Sodium Iodide → 2-(5-Chloro-3-methyl-1H-indazol-1-yl)-N-(1-hydroxy-2-methylpropan-2-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246465Notes

Reaction equation

HRID 246465 reaction equation
Br[C:2]1[N:3]=[C:4]2[C:10]([C:11]([NH:13][C:14]([CH3:18])([CH3:17])[CH2:15][OH:16])=[O:12])=[CH:9][N:8]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[C:5]2=[N:6][CH:7]=1.[I-].[Na+].CN[C@@H]1CCCC[C@H]1NC.[Cl:39][C:40]1[CH:41]=[C:42]2[C:46](=[CH:47][CH:48]=1)[NH:45][N:44]=[C:43]2[CH3:49].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.[Cu]I>[Cl:39][C:40]1[CH:41]=[C:42]2[C:46](=[CH:47][CH:48]=1)[N:45]([C:2]1[N:3]=[C:4]3[C:10]([C:11]([NH:13][C:14]([CH3:18])([CH3:17])[CH2:15][OH:16])=[O:12])=[CH:9][N:8]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[C:5]3=[N:6][CH:7]=1)[N:44]=[C:43]2[CH3:49]

Participants

8

Reactant 5

HCID 5238Sodium IodideHCID 62657Potassium Phosphate, TribasicHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 715756472-Bromo-N-(1-hydroxy-2-methylpropan-2-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideHCID 178434280HCID 178434280, compound

Product 1

HCID 712804642-(5-Chloro-3-methyl-1H-indazol-1-yl)-N-(1-hydroxy-2-methylpropan-2-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

2-Bromo-N-(1-hydroxy-2-methylpropan-2-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (110 mg, 248 μmol) was dissolved in toluene (1.4 mL), and copper (I) iodide (2.49 mg, 27.8 μmol), sodium iodide (74.4 mg, 496 μmol) and trans-N,N′-dimethylcyclohexane-1,2-diamine (9.00 mg, 63.3 μmol) added. The mixture was sealed under nitrogen and the mixture heated at 110° C. After 15 h, 5-chloro-3-methyl-1H-indazole (41.3 mg, 248 μmol) and potassium phosphate tribasic (111 mg 521 μmol) were added, the mixture degassed under vacuum, backfilled with nitrogen, and the mixture heated at in sealed tube at 110° C. for 24 h. The mixture was cooled, filtered, and the cake washed with ethyl acetate. The combined filtrates were concentrated and purified by chromatography (silica, 24 g Analogix column, 0-40% ethyl acetate in hexanes) to give 2-(5-Chloro-3-methyl-1H-indazol-1-yl)-N-(1-hydroxy-2-methylpropan-2-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Workup

  1. customThe mixture was sealed under nitrogen
  2. customthe mixture degassed under vacuum
  3. temperaturethe mixture heated at in sealed tube at 110° C. for 24 h
  4. temperatureThe mixture was cooled
  5. filtrationfiltered
  6. washthe cake washed with ethyl acetate
  7. concentrationThe combined filtrates were concentrated
  8. custompurified by chromatography (silica, 24 g Analogix column, 0-40% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-f286f3443b73491886ca59fc40105b15
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

Loading…