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

HRID 1711104ノート

反応式

HRID 1711104 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 suspension of 175 (500 mg, 2.00 mmol, scheme 35), 416 (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 degassed for 15 min with nitrogen, and then heated at 110° C. for 22 hrs in a sealed flask [ 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, the filtrate was concentrated and the residue was adsorbed on silica gel and subjected to flash column chromatography (eluents MeOH/CH2Cl2: 2/98 to 10/90). Fractions containing the product were combined, concentrated and treated with AcOEt/hexanes to afford title compound 417 (370 mg, 50% yield) as a yellow-orange solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 9.57 (bs, 1H), 8.45 (d, J=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, J=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). LCMS: 370.0 (M+H)+.

後処理

  1. customwas degassed for 15 min with nitrogen
  2. temperatureAfter cooling to room temperature the reaction mixture
  3. filtrationwas filtered
  4. concentrationthe filtrate was concentrated
  5. additionFractions containing the product
  6. concentrationconcentrated
  7. additiontreated with AcOEt/hexanes

出典と根拠

ORDレコード
ord-9a027e6b434641f1b47e66f73643c2e1
出典データセット
uspto-grants-2010_09
特許番号
US07790729B2

反応ノート

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