Sodium hydride → {2-[4-(6-Methyl-4-trifluoromethylpyridin-2-yloxy)-phenyl]-ethyl}-thiazolo[5,4-d]pyrimidin-7-ylamine

HRID 1409293Notes

Reaction equation

HRID 1409293 reaction equation
[N:1]1[C:9]2[C:8]([NH:10][CH2:11][CH2:12][C:13]3[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=3)=[N:7][CH:6]=[N:5][C:4]=2[S:3][CH:2]=1.[H-].[Na+].Cl[C:23]1[CH:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[C:25]([CH3:33])[N:24]=1>CN(C=O)C.O>[CH3:33][C:25]1[N:24]=[C:23]([O:19][C:16]2[CH:17]=[CH:18][C:13]([CH2:12][CH2:11][NH:10][C:8]3[C:9]4[N:1]=[CH:2][S:3][C:4]=4[N:5]=[CH:6][N:7]=3)=[CH:14][CH:15]=2)[CH:28]=[C:27]([C:29]([F:32])([F:30])[F:31])[CH:26]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 27366262-Chloro-6-methyl-4-(trifluoromethyl)pyridineHCID 583380364-[2-(Thiazolo[5,4-d]pyrimidin-7-ylamino)-ethyl]-phenol

Product 1

HCID 58338071{2-[4-(6-Methyl-4-trifluoromethylpyridin-2-yloxy)-phenyl]-ethyl}-thiazolo[5,4-d]pyrimidin-7-ylamineYield 22.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

4-[2-(Thiazolo[5,4-d]pyrimidin-7-ylamino)-ethyl]-phenol (0.1 g, 0.37 mmol) was dissolved with magnetic stirring in DMF (1 mL) in a microwave reactor tube, and then treated with NaH (60% dispersion in oil; 13 mg, 0.55 mmol). After bubbling had subsided, 2-chloro-6-methyl-4-trifluoromethylpyridine (86 mg, 0.44 mmol) was added and the reaction mixture was sealed and placed in a CEM Discover® microwave reactor and irradiated for 30 min, with heating to 150° C. After cooling, the reaction mixture was diluted with H2O (5 mL) and partitioned into Et2O (3×10 mL). The pooled organic fractions were diluted with an equal volume of pentane, washed with H2O, dried (Na2SO4) and filtered through a SiO2/Celite plug. The filtrate was concentrated in vacuo to provide a brown wax (126 mg). Prep RP-HPLC purification (CH3CN/H2O eluent; C18 column) afforded {2-[4-(6-methyl-4-trifluoromethylpyridin-2-yloxy)-phenyl]-ethyl}-thiazolo[5,4-d]pyrimidin-7-ylamine (Compound 62; 36 mg) as an off white powder: mp 111-112° C.; 1H NMR (CDCl3) δ 8.76 (s, 1H), 8.55 (s, 1H), 7.31-7.29 (d, J=8.6 Hz, 2H), 7.11-7.07 (m, 3H), 6.83 (s, 1H), 6.22 (br s, 1H), 3.96-3.95 (br m, 2H), 3.05 (t, J=7.2 Hz, 2H), 2.51 (s, 3H); ESIMS m/z 432.2 ([M+H]+).

Workup

  1. customAfter bubbling
  2. customthe reaction mixture was sealed
  3. customirradiated for 30 min
  4. temperatureAfter cooling
  5. custompartitioned into Et2O (3×10 mL)
  6. additionThe pooled organic fractions were diluted with an equal volume of pentane
  7. washwashed with H2O
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered through a SiO2/Celite plug
  10. concentrationThe filtrate was concentrated in vacuo
  11. customto provide a brown wax (126 mg)
  12. customPrep RP-HPLC purification (CH3CN/H2O eluent; C18 column)

Sources & evidence

ORD record
ord-93f7f50161744b00883de580abe11400
Source dataset
uspto-grants-2014_12
Patent number
US08921382B2

Reaction notes

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