Sodium Bicarbonate → N-[(4,6-Dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-6-(2-methylphenyl)-1H-indazole-4-carboxamide

HRID 1476491Notes

Reaction equation

HRID 1476491 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:14]([NH:16][CH2:17][C:18]2[C:19](=[O:26])[NH:20][C:21]([CH3:25])=[CH:22][C:23]=2[CH3:24])=[O:15])[C:5]2[CH:6]=[N:7][N:8]([CH:11]([CH3:13])[CH3:12])[C:9]=2[CH:10]=1.[CH3:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1B(O)O.C(=O)(O)[O-].[Na+].C(Cl)Cl.CO>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>[CH3:24][C:23]1[CH:22]=[C:21]([CH3:25])[NH:20][C:19](=[O:26])[C:18]=1[CH2:17][NH:16][C:14]([C:4]1[C:5]2[CH:6]=[N:7][N:8]([CH:11]([CH3:13])[CH3:12])[C:9]=2[CH:10]=[C:2]([C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=2[CH3:27])[CH:3]=1)=[O:15]

Participants

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 27332672-Methylphenyl boronic acidHCID 21226129Dichloromethane methanolHCID 545964906-bromo-N-((1,2-dihydro-4,6-dimethyl-2-oxopyridin-3-yl)methyl)-1-isopropyl-1H-indazole-4-carboxamide

Product 1

HCID 68210252N-[(4,6-Dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-6-(2-methylphenyl)-1H-indazole-4-carboxamideYield 67.6%

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-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-indazole-4-carboxamide (120 mg, 0.29 mmol) and [(2-methylphenyl)boronic acid (58.6 mg, 0.43 mmol) in dioxane/water (3 mL:1 mL). PdCl2(dppf)-CH2Cl2 (11.74 mg, 0.014 mmol) was added and the resulting mixture was degassed with nitrogen for 10 min. Sodium bicarbonate (72.5 mg, 0.86 mmol) was added and the insoluble mixture was heated in a microwave at 100° C. for 15 min. DCM/MeOH (1:1) was added, it was pre-absorbed on silica gel and purified by SiO2 chromatography (eluent: gradient 100% DCM to 80:20:2 DCM/MeOH/NH4OH). Fractions were evaporated. EtOAc was added along with some hexanes, it was sonicated and the solids that precipitated were filtered and dried to afford the title compound (84 mg, 66%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.51 (s, 1H) 8.55 (t, J=4.80 Hz, 1H) 8.41 (s, 1H) 7.80 (s, 1H) 7.55 (d, J=1.01 Hz, 1H) 7.27-7.35 (m, 4H) 5.87 (s, 1H) 5.09 (quin, J=6.57 Hz, 1H) 4.36 (d, J=5.05 Hz, 2H) 2.26 (s, 3H) 2.20 (s, 3H) 2.11 (s, 3H) 1.49 (s, 3H) 1.47 (s, 3H). MS (ES) [M+H]+ 429.1.

Workup

  1. customIn a 25 mL sealable tube under nitrogen were combined
  2. customthe resulting mixture was degassed with nitrogen for 10 min
  3. customit was pre-absorbed on silica gel
  4. custompurified by SiO2 chromatography (eluent: gradient 100% DCM to 80:20:2 DCM/MeOH/NH4OH)
  5. customFractions were evaporated
  6. additionEtOAc was added along with some hexanes, it
  7. customwas sonicated
  8. customthe solids that precipitated
  9. filtrationwere filtered
  10. customdried

Sources & evidence

ORD record
ord-c642ff8c643f4628888dfd243467881f
Source dataset
uspto-grants-2015_04
Patent number
US09018382B2

Reaction notes

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