1-(2-Hydroxyethyl)piperazine → Dasatinib

HRID 515259Notes

Reaction equation

HRID 515259 reaction equation
[OH:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1.Br[C:11]1[N:16]=[C:15]([CH3:17])[N:14]=[C:13]([NH:18][C:19]2[S:20][C:21]([C:24]([NH:26][C:27]3[C:32]([CH3:33])=[CH:31][CH:30]=[CH:29][C:28]=3[Cl:34])=[O:25])=[CH:22][N:23]=2)[CH:12]=1.CCN(C(C)C)C(C)C>C(O)CCC>[CH3:33][C:32]1[C:27]([NH:26][C:24]([C:21]2[S:20][C:19]([NH:18][C:13]3[CH:12]=[C:11]([N:7]4[CH2:8][CH2:9][N:4]([CH2:3][CH2:2][OH:1])[CH2:5][CH2:6]4)[N:16]=[C:15]([CH3:17])[N:14]=3)=[N:23][CH:22]=2)=[O:25])=[C:28]([Cl:34])[CH:29]=[CH:30][CH:31]=1

Participants

5

Reactant 3

HCID 76771-(2-Hydroxyethyl)piperazine2×HCID 81531DiisopropylethylamineHCID 866764302-(6-bromo-2-methylpyrimidin-4-ylamino)-N-(2-chloro-6-methylphenyl)thiazole-5-formamide2×

Product 1

HCID 3062316DasatinibYield 87.9%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

1-(2-hydroxyethyl)piperazine (Compound 3) (65 g, 0.5 mol), 2-(6-bromo-2-methylpyrimidin-4-ylamino)-N-(2-chloro-6-methylphenyl)thiazole-5-formamide (Compound 14) (43.9 g, 0.1 mol), n-butanol (670 mL) and DIPEA (28.3 g, 0.2 mol) were mixed in reaction flask and reacted by refluxing for 7 h. After the reactant was cooled down to room temperature, crystals precipitated overnight. After air pump filtration, the cake was rinsed with n-butanol (500 mL) by stirring for 30 min. Then filtrated and the cake was dried to give white solid target Compound 1 (42.9 g, yield: 87.9%).

Workup

  1. customreacted
  2. temperatureby refluxing for 7 h
  3. customcrystals precipitated overnight
  4. filtrationAfter air pump filtration
  5. washthe cake was rinsed with n-butanol (500 mL)
  6. filtrationThen filtrated
  7. customthe cake was dried

Sources & evidence

ORD record
ord-da4a7745794e47c9bddd73a90632e2ab
Source dataset
uspto-grants-2015_08
Patent number
US09108954B2

Reaction notes

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