Tris(hydroxymethyl)aminomethane → Dasatinib

HRID 517620Notes

Reaction equation

HRID 517620 reaction equation
[OH:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1.C(=O)([O-])[O-].[Na+].[Na+].C(OC(=O)[N:22]([C:39]1[CH:44]=[C:43](Cl)[N:42]=[C:41]([CH3:46])[N:40]=1)[C:23]1[S:24][C:25]([C:28](=[O:38])[NH:29][C:30]2[C:35]([CH3:36])=[CH:34][CH:33]=[CH:32][C:31]=2[Cl:37])=[CH:26][N:27]=1)(C)(C)C.C(NC(C)(C)C)(C)(C)C.C(O)C(N)(CO)CO>O.CS(C)=O>[CH3:36][C:35]1[C:30]([NH:29][C:28]([C:25]2[S:24][C:23]([NH:22][C:39]3[CH:44]=[C:43]([N:7]4[CH2:8][CH2:9][N:4]([CH2:3][CH2:2][OH:1])[CH2:5][CH2:6]4)[N:42]=[C:41]([CH3:46])[N:40]=3)=[N:27][CH:26]=2)=[O:38])=[C:31]([Cl:37])[CH:32]=[CH:33][CH:34]=1

Participants

8

Reactant 5

HCID 6503Tris(hydroxymethyl)aminomethaneHCID 76771-(2-Hydroxyethyl)piperazineHCID 10340Sodium CarbonateHCID 30889N-(1,1-Dimethylethyl)-2-methyl-2-propanamineHCID 118319272Ter-butyl-6-chloro-2-methylpyrimidin-4-yl-(5-(2-chloro-6-methylphenylcarbamoyl)thiazol-2-yl)carbamate

Product 1

HCID 3062316DasatinibYield 80%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

In a reaction flask 283.5 ml dimethylsulfoxide, 29.83 g 1-(2-hydroxyethyl)piperazine (0.229 mol), 12.08 g sodium carbonate (0.144 mol), 56.70 g ter-butyl-6-chloro-2-methylpyrimidin-4-yl-(5-(2-chloro-6-methylphenylcarbamoyl)thiazol-2-yl)carbamate (0.114 mol) were charged at a temperature of about 25° C. and the reaction mixture was kept under these conditions for about five hours. At the end of the reaction, 760 ml water were added, the mixture was kept under stirring for about 30 minutes and the formed solid was filtered, washed with water (4×260 ml) and suspended in 440 ml methanol. 42.88 g di-terbutylamine (DBTA, 0.120 mol) were added, the temperature was brought to the solvent reflux value and 15.19 g tromethamol (TRIZMA) (0.125 mol) were added. The temperature was brought to about 25° C. and the formed solid was filtered, washed with methanol (2×45 ml) and dried in oven under vacuum at a temperature of about 50° C. for eight hours to give 44.51 g dasatinib.

Workup

  1. additionwere added
  2. filtrationthe formed solid was filtered
  3. washwashed with water (4×260 ml)
  4. additionwere added
  5. customwas brought to about 25° C.
  6. filtrationthe formed solid was filtered
  7. washwashed with methanol (2×45 ml)
  8. customdried in oven under vacuum at a temperature of about 50° C. for eight hours

Sources & evidence

ORD record
ord-c4f4af90af56498897ad91723b599f4a
Source dataset
uspto-grants-2015_08
Patent number
US09115124B1

Reaction notes

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