Dimethylformamide → N-tert-butyl-2-(6-fluoroimidazo[1,5-a]pyridin-1-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246550Notes

Reaction equation

HRID 246550 reaction equation
Br[C:2]1[N:3]=[C:4]2[C:10]([C:11]([NH:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[CH:9][N:8]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[C:5]2=[N:6][CH:7]=1.[F:26][C:27]1[CH:28]=[CH:29][C:30]2[N:31]([CH:33]=[N:34][C:35]=2[Sn](CCCC)(CCCC)CCCC)[CH:32]=1.CN(C=O)C>CCOCC.C(OCC)(=O)C.O.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:14]([NH:13][C:11]([C:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([C:35]3[N:34]=[CH:33][N:31]4[CH:32]=[C:27]([F:26])[CH:28]=[CH:29][C:30]=34)[N:3]=2)[N:8]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[CH:9]=1)=[O:12])([CH3:17])([CH3:16])[CH3:15]

Participants

9

Reactant 3

HCID 6228DimethylformamideHCID 712799216-Fluoro-1-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 71280199N-tert-butyl-2-(6-fluoroimidazo[1,5-a]pyridin-1-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideYield 32.3%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

To a mixture of 2-bromo-N-tert-butyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (250 mg, 585 μmol), 6-fluoro-1-(tributylstannyl)imidazo[1,5-a]pyridine (400 mg, 564 μmol), tetrakis(triphenylphosphine)palladium (0) (33.8 mg, 29.2 μmol) and copper (I) iodide (22.3 mg, 117 μmol) was added DMF (5.85 mL) and the reaction mixture heated to 90° C. under N2. After 16 h the reaction was diluted with ether, ethyl acetate and water. The organic phase was separated and washed with water (1×) and brine (2×) then dried (MgSO4), filtered and concentrated in vacuo. Purification by chromatography (silica, 30-80% ethyl acetate/hexanes) gave N-tert-butyl-2-(6-fluoroimidazo[1,5-a]pyridin-1-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (88 mg, 182 μmol, 31.2%) as a yellow solid. MS (M+H)+=483.3; 1H NMR (CDCl3-d) δ: 9.34 (s, 1H), 8.54 (m, 1H), 8.34 (s, 2H), 8.04 (m, 1H), 7.98 (s, 1H), 6.9 (m, 1H), 5.74 (s, 2H), 3.61 (d, J=8.3 Hz, 2H), 1.66 (s, 9H); 0.98 (t, J=8.3 Hz, 2H), 0.0 (s, 9H).

Workup

  1. customThe organic phase was separated
  2. washwashed with water (1×) and brine (2×)
  3. dry with materialthen dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by chromatography (silica, 30-80% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-671117fb22c844d2b24c226f149ef6c9
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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