2-(Tributylstannyl)pyrazine → (R)-4-((R)-1-((1-cyclopropyl-5-(pyrazin-2-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one

HRID 2209115Notes

Reaction equation

HRID 2209115 reaction equation
Br[C:2]1[CH:13]=[C:12]([O:14][C@@H:15]([C@H:17]2[CH2:21][NH:20][C:19](=[O:22])[CH2:18]2)[CH3:16])[C:5]2[N:6]([CH:9]3[CH2:11][CH2:10]3)[CH:7]=[N:8][C:4]=2[CH:3]=1.C([Sn](CCCC)(CCCC)[C:28]1[CH:33]=[N:32][CH:31]=[CH:30][N:29]=1)CCC>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCOCC1>[CH:9]1([N:6]2[C:5]3[C:12]([O:14][C@@H:15]([C@H:17]4[CH2:21][NH:20][C:19](=[O:22])[CH2:18]4)[CH3:16])=[CH:13][C:2]([C:28]4[CH:33]=[N:32][CH:31]=[CH:30][N:29]=4)=[CH:3][C:4]=3[N:8]=[CH:7]2)[CH2:11][CH2:10]1

Participants

5

Reactant 2

HCID 27373162-(Tributylstannyl)pyrazineHCID 117843361(R)-4-((R)-1-((5-bromo-1-cyclopropyl-1 h-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one

Product 1

HCID 117843928(R)-4-((R)-1-((1-cyclopropyl-5-(pyrazin-2-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-oneYield 23%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
130 °C

Procedure

Into a microwave-tube, a mixture of (R)-4-((R)-1-((5-bromo-1-cyclopropyl-1 h-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one: (100.0 mg, 0.27 mmol), 2-(tributylstannyl)pyrazine (152.0 mg, 0.91 mmol), Bis(triphenylphosphine)palladium(II) dichloride (28.9 mg, 0.04 mmol) and dioxane (8 mL). The reaction mixture was placed in the microwave reactor and heated at 130° C. for 30 min. Quenched with saturated KF, extracted with EtOAc (3×30 ml). The combined organic layers were washed with water (2×5 mL), concentrated, and purified by flash chromatography (100% EtOAc to 20% MeOH/EtOAc) to give 23.0 mg (23.0%) of (R)-4-((R)-1-((1-cyclopropyl-5-(pyrazin-2-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one:. 1H NMR (300 MHz, DMSO-d6) δ 9.34 (d, J=1.8 Hz, 1H), 8.69 (dd, J=1.8, 1.2 Hz, 1H), 8.56 (d, J=2.1 Hz 1H), 8.174 (s, 1H), 8.016 (d, J=0.9 Hz 1H), 7.62 (d, J=6 Hz 2H), 4.91-4.85 (m, 1H), 3.76-3.695 (m, 1H), 3.41 (t, J=9.2 Hz, 1H), 3.20 (dd, J=6.6, 6.9 Hz, 1H), 2.87-2.80 (m, 1H), 2.41-2.24 (m, 2H), 1.34 (d, J=6 Hz, 3H), 1.23-1.0 (m, 4H). LCMS-ESI+ (m/z): [M+H]+ calcd C20H21N5O2:363.17; found 364.09.

Workup

  1. customQuenched with saturated KF
  2. extractionextracted with EtOAc (3×30 ml)
  3. washThe combined organic layers were washed with water (2×5 mL)
  4. concentrationconcentrated
  5. custompurified by flash chromatography (100% EtOAc to 20% MeOH/EtOAc)

Sources & evidence

ORD record
ord-596059053e3c40ca891428882f325c32
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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