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

HRID 607151Notes

Reaction equation

HRID 607151 reaction equation
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

Participants

8

Reactant 5

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

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)+.

Workup

  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

Sources & evidence

ORD record
ord-799c33d979f348fd99b1fff6b705becb
Source dataset
uspto-grants-2011_03
Patent number
US07915411B2

Reaction notes

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