Water → N-Methyl-N-[1-methyl-4-(2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-1H-pyrazol-3-yl]-methanesulfonamide

HRID 1262329Notes

Reaction equation

HRID 1262329 reaction equation
Br[C:2]1[N:10]2[C:5]([CH:6]=[N:7][C:8]([S:11][CH3:12])=[N:9]2)=[CH:4][CH:3]=1.[CH3:13][N:14]([C:19]1[C:23](B2OC(C)(C)C(C)(C)O2)=[CH:22][N:21]([CH3:33])[N:20]=1)[S:15]([CH3:18])(=[O:17])=[O:16].CN(C)C=O.O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+].O>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:13][N:14]([C:19]1[C:23]([C:2]2[N:10]3[C:5]([CH:6]=[N:7][C:8]([S:11][CH3:12])=[N:9]3)=[CH:4][CH:3]=2)=[CH:22][N:21]([CH3:33])[N:20]=1)[S:15]([CH3:18])(=[O:16])=[O:17]

Participants

8

Reactant 6

HCID 962WaterHCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 57416040N-Methyl-N-[1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-3-yl]methanesulfonamideHCID 574161287-Bromo-2-(methylsulfanyl)pyrrolo[2,1-f][1,2,4]triazine

Product 1

HCID 66711859N-Methyl-N-[1-methyl-4-(2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-1H-pyrazol-3-yl]-methanesulfonamideYield 38.1%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
95 °C

Procedure

Into a 1-Neck round-bottom flask, 7-Bromo-2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazine (0.580 g, 2.38 mmol), N-Methyl-N-[1-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazol-3-yl]-methanesulfonamide (1.50 g, 4.75 mmol), Tetrakis(triphenylphosphine)palladium(0) (0.274 g, 0.238 mmol), N,N-Dimethylformamide (10 mL, 100 mmol), 1,4-Dioxane (20 mL, 200 mmol), and 1.50 M of Sodium carbonate in Water (9.50 mL, 14.2 mmol) were added. The reaction mixture was heated at 95° C. overnight. The solvent was removed under vacuum. The reaction was partitioned with water and DCM. The organic was separated, washed with Brine and dried over Na2SO4. The solid was filtered and washed with DCM. The solvent was removed under vacuum to give a solid. The reaction mixture was purified via ISCO column chromatography with DCM and methanol as eluant (0 to 5% methanol). The collected fractions afforded N-Methyl-N-[1-methyl-4-(2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-1H-pyrazol-3-yl]-methanesulfonamide as a yellow solid (0.32 g, 38%) 1256f. Into a 8-dram vial, Methylene chloride (10 mL, 200 mmol), N-Methyl-N-[1-methyl-4-(2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-1H-pyrazol-3-yl]-methanesulfonamide (0.250 g, 0.709 mmol), and m-CPBA 70-75% (70:30, m-Chloroperbenzoic acid:3-Chlorobenzoic acid, 0.175 g, 0.709 mmol) were added. The reaction mixture was stirred at room temperature for one hour. Sat. NaHCo3 and DCM was added. The organic was separated, washed with Brine and dried over Na2SO4. The solid was filtered and washed with DCM. The solvent was removed under vacuum to afford a yellow solid.

Workup

  1. customThe solvent was removed under vacuum
  2. customThe reaction was partitioned with water and DCM
  3. customThe organic was separated
  4. washwashed with Brine
  5. dry with materialdried over Na2SO4
  6. filtrationThe solid was filtered
  7. washwashed with DCM
  8. customThe solvent was removed under vacuum
  9. customto give a solid
  10. customThe reaction mixture was purified via ISCO column chromatography with DCM and methanol as eluant (0 to 5% methanol)

Sources & evidence

ORD record
ord-dcb126d8e89a4fbd94bd9cf0f6edfb50
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

Loading…