Sodium Carbonate → HCID 131735905, compound

HRID 2207395Notes

Reaction equation

HRID 2207395 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(=O)([O-])[O-].[Na+].[Na+].Br[C:35]1[CH:40]=[CH:39][N:38]=[C:37]([F:41])[CH:36]=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:41][C:37]1[CH:36]=[C:35]([C:6]2[CH:5]=[C:4]([NH:17][C:18]3[N:23]=[C:22]([C:24]([F:25])([F:26])[F:27])[CH:21]=[CH:20][N:19]=3)[CH:3]=[C:2]([CH3:1])[CH:7]=2)[CH:40]=[CH:39][N:38]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 27628514-Bromo-2-fluoropyridineHCID 58456089N-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4-(trifluoromethyl)pyrimidin-2-amine

Product 1

HCID 131735905HCID 131735905, compound

Reagents, catalysts & solvents 1

HCID 178418807HCID 178418807, compoundCatalyst

Conditions

Temperature
86 °C

Procedure

A mixture of N-[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (8.00 g, 21.1 mmol), PdCl2(dppf)-dichloromethane adduct (0.861 g, 1.06 mmol), 2-methyl-THF (70.0 mL), 2 M sodium carbonate (21.1 mL, 42.2 mmol), and 4-bromo-2-fluoro pyridine (2.40 mL, 23.2 mmol) was heated to 86° C. for 6 hours under an argon atmosphere. The reaction mixture was directly subjected to an extraction where the aqueous and organic layers were separated. The aqueous layer was extracted with ethyl acetate (50 mL). The combined organic layers were washed sequentially with saturated sodium bicarbonate (40 mL) and saturated aqueous sodium chloride (40 mL). The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was triturated with a mixture of ethyl acetate (15 mL), dichloromethane (5 mL), and methanol (2 mL) to afford N-[3-(2-fluoropyridin-4-yl)-5-methylphenyl]-4-(trifluoromethyl)pyrimidin-2-amine as an off-white solid. MS APCI calc'd for C17H13F4N4 [M+H]+ 349. found 349. 1H NMR (500 MHz, DMSO-d6) δ 10.31 (s, 1H), 8.84 (d, J=4.9 Hz, 1H), 8.30 (d, J=5.3 Hz, 1H), 8.09 (s, 1H), 7.61 (d, J=6.2 Hz, 2H), 7.39 (s, 1H), 7.34 (s, 1H), 7.29 (d, J=4.9 Hz, 1H), 2.36 (s, 3H).

Workup

  1. extractionThe reaction mixture was directly subjected to an extraction where the aqueous and organic layers
  2. customwere separated
  3. extractionThe aqueous layer was extracted with ethyl acetate (50 mL)
  4. washThe combined organic layers were washed sequentially with saturated sodium bicarbonate (40 mL) and saturated aqueous sodium chloride (40 mL)
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude residue was triturated with a mixture of ethyl acetate (15 mL), dichloromethane (5 mL), and methanol (2 mL)

Sources & evidence

ORD record
ord-4b8f6e21aa16485a914172b7781957b2
Source dataset
uspto-grants-2016_06
Patent number
US09376418B2

Reaction notes

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