Sodium Bicarbonate → ethyl 2-(4-(6-(trifluoromethyl)-1H-indazol-4-yl)-1H-pyrazol-1-yl)acetate

HRID 58087Notes

Reaction equation

HRID 58087 reaction equation
Br[C:2]1[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][NH:6]2.CC1(C)C(C)(C)OB([C:23]2[CH:24]=[N:25][N:26]([CH2:28][C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH:27]=2)O1.[C:35]([O-:38])(O)=[O:36].[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:35]([OH:38])([C:11]([F:14])([F:13])[F:12])=[O:36].[F:12][C:11]([F:14])([F:13])[C:9]1[CH:8]=[C:7]2[C:3]([CH:4]=[N:5][NH:6]2)=[C:2]([C:23]2[CH:24]=[N:25][N:26]([CH2:28][C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH:27]=2)[CH:10]=1

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 162183851-(Ethoxycarbonylmethyl)-1H-pyrazole-4-boronic acid pinacol esterHCID 247292324-Bromo-6-(trifluoromethyl)-1H-indazole

Product 2

HCID 6422Trifluoroacetic acidHCID 117772858ethyl 2-(4-(6-(trifluoromethyl)-1H-indazol-4-yl)-1H-pyrazol-1-yl)acetateYield 37%

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-bromo-6-(trifluoromethyl)-1H-indazole (0.3 g, 1.132 mmol), ethyl 2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)acetate (0.349 g, 1.245 mmol) and PdCl2(dppf) (0.041 g, 0.057 mmol) in dioxane (10 mL) and aqueous saturated NaHCO3 (3 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 a gradient of 40-45% ACN (containing 0.035% TFA) in H2O (containing 0.05% TFA) over a period of 6.5 minutes. The product-containing fractions were combined and the volatiles were removed via rotary evaporation to give a TFA salt of the title compound as a light brown solid (0.14 g, 37%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.24 (t, J=7.07 Hz, 3H), 4.19 (q, J=7.16 Hz, 2H), 5.15 (s, 2H), 7.60 (d, J=1.01 Hz, 1H), 7.77 (s, 1H), 8.27 (d, J=0.76 Hz, 1H), 8.53 (s, 1H), 8.63 (s, 1H), 13.64 (s, 1H); ESI-MS m/z [M+H]+ calc'd for C15H13F3N4O2, 339.1. found 339.

Workup

  1. concentrationThe reaction mixture was subsequently concentrated
  2. customthe crude residue was purified by preparative HPLC
  3. washeluting with a gradient of 40-45% ACN (containing 0.035% TFA) in H2O (containing 0.05% TFA) over a period of 6.5 minutes
  4. customthe volatiles were removed via rotary evaporation

Sources & evidence

ORD record
ord-c1065c26471d4e4e96f5075fe410f072
Source dataset
uspto-grants-2016_09
Patent number
US09434743B2

Reaction notes

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