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

HRID 2209146Notes

Reaction equation

HRID 2209146 reaction equation
[CH:1]1([N:4]2[C:8]3[C:9]([O:22][C@@H:23]([C@H:25]4[CH2:29][NH:28][C:27](=[O:30])[CH2:26]4)[CH3:24])=[CH:10][C:11](B4OC(C)(C)C(C)(C)O4)=[CH:12][C:7]=3[N:6]=[CH:5]2)[CH2:3][CH2:2]1.I[C:32]1[N:36](C(OC(C)(C)C)=O)[C:35]([CH3:44])=[N:34][CH:33]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].N#N>CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl.C(Cl)Cl.O.O1CCOCC1>[CH:1]1([N:4]2[C:8]3[C:9]([O:22][C@@H:23]([C@H:25]4[CH2:29][NH:28][C:27](=[O:30])[CH2:26]4)[CH3:24])=[CH:10][C:11]([C:32]4[NH:36][C:35]([CH3:44])=[N:34][CH:33]=4)=[CH:12][C:7]=3[N:6]=[CH:5]2)[CH2:3][CH2:2]1

Participants

9

Reactant 4

HCID 947NitrogenHCID 62657Potassium Phosphate, TribasicHCID 117843383HCID 117843383, compoundHCID 123319683(R)-4-((R)-1-((1-cyclopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one

Product 1

HCID 117844278(R)-4-((R)-1-((1-cyclopropyl-5-(2-methyl-1H-imidazol-5-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-oneYield 0.6%

Reagents, catalysts & solvents 4

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a microwave tube equipped with a stirring bar, (R)-4-((R)-1-((1-cyclopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzo[d]imidazol-7-yl)oxy)ethyl)pyrrolidin-2-one: (200 mg, 0.486 mmol), tert-butyl 5-iodo-2-methyl-1H-imidazole-1-carboxylate (299.7 mg, 0.973 mmol), 1,4-dioxane (1.1 mL), water (0.82 mL), K3PO4 (355 mg, 1.673 mmol) were added, the mixture was bubbled N2 for 5 minutes before bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (27.5 mg, 0.039 mmol) was added. The tube was sealed and heated in an oil bath at 100° C. overnight. DCM (200 mL) was added and the resulting mixture was washed with saturated NaHCO3 aqueous solution (20 mL×4), brine (20 mL×1), dried over anhydrous Na2SO4, filtered, removed solvents in vacuo. The resulting residue was passed a ISCO silica gel column (MeOH:DCM=5:95) to give light brown solids, 1.1 mg (yield 0.6%). 1H NMR (300 MHz, DMSO-d6) δ 11.71 (broad s, 1H), 8.00 (s, 1H), 7.59 (s, 1H), 7.49 (s, 1H), 7.44 (s, 1H), 7.24 (s, 1H), 4.81-4.70 (m, 1H), 3.66 (m, 1H), 3.47-3.33 (m, 1H), 3.19 (m, 1H), 2.81 (m, 1H), 2.31 (s, 3H), 2.42-2.20 (m, 2H), 1.31 (d, J=6.0 Hz, 3H), 1.13-1.04 (m, 2H), 1.04-0.93 (m, 2H) ppm; MS (ESI+) m/z 366.54 (M+H).

Workup

  1. customTo a microwave tube equipped with a stirring bar
  2. additionwas added
  3. customThe tube was sealed
  4. washthe resulting mixture was washed with saturated NaHCO3 aqueous solution (20 mL×4), brine (20 mL×1)
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. customremoved solvents in vacuo
  8. customto give light brown solids, 1.1 mg (yield 0.6%)

Sources & evidence

ORD record
ord-dc83d8afc39044bf9ef94c92c262f06b
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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