Nitrogen → 7-Cyclobutyl-5-(8-fluoro-2-phenyl-quinolin-7-yl)-imidazo[5,1-f][1,2,4]triazin-4-ylamine

HRID 386206ノート

反応式

HRID 386206 の反応式
[CH:1]1([C:5]2[N:13]3[C:8]([C:9]([NH2:14])=[N:10][CH:11]=[N:12]3)=[C:7](I)[N:6]=2)[CH2:4][CH2:3][CH2:2]1.[F:16][C:17]1[C:18](B2OC(C)(C)C(C)(C)O2)=[CH:19][CH:20]=[C:21]2[C:26]=1[N:25]=[C:24]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH:23]=[CH:22]2.C(=O)([O-])[O-].[Cs+].[Cs+].N#N.C(=O)(O)[O-].[Na+]>C(COC)OC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:1]1([C:5]2[N:13]3[C:8]([C:9]([NH2:14])=[N:10][CH:11]=[N:12]3)=[C:7]([C:18]3[C:17]([F:16])=[C:26]4[C:21]([CH:22]=[CH:23][C:24]([C:27]5[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=5)=[N:25]4)=[CH:20][CH:19]=3)[N:6]=2)[CH2:4][CH2:3][CH2:2]1

参加物

9

反応物 5

HCID 947NitrogenHCID 10796Cesium carbonateHCID 516892Sodium BicarbonateHCID 533286247-Cyclobutyl-5-iodo-imidazo[5,1-f][1,2,4]triazin-4-ylamineHCID 536290468-Fluoro-2-phenyl-7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)quinoline

生成物 1

HCID 117185057-Cyclobutyl-5-(8-fluoro-2-phenyl-quinolin-7-yl)-imidazo[5,1-f][1,2,4]triazin-4-ylamine

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
75 °C

実験手順

A stirred solution of 7-cyclobutyl-5-iodo-imidazo[5,1-f][1,2,4]triazin-4-ylamine (40 mg, 0.1 mmol), 8-fluoro-2-phenyl-7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)quinoline (52 mg, 0.15 mmol) and cesium carbonate (50 mg, 0.15 mmol) in dimethoxyethane (DME) (1.67 mL) and H2O (0.33 mL) was degassed for 10 minutes using N2. Tetrakis(triphenylphosphine)palladium(0) (7 mg, 0.006 mmol) was added, and the reaction was heated to 75° C. and maintained at this temperature for 16 hours. After cooling, the reaction mixture was poured into saturated sodium bicarbonate (NaHCO3) solution (50 ml) and extracted with EtOAc (3×50 ml). The combined organics were washed with brine (2×50 ml), dried over magnesium sulfate (MgSO4), filtered and concentrated. The material was purified by chromatography on silica gel [eluting with 100% DCM→0.4% MeOH in DCM] resulting in the title compound as a white solid; 1H NMR (CDCl3, 400 MHz) δ 2.06-1.99 (m, 1H), 2.10-2.20 (m, 1H), 2.42-2.52 (m, 2H), 2.62-2.71 (m, 2H), 4.14-4.21 (m, 1H), 7.45-7.56 (m, 3H), 7.74 (d, J=8.6 Hz, 1H), 7.79 (dd, J=6.3 Hz, 6.3 Hz, 1H), 7.87 (s, 1H), 7.99 (d, J=8.8 Hz, 1H), 8.21 (d, J=6.8 Hz, 2H), 8.27 (d, J=7.6 Hz, 1H); MS (ES+): m/z 411.00 (100) [MH+], HPLC: tR=3.53 min (MicromassZQ, polar—5 min).

後処理

  1. temperaturemaintained at this temperature for 16 hours
  2. temperatureAfter cooling
  3. extractionextracted with EtOAc (3×50 ml)
  4. washThe combined organics were washed with brine (2×50 ml)
  5. dry with materialdried over magnesium sulfate (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe material was purified by chromatography on silica gel [eluting with 100% DCM→0.4% MeOH in DCM]

出典と根拠

ORDレコード
ord-eb999f8411394705bb8019399d91c816
出典データセット
uspto-grants-2013_02
特許番号
US08367826B2

反応ノート

読み込み中…