Potassium Phosphate, Tribasic → N-(2-Fluoro-4-nitrophenyl)-2-(1-methyl-1H-imidazol-4-yl)thieno[3,2-b]pyridin-7-amine

HRID 2193771ノート

反応式

HRID 2193771 の反応式
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:11]3[N:12]=[CH:13][N:14]([CH3:16])[CH:15]=3)[S:10][C:3]=12.[F:17][C:18]1[CH:24]=[C:23]([N+:25]([O-:27])=[O:26])[CH:22]=[CH:21][C:19]=1[NH2:20].C1CCC(P(C2C(C3C=CC=CC=3)=CC=CC=2)C2CCCCC2)CC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:17][C:18]1[CH:24]=[C:23]([N+:25]([O-:27])=[O:26])[CH:22]=[CH:21][C:19]=1[NH:20][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:11]3[N:12]=[CH:13][N:14]([CH3:16])[CH:15]=3)[S:10][C:3]=12

参加物

7

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 1012542-Fluoro-4-nitroanilineHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 594245247-Chloro-2-(1-methyl-1H-imidazol-4-yl)thieno[3,2-b]pyridine

生成物 1

HCID 59457676N-(2-Fluoro-4-nitrophenyl)-2-(1-methyl-1H-imidazol-4-yl)thieno[3,2-b]pyridin-7-amine収率 50.1%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 1140Toluene溶媒

反応条件

温度
110 °C

実験手順

A stirred suspension of 10 (500 mg, 2.00 mmol), 337 (406 mg, 2.60 mmol), Pd2(dba)3 (73 mg, 0.08 mmol), (2-biphenyl)dicyclohexylphosphine (56 mg, 0.16 mmol), and K3PO4 (638 mg, 3.00 mmol) in toluene (20 ml) was degased for 15 min with nitrogen at room temperature, and then heated in a sealed flask at 110° C. for 22 hrs (J. P. Wolfe, H. Tomori, J. P. Sadighi. J. Yin. S. L. Buchwald J. Org. Chem. 2000, 65, 1158-1174). After cooling to room temperature the reaction mixture was filtered, rinsed with toluene, concentrated and adsorbed on silica gel. The crude product was purified by flash column chromatography (eluents MeOH/CH2Cl2: 2/98 to 10/90) and precipitated in AcOEt/hexanes to afford title compound 338 (370 mg, 50% yield) as a yellow-orange solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 9.57 (bs, 1H), 8.45 (d, 5.1 Hz, 1H), 8.22 (dd, J=11.3, 2.5 Hz, 1H), 8.06 (dd. J=8.9, 2.3 Hz, 1H), 7.83 (d, I=1.2 Hz, 1H), 7.70 (d, J=1.2 Hz, 1H), 7.63 (s, 1H), 7.24 (t, J=8.7 Hz, 1H), 6.94 (bd, J=4.7 Hz, 1H), 3.71 (s, 3H). MS (m/z): 370.0 (M+H)+.

後処理

  1. customwas degased for 15 min with nitrogen at room temperature
  2. temperatureAfter cooling to room temperature the reaction mixture
  3. filtrationwas filtered
  4. washrinsed with toluene
  5. concentrationconcentrated
  6. customThe crude product was purified by flash column chromatography (eluents MeOH/CH2Cl2: 2/98 to 10/90)
  7. customprecipitated in AcOEt/hexanes

出典と根拠

ORDレコード
ord-cc0cd04a63b9406a8232efe44d5969b1
出典データセット
uspto-grants-2012_12
特許番号
US08329726B2

反応ノート

読み込み中…