1-Tributylstannyl-imidazo[1,5-a]pyridine → 2-imidazo[1,5-a]pyridin-1-yl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide

HRID 246347Notes

Reaction equation

HRID 246347 reaction equation
C([Sn](CCCC)(CCCC)[C:6]1[N:7]=[CH:8][N:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=12)CCC.[C:23]([NH:27][C:28]([C:30]1[C:38]2[C:33](=[N:34][CH:35]=[C:36](Br)[N:37]=2)[N:32]([CH2:40][O:41][CH2:42][CH2:43][Si:44]([CH3:47])([CH3:46])[CH3:45])[CH:31]=1)=[O:29])([CH3:26])([CH3:25])[CH3:24]>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>[C:23]([NH:27][C:28]([C:30]1[C:38]2[C:33](=[N:34][CH:35]=[C:36]([C:6]3[N:7]=[CH:8][N:9]4[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=34)[N:37]=2)[N:32]([CH2:40][O:41][CH2:42][CH2:43][Si:44]([CH3:47])([CH3:46])[CH3:45])[CH:31]=1)=[O:29])([CH3:26])([CH3:25])[CH3:24]

Participants

6

Reactant 2

HCID 712798061-Tributylstannyl-imidazo[1,5-a]pyridineHCID 715756452-bromo-N-(tert-butyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 712796032-imidazo[1,5-a]pyridin-1-yl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamideYield 45.5%

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

To a solution of 1-tributylstannyl-imidazo[1,5-a]pyridine (250 mg, 0.61 mmol) and 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide (150 mg, 0.35 mmol) in DMF (2 mL) were added Pd(PPh3)4 (20 mg, 0.018 mmol) and copper(I) iodide (13 mg, 0.07 mmol). The reaction mixture was heated at 90° C. for 2 h then cooled to room temperature overnight. The reaction was quenched with water and extracted with EtOAc (3×). The combined organics were washed with water (3×) then dried over MgSO4 and concentrated. The residue was chromatographed once with 0% to 3% MeOH/CH2Cl2 (0.5% NH4OH) and then with 30% to 60% EtOAc/hexanes to afford 74 mg (45%) of 2-imidazo[1,5-a]pyridin-1-yl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide as a bright yellow solid. 1H NMR (CDCl3, 300 MHz): δ (ppm) 9.35 (s, 1H), 8.53 (d, J=9.4 Hz, 1H), 8.38 (s, 1H), 8.32 (s, 1H), 8.12 (d, J=7.2 Hz, 1H), 8.05 (s, 1H), 6.99 (dd, J=9.4, 6.6 Hz, 1H), 6.77-6.87 (m, 1H), 5.74 (s, 2H), 3.54-3.68 (m, 2H), 1.67 (s, 9H), 0.90-1.06 (m, 2H), 0.00 (s, 9H).

Workup

  1. temperaturethen cooled to room temperature overnight
  2. customThe reaction was quenched with water
  3. extractionextracted with EtOAc (3×)
  4. washThe combined organics were washed with water (3×)
  5. dry with materialthen dried over MgSO4
  6. concentrationconcentrated
  7. customThe residue was chromatographed once with 0% to 3% MeOH/CH2Cl2 (0.5% NH4OH)

Sources & evidence

ORD record
ord-a54cc806dd384e6fb0868e3a570d8eb2
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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