926956, compound

HRID 81037Notes

Reaction equation

HRID 81037 reaction equation
Cl[C:2]1[C:3]([Cl:23])=[C:4]([C:7]([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)=[CH:8][N:9]=1)[C:5]#[N:6].[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)C>C(OCC)(=O)C.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:23][C:3]1[C:2]([C:29]2[CH:30]=[CH:31][C:26]([O:25][CH3:24])=[CH:27][CH:28]=2)=[N:9][CH:8]=[C:7]([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)[C:4]=1[C:5]#[N:6]

Participants

7

Reactant 4

HCID 31374DimethylacetamideHCID 62657Potassium Phosphate, TribasicHCID 201262(4-Methoxyphenyl)boronic acidHCID 866656862,3-Dichloro-5-(4-phenoxyphenyl)isonicotinonitrile

Product 1

HCID 66926956HCID 66926956, compoundYield 55.2%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 2,3-dichloro-5-(4-phenoxyphenyl)isonicotinonitrile (109 mg, 0.319 mmol), 4-methoxyphenylboronic acid (58.3 mg, 0.383 mmol), potassium phosphate (136 mg, 0.639 mmol) and palladium tetrakis(triphenylphosphine) (18.46 mg, 0.016 mmol) was pumped and backfilled with nitrogen 3 times. N,N-Dimethylacetamide (2 mL) was added. The mixture was again pumped and backfilled with nitrogen 3 times. The reaction tube was sealed and heated to 150° C. under microwave for 30 min. The mixture was diluted with ethyl acetate (30 mL), washed with 1:1 mixture of brine and water (15 mL), brine (15 mL), dried (MgSO4) and concentrated. Silica gel chromatography, loading with toluene and eluting with 5-30% ethyl acetate in hexanes, gave 3-chloro-2-(4-methoxyphenyl)-5-(4-phenoxyphenyl)isonicotinonitrile (72.7 mg, 52% yield). 1H NMR (500 MHz, CDCl3) δ ppm 8.75 (1H, s), 7.74-7.83 (2H, m), 7.56-7.64 (2H, m), 7.37-7.47 (2H, m), 7.21 (1H, t, J=7.42 Hz), 7.09-7.18 (4H, m), 7.00-7.09 (2H, m), 3.90 (3H, s); MS (ES+) m/z: 413 (M+H); LC retention time: 4.810 min (analytical HPLC Method A).

Workup

  1. customThe reaction tube was sealed
  2. washwashed with 1:1 mixture of brine and water (15 mL), brine (15 mL)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. washeluting with 5-30% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-450d83c637d54df59c404805231f818b
Source dataset
uspto-grants-2014_09
Patent number
US08846673B2

Reaction notes

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