proline dl-form → 1-[2-indol-1-yl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-one

HRID 547488Notes

Reaction equation

HRID 547488 reaction equation
N1CCCC1C(O)=O.C(=O)([O-])[O-].[K+].[K+].Br[C:16]1[N:17]=[C:18]2[C:24]([C:25](=[O:30])[C:26]([CH3:29])([CH3:28])[CH3:27])=[CH:23][N:22]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[C:19]2=[N:20][CH:21]=1.[NH:39]1[C:47]2[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=2)[CH:41]=[CH:40]1.C(=O)(O)[O-].[Na+]>[Cu](I)I.CCOC(C)=O.CS(C)=O>[N:39]1([C:16]2[N:17]=[C:18]3[C:24]([C:25](=[O:30])[C:26]([CH3:29])([CH3:28])[CH3:27])=[CH:23][N:22]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[C:19]3=[N:20][CH:21]=2)[C:47]2[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=2)[CH:41]=[CH:40]1

Participants

9

Reactant 5

HCID 614proline dl-formHCID 798IndoleHCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 578292211-(2-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-yl)-2,2-dimethylpropane-1-one

Product 1

HCID 578296241-[2-indol-1-yl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-oneYield 61%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

DMSO (3 mL) was added to a mixture of copper iodide (10 mg; 0.05 mmol), d,1-proline (12 mg; 0.10 mmol), potassium carbonate (111 mg; 0.79 mmol), and 1-[2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-one (150 mg; 0.36 mmol). Indole (327 mg; 2.91 mmol) was added and the resulting mixture was stirred at 100° C. (oil bath) for 24 hrs. TLC analysis (25% EtOAc/hexanes) shows a new more-polar product. The reaction mixture was poured into 50 mL of saturated sodium bicarbonate solution and extracted with EtOAc (2×30 mL). The organic layers were combined, washed with brine, dried over MgSO4, and concentrated to give a yellow oil. Chromatography (SiO2; 0-15% EtOAc in hexanes) gives 1-[2-indol-1-yl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-one (61%; ms=449 [M+H]) as a light brown oil. Following general procedures described in these Examples, the SEM group was removed to give 1-(2-Indol-1-yl-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-dimethyl-propan-1-one (53%; MS=319 [M+H]; 1H NMR (DMSO): δ 8.83 (s), 8.64 (s), 8.48 (d, br), 8.11 (d, br), 7.69 (d), 7.31 (t), 7.21 (t), 6.83 (d) ppm; MP: 205-207° C.).

Workup

  1. extractionextracted with EtOAc (2×30 mL)
  2. washwashed with brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customto give a yellow oil

Sources & evidence

ORD record
ord-f792e67ea33946df97827accbee3d086
Source dataset
uspto-grants-2011_05
Patent number
US07939531B2

Reaction notes

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