2-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde → 2-(1-methyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde

HRID 246407Notes

Reaction equation

HRID 246407 reaction equation
Br[C:2]1[N:3]=[C:4]2[C:10]([CH:11]=[O:12])=[CH:9][N:8]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[C:5]2=[N:6][CH:7]=1.[CH3:21][N:22]1[C:30]2[CH2:29][CH2:28][CH2:27][CH2:26][C:25]=2[C:24]([Sn](CCCC)(CCCC)CCCC)=[N:23]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>[CH3:21][N:22]1[C:30]2[CH2:29][CH2:28][CH2:27][CH2:26][C:25]=2[C:24]([C:2]2[N:3]=[C:4]3[C:10]([CH:11]=[O:12])=[CH:9][N:8]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[C:5]3=[N:6][CH:7]=2)=[N:23]1

Participants

6

Reactant 2

HCID 578296122-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehydeHCID 712804701-methyl-3-(tributylstannyl)-4,5,6,7-tetrahydro-1H-indazole

Product 1

HCID 866779782-(1-methyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehydeYield 56.5%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
90 °C

Procedure

2-Bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (406 mg, 1.14 mmol) and 1-methyl-3-(tributylstannyl)-4,5,6,7-tetrahydro-1H-indazole (485 mg, 1.14 mmol) were dissolved in DMF (3.00 mL) under argon, tetrakis(triphenylphosphine)palladium (0) (65.9 mg, 57.0 μmol) and CuI (43.4 mg, 228 μmol, Eq: 0.20) were added and the mixture sonicated for 5 min with bubbling argon. The reaction mixture was stirred at 90° C. (oil bath temperature) for 18 h. The reaction mixture was concentrated under high vacuum and the dark yellow solid residue was purified by chromatography (80 g column, 50 μm from SiliCycle) gradient 0-50% EtOAc in hexanes over 30 min) to give 2-(1-methyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (265 mg, 644 μmol, 56.5%) as a light yellow solid. MS (M+H)+=412; 1H NMR (CDCl3) δ: 10.50 (s, 1H), 9.07 (s, 1H), 8.29 (s, 1H), 5.77 (s, 2H), 3.89 (s, 3H), 3.57-3.72 (m, 2H), 3.05 (t, J=6.0 Hz, 2H), 2.69 (t, J=6.0 Hz, 2H), 1.80-2.02 (m, 4H), 0.92-1.09 (m, 2H), 0.00 (s, 9H).

Workup

  1. customthe mixture sonicated for 5 min with bubbling argon
  2. concentrationThe reaction mixture was concentrated under high vacuum
  3. customthe dark yellow solid residue was purified by chromatography (80 g column, 50 μm from SiliCycle) gradient 0-50% EtOAc in hexanes over 30 min)

Sources & evidence

ORD record
ord-a9bf5f2f06704c18b46bd1c242d95834
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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