Sodium Carbonate → HCID 86674327, compound

HRID 1028139Notes

Reaction equation

HRID 1028139 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[N:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[CH:20][N:19]=2)[CH:5]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:7]=1.[C:28](=[O:31])([O-])[O-:29].[Na+].[Na+].Br[C:35]1[N:36]=[C:37]([N:40]2[CH2:45][CH2:44][O:43][CH2:42][CH2:41]2)[S:38][CH:39]=1>>[F:25][C:24]([F:27])([F:26])[C:28]([OH:29])=[O:31].[CH3:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[N:23]=[C:22]([C:24]([F:26])([F:25])[F:27])[CH:21]=[CH:20][N:19]=2)[CH:5]=[C:6]([C:35]2[N:36]=[C:37]([N:40]3[CH2:45][CH2:44][O:43][CH2:42][CH2:41]3)[S:38][CH:39]=2)[CH:7]=1

Participants

4

Reactant 3

HCID 10340Sodium CarbonateHCID 438110424-(4-Bromo-1,3-thiazol-2-yl)morpholineHCID 58456089N-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4-(trifluoromethyl)pyrimidin-2-amine

Product 1

HCID 86674327HCID 86674327, compoundYield 28%

Conditions

Temperature
80 °C

Procedure

N-[3-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4-(trifluoromethyl)-pyrimidin-2-amine (100 mg, 0.264 mmol), sodium carbonate (33.5 mg, 0.316 mmol), 4-(4-bromo-1,3-thiazol-2-yl)morpholine (79 mg, 0.316 mmol), 2-(dicyclohexylphosphino)-3,6-dimethoxy-2′-4′-6′-tri-1-propyl-1,1′-biphenyl (7.1 mg, 0.01 mmol) and chloro[2-(dicyclohexylphosphino)-3,6-dimethoxy-2′-4′-6′-tri-1-propyl-1,1′-biphenyl][2-(2-aminoethyl)phenyl]palladium(II) (10.5 mg, 0.013 mmol) were placed in a 4-mL vial. The vial was evacuated and back-filled with nitrogen (3×). 1,4-Dioxane (2 mL) and water (0.4 mL) were added and the reaction mixture heated to 80° C. for 16 hours. The reaction mixture was cooled to room temperature and filtered over celite with methanol (˜20 mL). Solvent evaporation gave a crude residue which was purified by preparative HPLC Reverse phase (C-18), eluting with acetonitrile/water+0.1% trifluoroacetic acid (eluting with 40-100% MeCN), to give 20 mg (0.037 mmol, 14.2% yield) of N-{3-methyl-5-[2-(morpholin-4-yl)-1,3-thiazol-4-yl]phenyl}-4-(trifluoromethyl)pyrimidin-2-amine trifluoroacetate salt as a yellow solid. MS APCI [M+H]+ m/z 422.1. 1H NMR (500 MHz, d6-DMSO): 2.30 (s, 3H), 3.43 (t, J=4.9 Hz, 4H), 3.72 (t, J=4.9 Hz, 4H), 7.14 (s, 1H), 7.23 (d, J=4.9 Hz, 1H), 7.33 (s, 1H), 7.40 (s, 1H), 8.17 (s, 1H), 8.79 (d, J=4.9 Hz, 1H).

Workup

  1. customThe vial was evacuated
  2. additionback-filled with nitrogen (3×)
  3. addition1,4-Dioxane (2 mL) and water (0.4 mL) were added
  4. temperatureThe reaction mixture was cooled to room temperature
  5. filtrationfiltered over celite with methanol (˜20 mL)
  6. customSolvent evaporation
  7. customgave a crude residue which
  8. customwas purified by preparative HPLC Reverse phase (C-18)
  9. washeluting with acetonitrile/water+0.1% trifluoroacetic acid (eluting with 40-100% MeCN)

Sources & evidence

ORD record
ord-40b7ff1e8e6143e6a0e26360ff0c9001
Source dataset
uspto-grants-2014_05
Patent number
US08735417B2

Reaction notes

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