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

HRID 246469Notes

Reaction equation

HRID 246469 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.[NH:39]1[C:47]2[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=2)[CH:41]=[N:40]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.[Cu]I>[OH:16][CH2:15][C:14]([NH:13][C:11]([C:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([N:39]3[C:47]4[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=4)[CH:41]=[N:40]3)[N:3]=2)[N:8]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[CH:9]=1)=[O:12])([CH3:18])[CH3:17]

Participants

8

Reactant 5

HCID 5238Sodium IodideHCID 92211H-IndazoleHCID 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-carboxamide

Product 1

HCID 71279713N-(1-Hydroxy-2-methylpropan-2-yl)-2-(1H-indazol-1-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideYield 74%

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-(1-hydroxy-2-methylpropan-2-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (140 mg, 316 μmol) in toluene (2 mL) was added copper (I) iodide (3.17 mg, 35.4 μmol), sodium iodide (94.7 mg, 631 mmol) and trans-N,N′-dimethylcyclohexane-1,2-diamine (11.5 mg, 80.5 μmol). The reaction mixture was sealed under nitrogen and the mixture heated at 110° C. for 15 h. To the mixture was added 1H-indazole (37.3 mg, 316 μmol) and potassium phosphate tribasic (141 mg, 663 μmol) then the reaction vessel 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-(1-Hydroxy-2-methylpropan-2-yl)-2-(1H-indazol-1-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (112 mg, 74%). 1H NMR (CDCl3) d: 9.21 (s, 1H), 8.58 (d, J=8.5 Hz, 1H), 8.35 (s, 1H), 8.30 (s, 1H), 8.01 (s, 1H), 7.87 (d, J=8.1 Hz, 1H), 7.53 (t, J=7.6 Hz, 1H), 7.31-7.41 (m, 1H), 5.73 (s, 2H), 3.81 (s, 2H), 3.55-3.66 (m, 2H), 1.55 (s, 6H), 0.89-1.04 (m, 2H), −0.02 (s, 9H).

Workup

  1. customThe reaction mixture was sealed under nitrogen
  2. customthe reaction vessel 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 Purification by chromatography (silica, 24 g Analogix column, 0-40% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-fa05924dcb914e1494901750e28cf085
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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