Potassium Carbonate → 4-(3-(1-(7-Chloroquinazolin-2-YL)azetidin-3-YL)pyrazin-2-YL)-2-fluoro-N-methylbenzamide

HRID 624530Notes

Reaction equation

HRID 624530 reaction equation
FC(F)(F)C(O)=O.FC(F)(F)C(O)=O.FC(F)(F)C(O)=O.[NH:22]1[CH2:25][CH:24]([C:26]2[C:27]([C:32]3[CH:41]=[CH:40][C:35]([C:36]([NH:38][CH3:39])=[O:37])=[C:34]([F:42])[CH:33]=3)=[N:28][CH:29]=[CH:30][N:31]=2)[CH2:23]1.Cl[C:44]1[N:53]=[CH:52][C:51]2[C:46](=[CH:47][C:48]([Cl:54])=[CH:49][CH:50]=2)[N:45]=1.C(=O)([O-])[O-].[K+].[K+]>C(O)CCC.O>[Cl:54][C:48]1[CH:47]=[C:46]2[C:51]([CH:52]=[N:53][C:44]([N:22]3[CH2:23][CH:24]([C:26]4[C:27]([C:32]5[CH:41]=[CH:40][C:35]([C:36]([NH:38][CH3:39])=[O:37])=[C:34]([F:42])[CH:33]=5)=[N:28][CH:29]=[CH:30][N:31]=4)[CH2:25]3)=[N:45]2)=[CH:50][CH:49]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 124139292,7-DichloroquinazolineHCID 867054064-(3-(Azetidin-3-YL)pyrazin-2-YL)-2-fluoro-N-methylbenzamide tris(2,2,2-trifluoroacetate)

Product 1

HCID 727148524-(3-(1-(7-Chloroquinazolin-2-YL)azetidin-3-YL)pyrazin-2-YL)-2-fluoro-N-methylbenzamideYield 92.3%

Reagents, catalysts & solvents 2

HCID 2631-ButanolSolventHCID 962WaterSolvent

Conditions

Temperature
110 °C

Procedure

4-(3-(Azetidin-3-yl)pyrazin-2-yl)-2-fluoro-N-methylbenzamide tris(2,2,2-trifluoroacetate) (0.150 g, 0.239 mmol), 2,7-dichloroquinazoline (0.062 g, 0.310 mmol), and potassium carbonate (0.165 g, 1.19 mmol, Aldrich) were mixed in butan-1-ol (2 mL) in a sealed tube. The reaction mixture was stirred at 110° C. for 18 h. The reaction mixture was cooled to room temperature, diluted with water, and extracted with EtOAc. The organic layer was separated, washed with saturated sodium chloride, dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting crude mixture was purified via silica gel flash column chromatography eluting with 50% to 100% EtOAc in hexanes to yield give 99 mg (92%) of a light yellow solid. 1H NMR (400 MHz, chloroFORM-d) δ ppm 3.09 (d, J=4.50 Hz, 3 H) 4.29-4.38 (m, 1 H) 4.46-4.58 (m, 4 H) 6.75-6.85 (br. m., 1 H) 7.18 (dd, J=8.61, 1.56 Hz, 1 H) 7.36 (d, J=12.32 Hz, 1 H) 7.40 (dd, J=8.12, 1.27 Hz, 1 H) 7.60 (d, J=8.41 Hz, 1 H) 7.63 (br. s., 1 H) 8.27 (t, J=8.02 Hz, 1 H) 8.57 (d, J=2.15 Hz, 1 H) 8.65 (d, J=2.15 Hz, 1 H) 8.97 (s, 1 H). m/z=449 (M+1).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionextracted with EtOAc
  3. customThe organic layer was separated
  4. washwashed with saturated sodium chloride
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe resulting crude mixture was purified via silica gel flash column chromatography
  9. washeluting with 50% to 100% EtOAc in hexanes
  10. customto yield

Sources & evidence

ORD record
ord-246e60ab0f7d421695077e09d1843c49
Source dataset
uspto-grants-2016_04
Patent number
US09303028B2

Reaction notes

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