4-tributylstannanyl-1-(2,3,5-trifluoro-phenyl)-1H-imidazole → 2-[1-(2,3,5-trifluoro-phenyl)-1H-imidazol-4-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide

HRID 1898643Notes

Reaction equation

HRID 1898643 reaction equation
C([Sn](CCCC)(CCCC)[C:6]1[N:7]=[CH:8][N:9]([C:11]2[CH:16]=[C:15]([F:17])[CH:14]=[C:13]([F:18])[C:12]=2[F:19])[CH:10]=1)CCC.[C:28]([CH:30]1[CH2:33][N:32]([C:34](=[O:52])[C@H:35]([NH:39][C:40]([C:42]2[C:50]3[C:45](=[N:46][CH:47]=[C:48](Br)[N:49]=3)[NH:44][CH:43]=2)=[O:41])[CH:36]2[CH2:38][CH2:37]2)[CH2:31]1)#[N:29]>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:28]([CH:30]1[CH2:31][N:32]([C:34](=[O:52])[C@H:35]([NH:39][C:40]([C:42]2[C:50]3[C:45](=[N:46][CH:47]=[C:48]([C:6]4[N:7]=[CH:8][N:9]([C:11]5[CH:16]=[C:15]([F:17])[CH:14]=[C:13]([F:18])[C:12]=5[F:19])[CH:10]=4)[N:49]=3)[NH:44][CH:43]=2)=[O:41])[CH:36]2[CH2:38][CH2:37]2)[CH2:33]1)#[N:29]

Participants

6

Reactant 2

HCID 575166564-tributylstannanyl-1-(2,3,5-trifluoro-phenyl)-1H-imidazoleHCID 866578762-bromo-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide

Product 1

HCID 584385602-[1-(2,3,5-trifluoro-phenyl)-1H-imidazol-4-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amideYield 5%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
80 °C

Procedure

To the crude 4-tributylstannanyl-1-(2,3,5-trifluoro-phenyl)-1H-imidazole from Step 3 was added crude 2-bromo-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide (0.087 g, from Step 1) in 3 mL of DMF, Pd(PPh3)4 (0.032 g, 0.027 mmol) and CuI (0.021 g, 0.110 mmol). The dark yellow mixture was stirred at 80° C. for 16 h, then allowed to cool. The mixture was partitioned between 20 mL of ethyl acetate and 20 mL of a sat. aq. NH4Cl solution. The organic layer was washed with 20 mL of water+20 mL of a sat. aq. NaCl. The organic layer was dried over Na2SO4, filtered and concentrated. Column chromatography (0-10% MeOH/EtOAc) of the residue afforded 0.005 g (5%) of 2-[1-(2,3,5-trifluoro-phenyl)-1H-imidazol-4-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide as a yellow solid, ca. 85% pure. MS: (M+Na)+=543.

Workup

  1. temperatureto cool
  2. customThe mixture was partitioned between 20 mL of ethyl acetate and 20 mL of a sat. aq. NH4Cl solution
  3. washThe organic layer was washed with 20 mL of water+20 mL of a sat. aq. NaCl
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-df72601744934abe95904c42a62cb654
Source dataset
uspto-grants-2013_08
Patent number
US08518945B2

Reaction notes

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