2-bromo-N-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide → N-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-(6-fluoro-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide

HRID 246782Notes

Reaction equation

HRID 246782 reaction equation
Br[C:2]1[N:7]=[C:6]2[C:8]([C:30]([NH:32][C:33]([CH3:44])([CH3:43])[CH2:34][O:35][Si:36]([C:39]([CH3:42])([CH3:41])[CH3:40])([CH3:38])[CH3:37])=[O:31])=[CH:9][N:10]([C:11]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:5]2=[N:4][CH:3]=1.[F:45][C:46]1[CH:54]=[C:53]2[C:49]([C:50]([Sn](CCCC)(CCCC)CCCC)=[N:51][NH:52]2)=[CH:48][CH:47]=1>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[Si:36]([O:35][CH2:34][C:33]([NH:32][C:30]([C:8]1[C:6]2=[N:7][C:2]([C:50]3[C:49]4[C:53](=[CH:54][C:46]([F:45])=[CH:47][CH:48]=4)[NH:52][N:51]=3)=[CH:3][N:4]=[C:5]2[N:10]([C:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:9]=1)=[O:31])([CH3:43])[CH3:44])([C:39]([CH3:41])([CH3:40])[CH3:42])([CH3:38])[CH3:37]

Participants

6

Reactant 2

HCID 866780042-bromo-N-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamideHCID 1784482326-fluoro-3-(tributylstannyl)-1H-indazole

Product 1

HCID 71279668N-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-(6-fluoro-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamideYield 20.5%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

2-Bromo-N-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (287 mg, 0.674 mmol) and 6-fluoro-3-(tributylstannyl)-1H-indazole (450 mg, 0.674 mmol) were dissolved in DMF (8 mL) under nitrogen. Pd(PPh3)4 (39 mg, 0.034 mmol) and CuI (26 mg, 0.136 mmol) were added and the mixture was sonicated for 5 min while bubbling nitrogen through it. The reaction mixture was then stirred at 85° C. for 4 h. The mixture was cooled, concentrated in vacuo and then purified by chromatography (silica, petroleum ether:EtOAC 5:1 v/v) to give N-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-(6-fluoro-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (100 mg, 20%) as a white solid. 1H NMR (300 MHz, CD3C1): δ 8.55 (s, 1H), 8.35 (s, 1H), 8.13 (s, 1H), 8.32 (s, 1H), 7.49-7.47 (m, 3H), 7.29-7.01 (m, 15H), 3.87 (s, 2H), 1.55 (s, 6H), 0.78 (s, 9H), 0.02 (s, 6H). LC-MS: 725.3 [M+H]+.

Workup

  1. customthe mixture was sonicated for 5 min
  2. customwhile bubbling nitrogen through it
  3. temperatureThe mixture was cooled
  4. concentrationconcentrated in vacuo
  5. custompurified by chromatography (silica, petroleum ether:EtOAC 5:1 v/v)

Sources & evidence

ORD record
ord-3f881b9c9a474acb8e01160381479a3a
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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