Sodium Carbonate → HCID 118092560, compound

HRID 2207355Notes

Reaction equation

HRID 2207355 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.Br[C:29]1[CH:30]=[CH:31][C:32]([C:35]([OH:37])=[O:36])=[N:33][CH:34]=1.C(=O)([O-])[O-].[Na+].[Na+]>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>[CH3:1][C:2]1[CH:7]=[C:6]([C:29]2[CH:30]=[CH:31][C:32]([C:35]([OH:37])=[O:36])=[N:33][CH:34]=2)[CH:5]=[C:4]([NH:17][C:18]2[N:23]=[C:22]([C:24]([F:27])([F:25])[F:26])[CH:21]=[CH:20][N:19]=2)[CH:3]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 6085445-Bromopyridine-2-carboxylic acidHCID 58456089N-(3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4-(trifluoromethyl)pyrimidin-2-amine

Product 1

HCID 118092560HCID 118092560, compound

Reagents, catalysts & solvents 1

HCID 178418807HCID 178418807, compoundCatalyst

Conditions

Temperature
130 °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 (6.5 g, 17.1 mmol), 5-bromopyridine-2-carboxylic acid (3.92 g, 19.4 mmol), aqueous sodium carbonate (2M, 17.1 mL, 34.3 mmol) in dioxanes (57.1 mL) was flushed and purged with Ar(g) (3×). PdCl2(dppf)-dichloromethane adduct (646 mg, 0.791 mmol) was then added to the reaction mixture and heated at 130° C. for 10 hours. Upon cooling, the reaction mixture was filtered through a CELITE pad and washed with dioxane. The crude reaction mixture was concentrated under reduced pressure and diluted with 90% MeCN and 10% 2M HCl (aq). The crude solid was isolated by filtration and was recrystallized from dichloromethane to yield 5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridine-2-carboxylic acid as an off-white powder. MS APC calc'd for C18H14F3N4O2 [M+H]+ 375. found 375. 1H NMR (500 MHz, DMSO-d6) δ 10.32 (s, 1H), 8.95 (s, 1H), 8.84 (d, J=5.4, 1H), 8.18 (d, J=9.6, 1H), 8.12 (d, J=9.3, 1H), 8.05 (s, 1H), 7.28 (s, 2H), 2.38 (s, 3H).

Workup

  1. customwas flushed
  2. custompurged with Ar(g) (3×)
  3. temperatureUpon cooling
  4. filtrationthe reaction mixture was filtered through a CELITE pad
  5. washwashed with dioxane
  6. customThe crude reaction mixture
  7. concentrationwas concentrated under reduced pressure
  8. additiondiluted with 90% MeCN and 10% 2M HCl (aq)
  9. customThe crude solid was isolated by filtration
  10. customwas recrystallized from dichloromethane

Sources & evidence

ORD record
ord-e9307689ea9043729bddd5e7b9d7786d
Source dataset
uspto-grants-2016_06
Patent number
US09376418B2

Reaction notes

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