2,8,9-Triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo(3.3.3)undecane → (5-Methyl-2-phenylsulfanyl-phenyl)-(2-propyl-thiazolo[5,4-b]pyridin-7-yl)-amine

HRID 607145노트

반응식

HRID 607145 반응식
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.[CH3:43][C:44]1[CH:45]=[CH:46][C:47]([S:51][C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)=[C:48]([NH2:50])[CH:49]=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]>[CH3:43][C:44]1[CH:45]=[CH:46][C:47]([S:51][C:52]2[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=2)=[C:48]([NH:50][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

참가 물질

7

반응물 4

HCID 45712432,8,9-Triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo(3.3.3)undecaneHCID 23676156Sodium t-butoxideHCID 433496035-Methyl-2-phenylsulfanyl-phenylamineHCID 668084877-Chloro-2-propyl-thiazolo[5,4-b]pyridine

생성물 1

HCID 25010669(5-Methyl-2-phenylsulfanyl-phenyl)-(2-propyl-thiazolo[5,4-b]pyridin-7-yl)-amine수율 15%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매2회HCID 1140Toluene용매2회

실험 절차

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 mg, 0.111 mmol), tris(dibenzylideneacetone)-dipalladium (25.4 mg, 0.0277 mmol), and sodium tert-butoxide (82.4 mg, 0.8322 mmol). A solution of the product of Example 5G (118 mg, 0.5548 mmol) in anhydrous toluene (2 mL) and a solution of the product from Example 5I (107.5 mg, 0.4993 mmol) in toluene (3 mL) were added via syringe. The reaction was heated at reflux in a preheated 120° oil bath for 18 hours, cooled to room temperature, treated with additional tris(dibenzylideneacetone)dipalladium (25.4 mg), and heated at reflux for an additional 2.5 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 1% to 3% ethyl acetate/methylene chloride afforded the title compound (29 mg, 0.074 mmol, 15%). 1H NMR (300 MHz, DMSO-D6) δ ppm: 1.00 (t, J=7.35 Hz, 3H) 1.71-1.90 (m, 2H) 2.38 (s, 3H) 3.05 (t, J=7.35 Hz, 2H) 6.87 (d, J=5.52 Hz, 1H) 7.07 (dd, J=7.91, 1.29 Hz, 1H) 7.12-7.31 (m, 5H) 7.37-7.46 (m, 2H) 8.15 (d, J=5.52 Hz, 1H) 8.52 (s, 1H); MS (DCI/NH3) m/z 392 (M+H)+.

후처리

  1. customA dry nitrogen-purged flask
  2. temperatureThe reaction was heated
  3. temperatureat reflux in a preheated 120° oil bath for 18 hours
  4. temperatureheated
  5. temperatureat reflux for an additional 2.5 hours
  6. temperatureThe reaction was cooled to room temperature
  7. customthe solvent removed by rotary evaporation in vacuo
  8. customPurification by silica gel flash chromatography with a gradient of 1% to 3% ethyl acetate/methylene chloride

출처 및 근거

ORD 기록
ord-7777c1da0e174038b1a6a0c600b63552
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07915411B2

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