Sodium Bicarbonate → Trifluoroacetic acid

HRID 58086Notes

Reaction equation

HRID 58086 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.Br[C:24]1[CH:25]=[CH:26][C:27]([NH:31][S:32]([CH3:35])(=[O:34])=[O:33])=[N:28][C:29]=1[CH3:30].[C:36]([O-:39])(O)=[O:37].[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:36]([OH:39])([C:18]([F:21])([F:20])[F:19])=[O:37].[CH3:30][C:29]1[N:28]=[C:27]([NH:31][S:32]([CH3:35])(=[O:34])=[O:33])[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 516892Sodium BicarbonateHCID 79049128N-(5-bromo-6-methylpyridin-2-yl)methanesulfonamideHCID 897828064-(Tetramethyl-1,3,2-dioxaborolan-2-yl)-6-(trifluoromethyl)-1H-indazole

Product 2

HCID 6422Trifluoroacetic acidHCID 89782825N-(6-methyl-5-(6-(trifluoromethyl)-1H-indazol-4-yl)pyridin-2-yl)methanesulfonamide

Reagents, catalysts & solvents 2

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

Conditions

Temperature
140 °C

Procedure

A vial was charged with a mixture of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6-(trifluoromethyl)-1H-indazole (0.1 g, 0.320 mmol), N-(5-bromo-6-methylpyridin-2-yl)methanesulfonamide (0.170 g, 0.641 mmol) and PdCl2(dppf) (0.012 g, 0.016 mmol) in dioxane (8 mL) and aqueous saturated NaHCO3 (2 mL). The resulting light brown suspension was heated at 140° C. for 45 minutes in a microwave reactor. The reaction mixture was subsequently concentrated and the crude residue was purified by preparative HPLC, eluting with 30% ACN (containing 0.035% TFA) in H2O (containing 0.05% TFA) over a period of 8 minutes. The product-containing fractions were combined and the volatiles were removed in vacuo to give a TFA salt of the title compound as an off white solid (0.039 g, 33%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.30 (s, 3H), 3.31 (br s, 3H), 7.02 (d, J=8.08 Hz, 1H), 7.32 (d, J=1.01 Hz, 1H), 7.76 (d, J=8.34 Hz, 1H), 7.97 (s, 1H), 8.02 (s, 1H); ESI-MS m/z [M+H]+ calc'd for C15H13F3N4O2S, 371.1. found 371.17.

Workup

  1. concentrationThe reaction mixture was subsequently concentrated
  2. customthe crude residue was purified by preparative HPLC
  3. washeluting with 30% ACN (containing 0.035% TFA) in H2O (containing 0.05% TFA) over a period of 8 minutes
  4. customthe volatiles were removed in vacuo

Sources & evidence

ORD record
ord-cd6fe5c4ce0f45a498f3c1504b160037
Source dataset
uspto-grants-2016_09
Patent number
US09434743B2

Reaction notes

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