Potassium Carbonate → Thiazolo[5,4-d]pyrimidin-7-yl-{2-[4-(4-trifluoromethylpyridin-3-yloxy)-phenyl]-ethyl}-amine

HRID 1409294Notes

Reaction equation

HRID 1409294 reaction equation
[F:1][C:2]([F:20])([F:19])[C:3]1[CH:8]=[CH:7][N:6]=[CH:5][C:4]=1[O:9][C:10]1[CH:15]=[CH:14][C:13]([CH2:16][CH2:17][NH2:18])=[CH:12][CH:11]=1.Cl[C:22]1[C:23]2[N:30]=[CH:29][S:28][C:24]=2[N:25]=[CH:26][N:27]=1.C([O-])([O-])=O.[K+].[K+]>CS(C)=O>[N:30]1[C:23]2[C:22]([NH:18][CH2:17][CH2:16][C:13]3[CH:12]=[CH:11][C:10]([O:9][C:4]4[CH:5]=[N:6][CH:7]=[CH:8][C:3]=4[C:2]([F:19])([F:1])[F:20])=[CH:15][CH:14]=3)=[N:27][CH:26]=[N:25][C:24]=2[S:28][CH:29]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 2630077-Chlorothiazolo[5,4-D]pyrimidineHCID 583380352-[4-(4-Trifluoromethylpyridin-3-yloxy)-phenyl]-ethylamine

Product 1

HCID 58338012Thiazolo[5,4-d]pyrimidin-7-yl-{2-[4-(4-trifluoromethylpyridin-3-yloxy)-phenyl]-ethyl}-amineYield 73.5%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

2-[4-(4-Trifluoromethylpyridin-3-yloxy)-phenyl]-ethylamine (0.25 g, 0.88 mmol), 7-chlorothiazolo[5,4-d]pyrimidine (0.15 g, 0.88 mmol) and K2CO3 (3 g) were dissolved with magnetic stirring in DMSO (7 mL) in a 25 mL round bottom flask equipped with a dry nitrogen line at 25° C. After placing the flask in a sonication bath for 3 min, the reaction mixture was heated on a steam bath for 2 min. The mixture was filtered, and the filter cake was washed with acetone. The combined filtrates were diluted with 0.15 N HCl (100 mL) and washed successively with Et2O (2×50 mL) and EtOAc (2×50 mL). The pooled organic fractions were filtered and concentrated in vacuo to provide 0.27 g of a yellow gum. The gum was dissolved in a small volume of EtOAc and passed through a short SiO2 column with 1% MeOH/EtOAc as eluent. The appropriate fractions were pooled and concentrated in vacuo to provide a clear colorless oil (0.17 g). Trituration in Et2O followed by decanting of the solvent afforded thiazolo[5,4-d]pyrimidin-7-yl-{2-[4-(4-trifluoromethylpyridin-3-yloxy)-phenyl]-ethyl}-amine (Compound 43; 170 mg) as a yellow solid: mp 83-87° C.; 1H NMR (400 MHz, CDCl3) δ 8.77 (s, 1H), 8.55 (s, 1H), 8.50 (s, 1H), 8.34 (s, 1H), 7.54 (s, 1H), 7.30 (d, J=8.6 Hz, 2H), 7.06-6.99 (m, 2H), 6.22 (s, 1H), 3.94 (dd, J=12.9, 6.5 Hz, 2H), 3.04 (t, J=7.1 Hz, 2H); ESIMS m/z 418.2 ([M+H]+).

Workup

  1. customequipped with a dry nitrogen line at 25° C
  2. customfor 3 min
  3. temperaturethe reaction mixture was heated on a steam bath for 2 min
  4. filtrationThe mixture was filtered
  5. washthe filter cake was washed with acetone
  6. additionThe combined filtrates were diluted with 0.15 N HCl (100 mL)
  7. washwashed successively with Et2O (2×50 mL) and EtOAc (2×50 mL)
  8. filtrationThe pooled organic fractions were filtered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8e413e215c25432090b54e882dcb3abc
Source dataset
uspto-grants-2014_12
Patent number
US08921382B2

Reaction notes

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