Water → 1-cyclopentyl-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-6-(4-fluorophenyl)-1H-indazole-4-carboxamide

HRID 85463Notes

Reaction equation

HRID 85463 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:16]([NH:18][CH2:19][C:20]2[C:21](=[O:28])[NH:22][C:23]([CH3:27])=[CH:24][C:25]=2[CH3:26])=[O:17])[C:5]2[CH:6]=[N:7][N:8]([CH:11]3[CH2:15][CH2:14][CH2:13][CH2:12]3)[C:9]=2[CH:10]=1.[F:29][C:30]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=1.C(=O)(O)[O-].[Na+].O>O1CCOCC1.O.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(Cl)Cl>[CH:11]1([N:8]2[C:9]3[CH:10]=[C:2]([C:33]4[CH:34]=[CH:35][C:30]([F:29])=[CH:31][CH:32]=4)[CH:3]=[C:4]([C:16]([NH:18][CH2:19][C:20]4[C:21](=[O:28])[NH:22][C:23]([CH3:27])=[CH:24][C:25]=4[CH3:26])=[O:17])[C:5]=3[CH:6]=[N:7]2)[CH2:15][CH2:14][CH2:13][CH2:12]1

Participants

7

Reactant 4

HCID 962WaterHCID 2856454-Fluorophenylboronic acidHCID 516892Sodium BicarbonateHCID 545970746-bromo-1-cyclopentyl-N-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-1H-indazole-4-carboxamide

Product 1

HCID 545971531-cyclopentyl-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-6-(4-fluorophenyl)-1H-indazole-4-carboxamideYield 75%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
100 °C

Procedure

In a 25 mL sealable tube under nitrogen were combined 6-bromo-1-cyclopentyl-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1H-indazole-4-carboxamide (100 mg, 0.23 mmol) and (4-fluorophenyl)boronic acid (47.3 mg, 0.34 mmol) in dioxane/water (3 mL:1 mL). PdCl2(dppf)-CH2Cl2 adduct (9.2 mg, 0.011 mmol) was added and the resulting mixture was degassed with nitrogen for 10 min. Sodium bicarbonate (56.8 mg, 0.68 mmol) was added, the vessel was sealed, and the insoluble mixture was heated in a microwave at 100° C. for 20 min. Upon cooling down, water was added, and solids that crashed out were filtered. DCM/MeOH (1:1) was added, the contents pre-absorbed on silica gel and purified by SiO2 chromatography (eluent: gradient 0 to 80:20:2 DCM/MeOH/NH4OH). The collected product was suspended in EtOAc along with some hexanes. The mixture was sonicated, and the solids that precipitated were filtered and dried to afford the title compound as a light grey solid (78 mg, 75%). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.54 (s, 1H) 8.64 (t, J=4.80 Hz, 1H) 8.37 (s, 1H) 8.13 (s, 1H) 7.89-7.94 (m, 2H) 7.85 (s, 1H) 7.35 (t, J=8.97 Hz, 2H) 5.89 (s, 1H) 5.34 (quin, J=7.14 Hz, 1H) 4.40 (br. s., 1H) 4.38 (br. s., 1H) 2.22 (s, 3H) 2.11-2.18 (m, 5H) 1.98-2.06 (m, 2H) 1.86-1.94 (m, 2H) 1.66-1.75 (m, 2H). LC-MS (ES) m/z=459.1

Workup

  1. customIn a 25 mL sealable tube under nitrogen were combined
  2. customthe resulting mixture was degassed with nitrogen for 10 min
  3. customthe vessel was sealed
  4. temperatureUpon cooling down
  5. filtrationsolids that crashed out were filtered
  6. additionDCM/MeOH (1:1) was added
  7. customthe contents pre-absorbed on silica gel
  8. custompurified by SiO2 chromatography (eluent: gradient 0 to 80:20:2 DCM/MeOH/NH4OH)
  9. customThe mixture was sonicated
  10. customthe solids that precipitated
  11. filtrationwere filtered
  12. customdried

Sources & evidence

ORD record
ord-47e548a61aa141ff91ca9edc77e3b96f
Source dataset
uspto-grants-2014_09
Patent number
US08846935B2

Reaction notes

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