Sodium Carbonate → Trifluoroacetic acid

HRID 58084Notes

Reaction equation

HRID 58084 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[C:14]3[C:10]=2[CH:11]=[N:12][NH:13]3)O1.I[C:24]1[CH:25]=[CH:26][C:27]([NH2:31])=[N:28][C:29]=1[CH3:30].[C:32](=[O:35])([O-])[O-:33].[Na+].[Na+]>O1CCOCC1.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]>[C:32]([OH:33])([C:18]([F:21])([F:20])[F:19])=[O:35].[CH3:30][C:29]1[N:28]=[C:27]([NH2:31])[CH:26]=[CH:25][C:24]=1[C:9]1[CH:17]=[C:16]([C:18]([F:19])([F:20])[F:21])[CH:15]=[C:14]2[C:10]=1[CH:11]=[N:12][NH:13]2

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 9596135-Iodo-6-methylpyridin-2-amineHCID 897828064-(Tetramethyl-1,3,2-dioxaborolan-2-yl)-6-(trifluoromethyl)-1H-indazole

Product 2

HCID 6422Trifluoroacetic acidHCID 89782892HCID 89782892, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
130 °C

Procedure

To a mixture of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6-(trifluoromethyl)-1H-indazole (0.05 g, 0.160 mmol), 5-iodo-6-methylpyridin-2-amine (0.025 g, 0.107 mmol) and PdCl2(dppf) (0.012 g, 0.016 mmol) in dioxane (1.5 mL) was added 2N sodium carbonate (0.160 mL, 0.320 mmol). The reaction mixture was heated in a microwave reactor at 130° C. for 50 minutes. LCMS showed incomplete conversion of the starting material, so the reaction mixture was heated at 130° C. for an additional 50 minutes. LCMS again showed incomplete conversion. More catalyst was added, and the reaction mixture was again heated at 130° C. for 50 minutes. The reaction mixture was subsequently filtered through a microfiltration frit, which was rinsed with methanol. The solvents were removed in vacuo. The residue was taken up in DMSO and methanol (1:1) and was purified by preparative HPLC, eluting with 25% ACN (containing 0.035% TFA) in H2O (containing 0.05% TFA). The product-containing fractions were dried under vacuum to give a TFA salt of the title compound as a tan film (12 mg, 26%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.32 (s, 3H), 6.94 (d, J=9.35 Hz, 1H), 7.37 (s, 1H), 7.97 (d, J=8.84 Hz, 1H), 8.02 (s, 1H), 8.14 (s, 1H); ESI-MS m/z [M+H]+ calc'd for C14H11F3N4, 293.1. found 293.2.

Workup

  1. temperatureso the reaction mixture was heated at 130° C. for an additional 50 minutes
  2. additionMore catalyst was added
  3. temperaturethe reaction mixture was again heated at 130° C. for 50 minutes
  4. filtrationThe reaction mixture was subsequently filtered through a microfiltration frit, which
  5. washwas rinsed with methanol
  6. customThe solvents were removed in vacuo
  7. custommethanol (1:1) and was purified by preparative HPLC
  8. washeluting with 25% ACN (containing 0.035% TFA) in H2O (containing 0.05% TFA)
  9. customThe product-containing fractions were dried under vacuum

Sources & evidence

ORD record
ord-e54b6e9e7d4b4f5fae9b0d5c5a1d5833
Source dataset
uspto-grants-2016_09
Patent number
US09434743B2

Reaction notes

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