Ethyl Acetate → N-[(4,6-Dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-6-{4-[(methylamino)sulfonyl]phenyl}-1-(1-methylethyl)-1H-indazole-4-carboxamide

HRID 85519

Reaction equation

HRID 85519 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][NH:28][S:29]([C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1)(=[O:31])=[O:30].C(=O)(O)[O-].[Na+].CCOC(C)=O>COCCOC.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:35]2[CH:34]=[CH:33][C:32]([S:29]([NH:28][CH3:27])(=[O:30])=[O:31])=[CH:37][CH:36]=2)[CH:3]=1)=[O:15]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 441187634-((Methylamino)sulphonyl)benzene boronic acidHCID 545964906-bromo-N-((1,2-dihydro-4,6-dimethyl-2-oxopyridin-3-yl)methyl)-1-isopropyl-1H-indazole-4-carboxamide

Product 1

HCID 68210341N-[(4,6-Dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-6-{4-[(methylamino)sulfonyl]phenyl}-1-(1-methylethyl)-1H-indazole-4-carboxamideYield 55%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 18180031Water 1,2-dimethoxyethaneSolvent

Conditions

Temperature
140 °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 (100 mg, 0.24 mmol), {4-[(methylamino)sulfonyl]phenyl}boronic acid (77 mg, 0.36 mmol) in DME/water (3 mL:1 mL). PdCl2(dppf)-CH2Cl2 (9.8 mg, 0.012 mmol) was added and the resulting mixture was degassed with nitrogen for 10 min. Sodium bicarbonate (60.4 mg, 0.72 mmol) was added, the vessel was sealed, and the insoluble mixture was heated in a microwave at 140° C. for 30 min. EtOAc was added and the solution was filtered thru Celite and evaporated. DCM/MeOH (1:1) was added, it was pre-absorbed on silica gel and purified by SiO2 chromatography (eluent: gradient 100% DCM to 90:10:1 DCM/MeOH/NH4OH). Fractions were evaporated. EtOAc was added along with some hexanes, it was sonicated and the solids that precipitated were filtered, washed with DCM and dried to afford the title compound (67 mg, 54%) as a beige solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.54 (s, 1H) 9.87 (br. s., 1H) 8.62 (t, J=4.80 Hz, 1H) 8.37 (s, 1H) 8.07 (s, 1H) 7.82-7.86 (m, 3H) 7.35 (s, 1H) 7.32 (s, 1H) 5.89 (s, 1H) 5.15 (quin, J=6.63 Hz, 1H) 4.39 (d, J=4.80 Hz, 2H) 3.04 (s, 3H) 2.22 (s, 3H) 2.12 (s, 3H) 1.51 (s, 3H) 1.49 (s, 3H). MS(ES) [M+H]+ 507.9.

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. filtrationthe solution was filtered thru Celite
  5. customevaporated
  6. additionDCM/MeOH (1:1) was added
  7. customit was pre-absorbed on silica gel
  8. custompurified by SiO2 chromatography (eluent: gradient 100% DCM to 90:10:1 DCM/MeOH/NH4OH)
  9. customFractions were evaporated
  10. additionEtOAc was added along with some hexanes, it
  11. customwas sonicated
  12. customthe solids that precipitated
  13. filtrationwere filtered
  14. washwashed with DCM
  15. customdried

Sources & evidence

ORD record
ord-e6787c4b63ff4a53bf016c4535f84adb
Source dataset
uspto-grants-2014_09
Patent number
US08846935B2

Linked notes

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