Potassium Fluoride → HCID 58456408, compound

HRID 1039870Notes

Reaction equation

HRID 1039870 reaction equation
C(P(C12CC3CC(CC(C3)C1)C2)C12CC3CC(CC(C3)C1)C2)CCC.[Br:26][C:27]1[CH:28]=[C:29]([NH:42][C:43]2[N:48]=[C:47]([C:49]([F:52])([F:51])[F:50])[CH:46]=[CH:45][N:44]=2)[CH:30]=[C:31](B2OC(C)(C)C(C)(C)O2)[CH:32]=1.Br[C:54]1[S:58][CH:57]=[N:56][CH:55]=1.[F-].[K+]>C1COCC1.CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2].O>[Br:26][C:27]1[CH:28]=[C:29]([NH:42][C:43]2[N:48]=[C:47]([C:49]([F:50])([F:51])[F:52])[CH:46]=[CH:45][N:44]=2)[CH:30]=[C:31]([C:54]2[S:58][CH:57]=[N:56][CH:55]=2)[CH:32]=1

Participants

9

Reactant 4

HCID 522689Potassium FluorideHCID 5460595-BromothiazoleHCID 11371790Bis(adamantan-1-yl)(butyl)phosphaneHCID 58456329N-[3-bromo-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine

Product 1

HCID 58456408HCID 58456408, compoundYield 66%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
75 °C

Procedure

A solution of Pd(OAc)2 (19 mg, 0.085 mmol) and butyl di-1-adamantyl phosphine (61 mg, 0.18 mmol) in THF (12.8 mL) was stirred for 15 min. Intermediate 10 (755 mg, 1.70 mmol), 5-bromo-1,3-thiazole (760 μL, 8.50 mmol), potassium fluoride (296 mg, 5.10 mmol), and water (4.25 mL) were then added, and the mixture was heated to 75° C. overnight. After cooling to rt, the mixture was diluted with 100 mL EtOAc and washed with 100 mL brine. A bright yellow solid remained undissolved on the walls of the separatory funnel, which was thus rinsed with 100 mL THF. The combined organic extracts were dried (Na2SO4) and concentrated in vacuo. Purification by Chromatography on silica gel (40 g; dry load; 100:0 to 50:50 hexanes:EtOAc over 25 minutes) provided N-[3-bromo-5-(1,3-thiazol-5-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (449 mg, 1.12 mmol, 66%) as an off-white solid. MS APCI: [M+H]+ m/z 403.0. 1H NMR (400 MHz, (CD3)2CO): δ 9.46 (s, 1H); 9.03 (s, 1H); 8.89 (d, J=4.9 Hz, 1H); 8.32-8.26 (m, 2H); 8.16 (s, 1H); 7.59 (s, 1H); 7.33 (d, J=4.9 Hz, 1H). rhSYK activity=++

Workup

  1. temperatureAfter cooling to rt
  2. washwashed with 100 mL brine
  3. washwas thus rinsed with 100 mL THF
  4. dry with materialThe combined organic extracts were dried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customPurification by Chromatography on silica gel (40 g; dry load; 100:0 to 50:50 hexanes:EtOAc over 25 minutes)

Sources & evidence

ORD record
ord-ae6079f745894634bde479f84dcfa847
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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