Acetonitrile → Dasatinib monohydrate

HRID 2283517Notes

Reaction equation

HRID 2283517 reaction equation
C(#N)C.Cl[C:5]1[N:10]=[C:9]([CH3:11])[N:8]=[C:7]([NH:12][C:13]2[S:14][C:15]([C:18]([NH:20][C:21]3[C:26]([CH3:27])=[CH:25][CH:24]=[CH:23][C:22]=3[Cl:28])=[O:19])=[CH:16][N:17]=2)[CH:6]=1.[OH:29][CH2:30][CH2:31][N:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1.C(N(CC)CC)C>CCCC[N+](CCCC)(CCCC)CCCC.[Br-].O>[CH3:27][C:26]1[CH:25]=[CH:24][CH:23]=[C:22]([Cl:28])[C:21]=1[NH:20][C:18]([C:15]1[S:14][C:13]([NH:12][C:7]2[CH:6]=[C:5]([N:35]3[CH2:36][CH2:37][N:32]([CH2:31][CH2:30][OH:29])[CH2:33][CH2:34]3)[N:10]=[C:9]([CH3:11])[N:8]=2)=[N:17][CH:16]=1)=[O:19].[OH2:19]

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 76771-(2-Hydroxyethyl)piperazine2×HCID 8471TriethylamineHCID 112694102-[(6-chloro-2-methylpyrimidin-4-yl)amino]-N-(2-chloro-6-methylphenyl)-1,3-thiazole-5-carboxamide

Product 1

HCID 11540687Dasatinib monohydrateYield 179.2%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 962WaterSolvent

Conditions

Temperature
32.5 °C

Procedure

Take 12 ml of acetonitrile in RB flask and charge 1 g of 2-((6-chloro-2-methylpyrimidin-4-yl)amino)-N-(2-chloro-6-methylphenyl)thiazole-5-carboxamide (Formula I), 1.98 g of 1-(2-Hydroxyethyl)piperazine (Formula II), 1.28 g of triethyl amine and 1.02 g of TBAB. Stir the reaction mass for 10-15 min at 30-35° C. Heat the reaction mixture to 75-80° C. and stir for 20-24 h. Check for the completion of reaction with Thin Layer Chromatography (TLC). Charge 4 mL of water slowly and stir the reaction mass for 30-45 mins at 75° C. Cool the reaction mass to 30-35° C. and stir for 2-3 hrs. Filter the reaction mass and wash with acetonitrile and water mixture (1:1). Dry the material to get 1.15 g of crystalline Dasatinib monohydrate.

Workup

  1. temperatureHeat the reaction mixture to 75-80° C.
  2. stirringstir for 20-24 h
  3. customCheck for the completion of reaction with Thin Layer Chromatography (TLC)
  4. stirringstir the reaction mass for 30-45 mins at 75° C
  5. temperatureCool the reaction mass to 30-35° C.
  6. stirringstir for 2-3 hrs
  7. filtrationFilter the reaction mass
  8. washwash with acetonitrile and water mixture (1:1)
  9. customDry the material

Sources & evidence

ORD record
ord-4ce83840b5c341cea0535f611c615099
Source dataset
uspto-grants-2015_09
Patent number
US09145406B2

Reaction notes

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