Acetic Acid → 4-(2-methyl-6-(2-(methylsulfonyl)ethyl)pyridin-3-yl)-6-(trifluoromethyl)-1H-indazole

HRID 58112Notes

Reaction equation

HRID 58112 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH3:8])[C:5]([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)=[CH:4][CH:3]=1.CCN([CH2:27][CH3:28])CC.[CH3:29][S:30]([O-:32])=[O:31].[Na+].C(O)(=O)C>CC(O)C.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]>[CH3:8][C:6]1[C:5]([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)=[CH:4][CH:3]=[C:2]([CH2:28][CH2:27][S:30]([CH3:29])(=[O:32])=[O:31])[N:7]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 8471TriethylamineHCID 2733271Sodium methanesulfinateHCID 897832784-(6-chloro-2-methylpyridin-3-yl)-6-(trifluoromethyl)-1H-indazole

Product 1

HCID 897832254-(2-methyl-6-(2-(methylsulfonyl)ethyl)pyridin-3-yl)-6-(trifluoromethyl)-1H-indazoleYield 47.3%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 3776IsopropanolSolvent

Conditions

Temperature
100 °C

Procedure

To a microwave vial were added of 4-(6-chloro-2-methylpyridin-3-yl)-6-(trifluoromethyl)-1H-indazole (0.33 g, 1.059 mmol), potassium vinyl trifluoroborate (0.312 g, 2.329 mmol), Et3N (0.298 mL, 2.117 mmol) and PdCl2(dppf) (0.077 g, 0.106 mmol) in IPA (12 mL) to give a light-brown suspension. The mixture was bubbled with nitrogen and heated at 100° C. for 30 minutes in a microwave reactor. Sodium methanesulfinate (0.540 g, 5.29 mmol) and acetic acid (0.606 mL, 10.59 mmol) were added and the reaction mixture was stirred at 60° C. for 18 hours and then cooled. The volatiles were evaporated, and the resulting crude residue was purified by LCMS, eluting with 40% ACN in H2O (containing 10 mM NH4HCO3) over a period of 8 minutes. The product-containing fractions were combined and the volatiles were evaporated using a GeneVac™ to give the title compound as white solid (0.192 g, 47.3%). 1H NMR (400 MHz, CD3OD) δ ppm 2.41 (s, 3H), 3.05 (s, 3H), 3.35-3.43 (m, 2H), 3.59-3.72 (m, 2H), 7.32 (s, 1H), 7.40 (d, J=7.83 Hz, 1H), 7.75 (d, J=7.83 Hz, 1H), 7.89 (s, 1H), 7.98 (s, 1H); ESI-MS m/z [M+H]+ calc'd for C17H16F3N3O2S, 384.1. found 384.09.

Workup

  1. customto give a light-brown suspension
  2. customThe mixture was bubbled with nitrogen
  3. temperaturecooled
  4. customThe volatiles were evaporated
  5. customthe resulting crude residue was purified by LCMS
  6. washeluting with 40% ACN in H2O (containing 10 mM NH4HCO3) over a period of 8 minutes
  7. customthe volatiles were evaporated

Sources & evidence

ORD record
ord-20ea0102c140423b996e800852d7f7b3
Source dataset
uspto-grants-2016_09
Patent number
US09434743B2

Reaction notes

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