Water → 4-(3-(1-(7-Chloro-6-fluoroquinazolin-2-yl)azetidin-3-yl)pyrazin-2-yl)-2-fluoro-N-methylbenzamide

HRID 624533Notes

Reaction equation

HRID 624533 reaction equation
Cl[C:2]1[N:11]=[CH:10][C:9]2[C:4](=[CH:5][C:6]([Cl:13])=[C:7]([F:12])[CH:8]=2)[N:3]=1.FC(F)(F)C(O)=O.FC(F)(F)C(O)=O.FC(F)(F)C(O)=O.[NH:35]1[CH2:38][CH:37]([C:39]2[C:40]([C:45]3[CH:54]=[CH:53][C:48]([C:49]([NH:51][CH3:52])=[O:50])=[C:47]([F:55])[CH:46]=3)=[N:41][CH:42]=[CH:43][N:44]=2)[CH2:36]1.C(=O)([O-])[O-].[K+].[K+].O>CS(C)=O>[Cl:13][C:6]1[CH:5]=[C:4]2[C:9]([CH:10]=[N:11][C:2]([N:35]3[CH2:36][CH:37]([C:39]4[C:40]([C:45]5[CH:54]=[CH:53][C:48]([C:49]([NH:51][CH3:52])=[O:50])=[C:47]([F:55])[CH:46]=5)=[N:41][CH:42]=[CH:43][N:44]=4)[CH2:38]3)=[N:3]2)=[CH:8][C:7]=1[F:12]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 867054064-(3-(Azetidin-3-YL)pyrazin-2-YL)-2-fluoro-N-methylbenzamide tris(2,2,2-trifluoroacetate)HCID 867054082,7-Dichloro-6-fluoroquinazoline

Product 1

HCID 727148544-(3-(1-(7-Chloro-6-fluoroquinazolin-2-yl)azetidin-3-yl)pyrazin-2-yl)-2-fluoro-N-methylbenzamideYield 70.4%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2,7-dichloro-6-fluoroquinazoline (46 mg, 0.21 mmol), 4-(3-(azetidin-3-yl)pyrazin-2-yl)-2-fluoro-N-methylbenzamide tris(2,2,2-trifluoroacetate) (0.15 g, 0.23 mmol), and potassium carbonate (0.15 g, 1.06 mmol) in DMSO (1 mL) was heated to 100° C. for 1 h, then cooled to RT. Water was added, then the product was extracted into EtOAc. The combined extracts were washed with water (2×), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo to give an oil. This oil was purified by silica gel chromtography to give 4-(3-(1-(7-Chloro-6-fluoroquinazolin-2-yl)azetidin-3-yl)pyrazin-2-yl)-2-fluoro-N-methylbenzamide as a light yellow solid (69 mg, 70% yield). m/z=467 (M+1). 1H NMR (400 MHz, chloroFORM-d) δ ppm 3.09 (d, J=4.70 Hz, 3 H) 4.28-4.38 (m, 1 H) 4.45-4.54 (m, 4 H) 6.80 (br. s., 1 H) 7.32-7.42 (m, 3 H) 7.71 (d, J=6.65 Hz, 1 H) 8.27 (t, J=7.92 Hz, 1 H) 8.58 (d, J=1.76 Hz, 1 H) 8.65 (s, 1 H) 8.94 (s, 1 H).

Workup

  1. temperaturecooled to RT
  2. extractionthe product was extracted into EtOAc
  3. washThe combined extracts were washed with water (2×)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give an oil
  8. customThis oil was purified by silica gel chromtography

Sources & evidence

ORD record
ord-79b88d8520fb4ec7ad18878f2282d66f
Source dataset
uspto-grants-2016_04
Patent number
US09303028B2

Reaction notes

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