Sodium Iodide → HCID 71280330, compound

HRID 246476Notes

Reaction equation

HRID 246476 reaction equation
Br[C:2]1[N:3]=[C:4]2[C:10]([C:11]([NH:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[CH:9][N:8]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[C:5]2=[N:6][CH:7]=1.[I-].[Na+].CN[C@@H]1CCCC[C@H]1NC.[F:38][CH:39]([F:50])[O:40][C:41]1[CH:42]=[C:43]2[C:47](=[CH:48][CH:49]=1)[NH:46][N:45]=[CH:44]2.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.[Cu]I>[C:14]([NH:13][C:11]([C:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([N:46]3[C:47]4[C:43](=[CH:42][C:41]([O:40][CH:39]([F:38])[F:50])=[CH:49][CH:48]=4)[CH:44]=[N:45]3)[N:3]=2)[N:8]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[CH:9]=1)=[O:12])([CH3:17])([CH3:16])[CH3:15]

Participants

8

Reactant 5

HCID 5238Sodium IodideHCID 62657Potassium Phosphate, TribasicHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 707005935-(Difluoromethoxy)-1H-indazoleHCID 715756452-bromo-N-(tert-butyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 71280330HCID 71280330, compoundYield 70%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
110 °C

Procedure

To a stirred solution of 2-bromo-N-tert-butyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (150 mg, 351 μmol) in toluene (1 mL) was added copper(I) iodide (3.52 mg, 39.3 μmol), sodium iodide (105 mg, 702 μmol) and trans-N,N′-dimethylcyclohexane-1,2-diamine (12.7 mg, 89.5 μmol). The reaction mixture was sealed under nitrogen and the mixture heated at 110° C. for 15 h. 5-(Difluoromethoxy)-1H-indazole (64.6 mg, 351 μmol) and potassium phosphate tribasic (156 mg, 737 μmol) were added then the mixture was degassed 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 N-tert-butyl-2-(5-(difluoromethoxy)-1H-indazol-1-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (130 mg, 70%). 1H NMR (CDCl3) δ: 9.18 (s, 1H), 8.61 (d, J=9.0 Hz, 1H), 8.36 (s, 1H), 8.27 (s, 1H), 7.69 (s, 1H), 7.59 (s, 1H), 7.32 (dd, J=9.0, 2.1 Hz, 1H), 6.27-6.89 (m, 1H), 5.72 (s, 2H), 3.53-3.66 (m, 2H), 1.61 (s, 9H), 0.87-1.07 (m, 2H), −0.03 (s, 9H).

Workup

  1. customThe reaction mixture was sealed under nitrogen
  2. customthe mixture was degassed
  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-cc4a0e342ada4481b5fbfd3f42cf4ed9
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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