Sodium Iodide → HCID 71280168, compound

HRID 246467Notes

Reaction equation

HRID 246467 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.[F:39][C:40]1[CH:41]=[C:42]2[C:46](=[CH:47][CH:48]=1)[NH:45][N:44]=[CH:43]2.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.[Cu]I>[F: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]=[CH:43]2

Participants

8

Reactant 5

HCID 5238Sodium IodideHCID 62657Potassium Phosphate, TribasicHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 178424865-Fluoro-1H-indazoleHCID 715756472-Bromo-N-(1-hydroxy-2-methylpropan-2-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 71280168HCID 71280168, compoundYield 90%

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. for 15 h. 5-fluoro-1H-indazole (33.8 mg, 248 μmol) and potassium phosphate tribasic (111 mg 521 μmol) were added, the mixture degassed with nitrogen, and the mixture heated at in sealed tube at 110° C. for 15 h. The mixture was filtered, the cake washed with ethyl acetate, and the filtrate concentrated in vacuo. Purification by chromatography (silica, 24 g Analogix column, 0-40% ethyl acetate in hexanes) gave 2-(5-Fluoro-1H-indazol-1-yl)-N-(1-hydroxy-2-methylpropan-2-yl)-5((2(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (111 mg, 90%). 1H NMR (CDCl3) δ: 9.19 (s, 1H), 8.55 (dd, J=9.1, 4.2 Hz, 1H), 8.37 (s, 1H), 8.26 (s, 1H), 7.92 (s, 1H), 7.49 (dd, J=8.1, 2.3 Hz, 1H), 7.28-7.33 (m, 1H), 5.73 (s, 2H), 3.81 (s, 2H), 3.53-3.66 (m, 2H), 1.54 (s, 6H), 0.91-1.01 (m, 2H), −0.02 (s, 9H).

Workup

  1. customThe mixture was sealed under nitrogen
  2. customthe mixture degassed with nitrogen
  3. temperaturethe mixture heated at in sealed tube at 110° C. for 15 h
  4. filtrationThe mixture was filtered
  5. washthe cake washed with ethyl acetate
  6. concentrationthe filtrate concentrated in vacuo
  7. customPurification by chromatography (silica, 24 g Analogix column, 0-40% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-05e176ac4bba4dcdafae49c9a856d9ea
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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