Dimethylacetamide → 3-Chloro-5-(naphthalen-2-yl)isonicotinonitrile

HRID 81026

反応式

HRID 81026 の反応式
Cl[C:2]1[CH:9]=[N:8][CH:7]=[C:6]([Cl:10])[C:3]=1[C:4]#[N:5].[CH:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[CH:13][C:12]=1B(O)O.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:10][C:6]1[CH:7]=[N:8][CH:9]=[C:2]([C:13]2[CH:12]=[CH:11][C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[CH:14]=2)[C:3]=1[C:4]#[N:5]

参加物

7

反応物 4

HCID 31374DimethylacetamideHCID 62657Potassium Phosphate, TribasicHCID 2734375(Naphthalen-2-yl)boronic acidHCID 111375993,5-Dichloropyridine-4-carbonitrile

生成物 1

HCID 669273763-Chloro-5-(naphthalen-2-yl)isonicotinonitrile収率 52.4%

試薬・触媒・溶媒 2

HCID 11979704Tetrakis(triphenylphosphine)palladium触媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
150 °C

実験手順

A mixture of 3,5-dichloroisonicotinonitrile (0.300 g, 1.734 mmol), naphthalen-2-ylboronic acid (0.328 g, 1.908 mmol), potassium phosphate (0.736 g, 3.47 mmol) and palladium tetrakis(triphenylphosphine) (0.100 g, 0.087 mmol) was pumped and backfilled with nitrogen 3 times. N,N-Dimethylacetamide (6 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 (80 mL), washed with 1:1 mixture of brine and water (30 mL), brine (30 mL), dried (MgSO4) and concentrated. Silica gel chromatography, loading with toluene and eluting with 10-35% ethyl acetate in hexanes, gave 3-chloro-5-(naphthalen-2-yl)isonicotinonitrile as a white solid (240.5 mg, 46% yield). 1H NMR (400 MHz, CDCl3) δ ppm 8.83 (1H, s), 8.81 (1H, s), 8.00-8.15 (2H, m), 7.87-8.00 (2H, m), 7.67 (1H, dd, J=8.53, 2.01 Hz), 7.53-7.64 (2H, m); MS (ES+) m/z: 265 (M+H); LC retention time: 4.066 min (analytical HPLC Method A).

後処理

  1. customThe reaction tube was sealed
  2. washwashed with 1:1 mixture of brine and water (30 mL), brine (30 mL)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. washeluting with 10-35% ethyl acetate in hexanes

出典と根拠

ORDレコード
ord-06c61ee85e754176bc66261b89a58240
出典データセット
uspto-grants-2014_09
特許番号
US08846673B2

関連ノート

読み込み中…