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

HRID 246472

Reaction equation

HRID 246472 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.[CH3:38][O: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>[C:14]([NH:13][C:11]([C:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([N:45]3[C:46]4[C:42](=[CH:41][C:40]([O:39][CH3:38])=[CH:48][CH:47]=4)[CH:43]=[N:44]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 133468605-Methoxy-1H-indazoleHCID 715756452-bromo-N-(tert-butyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 71279900N-tert-Butyl-2-(5-methoxy-1H-indazol-1-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideYield 13%

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-Methoxy-1H-indazole (52.0 mg, 351 μmol) and potassium phosphate tribasic (156 mg, 737 μmol) were added and the mixture was degassed, filled 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 N-tert-Butyl-2-(5-methoxy-1H-indazol-1-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (22 mg, 13%). 1H NMR (CDCl3) δ: 9.18 (s, 1H), 8.52 (d, J=9.0 Hz, 1H), 8.34 (s, 1H), 8.20 (s, 1H), 7.75 (s, 1H), 7.10-7.22 (m, 2H), 5.71 (s, 2H), 3.93 (s, 3H), 3.53-3.64 (m, 2H), 1.61 (s, 9H), 0.89-1.00 (m, 2H), −0.03 (s, 9H).

Workup

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

Sources & evidence

ORD record
ord-c132220a69a7461bb40a541e2594e612
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Linked notes

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