Hydrochloric Acid → Methyl Hydroxyethyl Piperazinyl Methyl Pyrimidinylamino Thiazolecarboxylate

HRID 515246Notes

Reaction equation

HRID 515246 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([N:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][OH:17])[CH2:11][CH2:10]2)[CH:3]=1.[NH2:18][C:19]1[S:20][C:21]([C:24]([O:26][CH3:27])=[O:25])=[CH:22][N:23]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.Cl>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[OH:17][CH2:16][CH2:15][N:12]1[CH2:13][CH2:14][N:9]([C:4]2[N:5]=[C:6]([CH3:8])[N:7]=[C:2]([NH:18][C:19]3[S:20][C:21]([C:24]([O:26][CH3:27])=[O:25])=[CH:22][N:23]=3)[CH:3]=2)[CH2:10][CH2:11]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 238005Methyl 2-aminothiazole-5-carboxylate2×HCID 634876Binap, (A+-)-HCID 144795582-(4-(6-Chloro-2-methylpyrimidin-4-yl)piperazin-1-yl)ethanol2×

Product 1

HCID 49821888Methyl Hydroxyethyl Piperazinyl Methyl Pyrimidinylamino ThiazolecarboxylateYield 75.3%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Procedure

2-(4-(6-chloro-2-methylpyrimidin-4-yl)piperazin-1-yl)ethanol (Compound 4) (25.7 g, 0.1 mol), methyl 2-aminothiazole-5-formate (Compound 5) (18.9 g, 0.12 mol), cesium carbonate (45.6 g, 0.14 mol), palladium acetate (2.2 g, 0.01 mol) and BINAP (6.2 g, 0.01 mol) were mixed with toluene (1100 mL) in reaction flask, and heated by stirring to reflux for 16 h. The reactant was cooled and 2 mol/L hydrochloric acid was added and stirred for 10 mins. After vacuum filtration the filtrate was phase-separated and the aqueous phase was extracted by toluene (500 mL). The separated aqueous phase was neutralized by NaOH solution (6 mol/L) at 10-15° C., and then grew the grains for 1 h. After vacuum filtration the cake was rinsed by water to give yellow solid target Compound 6 (28.5 g, yield: 75.2%).

Workup

  1. temperatureheated
  2. temperatureto reflux for 16 h
  3. temperatureThe reactant was cooled
  4. stirringstirred for 10 mins
  5. filtrationAfter vacuum filtration the filtrate
  6. customwas phase-separated
  7. extractionthe aqueous phase was extracted by toluene (500 mL)
  8. customwas neutralized by NaOH solution (6 mol/L) at 10-15° C.
  9. customfor 1 h
  10. filtrationAfter vacuum filtration the cake
  11. washwas rinsed by water

Sources & evidence

ORD record
ord-4c7f379581124faea8f9d7096b64a957
Source dataset
uspto-grants-2015_08
Patent number
US09108954B2

Reaction notes

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