Sodium Carbonate → HCID 131735891, compound

HRID 2207365Notes

Reaction equation

HRID 2207365 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].Br[C:8]1[CH:9]=[CH:10][C:11]([F:14])=[N:12][CH:13]=1.[CH3:15][C:16]1[CH:17]=[C:18]([NH:31][C:32]2[N:37]=[C:36]([C:38]([F:41])([F:40])[F:39])[CH:35]=[CH:34][N:33]=2)[CH:19]=[C:20](B2OC(C)(C)C(C)(C)O2)[CH:21]=1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].ClCCl>[F:14][C:11]1[N:12]=[CH:13][C:8]([C:20]2[CH:19]=[C:18]([NH:31][C:32]3[N:37]=[C:36]([C:38]([F:40])([F:41])[F:39])[CH:35]=[CH:34][N:33]=3)[CH:17]=[C:16]([CH3:15])[CH:21]=2)=[CH:9][CH:10]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 27831685-Bromo-2-fluoropyridine2×HCID 58456089N-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4-(trifluoromethyl)pyrimidin-2-amine

Product 1

HCID 131735891HCID 131735891, compound

Reagents, catalysts & solvents 1

HCID 178418807HCID 178418807, compoundCatalyst2×

Conditions

Temperature
85 °C

Procedure

2-Methyl-THF (123 mL), sodium carbonate (2M, 18.5 mL, 36.9 mmol) and 5-bromo-2-fluoropyridine (7.15 g, 40.6 mmol) were added to N-[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (14 g, 36.9 mmol) and the reaction mixture was purged and flushed with Ar(g) (3×) before adding PdCl2(dppf)-dichloromethane adduct (1.51 g, 1.85 mmol). The reaction mixture was heated to 85° C. overnight. Another portion of 5-bromo-2-fluoropyridine (2.00 g) and PdCl2(dppf)-dichloromethane adduct (300 mg, 0.368 mmol) were added to the reaction mixture and heated to 85° C. overnight. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. A hot solution of 10% water, 20% DCM and 70% MeCN was added to the residue and the product was collected by filtration. The product was washed with cold DCM to yield N-[3-(6-fluoropyridin-3-yl)-5-methylphenyl]-4-(trifluoromethyl)pyrimidin-2-amine as a green-tinted solid. MS APC calc'd for C17H13F3N4 [M+H]+ 349. found 349. 1H NMR (500 MHz, DMSO-d6) δ 10.27 (s, 1H), 8.82 (d, J=4.8 Hz, 1H), 8.45 (s, 1H), 8.18 (td, J=2.4 Hz, 8.2 Hz, 1H), 7.93 (s, 1H), 7.56 (s, 1H), 7.31-7.24 (m, 2H), 7.18 (s, 1H), 3.32 (s, 3H).

Workup

  1. customthe reaction mixture was purged
  2. customflushed with Ar(g) (3×)
  3. temperatureheated to 85° C. overnight
  4. temperatureThe reaction mixture was cooled to room temperature
  5. concentrationconcentrated under reduced pressure
  6. additionA hot solution of 10% water, 20% DCM and 70% MeCN was added to the residue
  7. filtrationthe product was collected by filtration
  8. washThe product was washed with cold DCM

Sources & evidence

ORD record
ord-204b57084d574ae2baf184ac1769734a
Source dataset
uspto-grants-2016_06
Patent number
US09376418B2

Reaction notes

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