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

HRID 2193771노트

반응식

HRID 2193771 반응식
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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매

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온도
110 °C

실험 절차

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)+.

후처리

  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

출처 및 근거

ORD 기록
ord-cc0cd04a63b9406a8232efe44d5969b1
출처 데이터셋
uspto-grants-2012_12
특허 번호
US08329726B2

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