Aniline → N-(4-(4-methyl-2-(2-propylthiazolo[5,4-b]pyridin-7-ylamino)phenylthio)phenyl)acetamide

HRID 607151ノート

反応式

HRID 607151 の反応式
C(N1CCN2CCN(CC(C)C)P1N(CC(C)C)CC2)C(C)C.CC(C)([O-])C.[Na+].Cl[C:31]1[CH:36]=[CH:35][N:34]=[C:33]2[S:37][C:38]([CH2:40][CH2:41][CH3:42])=[N:39][C:32]=12.[NH2:43][C:44]1[CH:49]=[C:48]([CH3:50])[CH:47]=[CH:46][C:45]=1[S:51][C:52]1[CH:57]=[CH:56][C:55]([NH:58][C:59](=[O:61])[CH3:60])=[CH:54][CH:53]=1.NC1C=CC=CC=1>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]>[CH3:50][C:48]1[CH:47]=[CH:46][C:45]([S:51][C:52]2[CH:53]=[CH:54][C:55]([NH:58][C:59](=[O:61])[CH3:60])=[CH:56][CH:57]=2)=[C:44]([NH:43][C:31]2[CH:36]=[CH:35][N:34]=[C:33]3[S:37][C:38]([CH2:40][CH2:41][CH3:42])=[N:39][C:32]=23)[CH:49]=1

参加物

8

反応物 5

HCID 6115AnilineHCID 45712432,8,9-Triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo(3.3.3)undecane2 回HCID 23676156Sodium t-butoxideHCID 43168935N-[4-(2-Amino-4-methyl-phenylsulfanyl)-phenyl]-acetamideHCID 668084877-Chloro-2-propyl-thiazolo[5,4-b]pyridine

生成物 1

HCID 60204753N-(4-(4-methyl-2-(2-propylthiazolo[5,4-b]pyridin-7-ylamino)phenylthio)phenyl)acetamide収率 12.1%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒2 回HCID 1140Toluene溶媒

反応条件

温度
100 °C

実験手順

A dry nitrogen-purged flask was charged with 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phospha-bicyclo[3.3.3]undecane (38.6 mg, 0.1128 mmol), tris(dibenzylideneacetone)-dipalladium (25.8 mg, 0.0282 mmol), and sodium tert-butoxide (83.8 mg, 0.8463 mmol). A solution of the product of Example 5G (120 mg, 0.5642 mmol) in anhydrous toluene (5 mL) was added via syringe, followed by the product from Example 7b (130 mg, 0.4773 mmol). The reaction was heated in a preheated 100° C. oil bath for 2.5 hours, cooled to room temperature, treated with additional 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phospha-bicyclo[3.3.3]undecane (38.6 mg), tris(dibenzylideneacetone)dipalladium (25.8 mg) and starting aniline (130 mg), and heated at 100° C. for an additional 18 hours. The reaction was cooled to room temperature and the solvent removed by rotary evaporation in vacuo. Purification by silica gel flash chromatography with a gradient of 40% to 60% ethyl acetate/methylene chloride gave the desired title compound as a tan foam (26 mg, 10%). 1H NMR (300 MHz, DMSO-d6) δ ppm: 1.01 (t, J=7.35 Hz, 3H) 1.73-1.91 (m, 2H) 2.01 (s, 3H) 2.34 (s, 3H) 3.07 (t, J=7.54 Hz, 2H) 6.78 (d, J=5.52 Hz, 1H) 6.97-7.09 (m, 1H) 7.16-7.30 (m, 3H) 7.36 (s, 1H) 7.51 (d, J=8.82 Hz, 2H) 8.15 (d, J=5.52 Hz, 1H) 8.53 (s, 1H) 9.99 (s, 1H); MS (DCI/NH3) m/z 449 (M+H)+.

後処理

  1. customA dry nitrogen-purged flask
  2. temperaturecooled to room temperature
  3. temperatureheated at 100° C. for an additional 18 hours
  4. temperatureThe reaction was cooled to room temperature
  5. customthe solvent removed by rotary evaporation in vacuo
  6. customPurification by silica gel flash chromatography with a gradient of 40% to 60% ethyl acetate/methylene chloride

出典と根拠

ORDレコード
ord-799c33d979f348fd99b1fff6b705becb
出典データセット
uspto-grants-2011_03
特許番号
US07915411B2

反応ノート

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