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

HRID 2209116Notes

Reaction equation

HRID 2209116 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]=[CH:32][CH:31]=[CH:30][N:29]=1)CCC>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]=[CH:32][CH:31]=[CH:30][N:29]=4)=[CH:3][C:4]=3[N:8]=[CH:7]2)[CH2:11][CH2:10]1

Participants

4

Reactant 2

HCID 6077842-(Tributylstannyl)pyridineHCID 117843361(R)-4-((R)-1-((5-bromo-1-cyclopropyl-1 h-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one

Product 1

HCID 117843033(R)-4-((R)-1-((1-cyclopropyl-5-(pyridin-2-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-oneYield 18.1%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
130 °C

Procedure

Into a microwave-tube, a mixture of (R)-4-((R)-1-((5-bromo-1-cyclopropyl-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one: (100.0 mg, 0.275 mmol), 2-(tributylstannyl)pyridine (152.0 mg, 0.412 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 18.0 mg (18.1%) of (R)-4-((R)-1-((1-cyclopropyl-5-(pyridin-2-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one. 1H NMR (300 MHz, DMSO-d6) δ 8.65 (d, J=7.5 Hz 1H), 8.127 (s, 1H), 8.04 (d, J=9.6 Hz 1H), 7.90-7.81 (m, 2H), 7.62 (d, J=0.9 Hz 1H), 7.60 (s, 1H), 7.324-7.283 (m, 1H), 4.856-4.815 (m, 1H), 3.742-3.695 (m, 1H), 3.41 (t, J=9.5 Hz, 1H), 3.21 (dd, J=6.3, 6.9 Hz, 1H), 2.862-2.811 (m, 1H), 2.426-2.24 (m, 2H), 1.33 (d, J=6.6 Hz, 3H), 1.266-1.016 (m, 4H). LCMS-ESI+ (m/z): [M+H]+ calcd C21H22N4O2:362.17; found 363.1.

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-820bbbc804364aad9815563ba43fc7b8
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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