Tetrahydrofuran → 1-(3-(2-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyridin-3-yl)azetidin-1-yl)ethanone

HRID 410289Notes

Reaction equation

HRID 410289 reaction equation
[NH:1]1[CH2:4][CH:3]([C:5]2[C:6]([O:11][C:12]3[CH:17]=[CH:16][C:15]([C:18]([C:20]4[NH:24][C:23]5[CH:25]=[CH:26][CH:27]=[CH:28][C:22]=5[N:21]=4)=[O:19])=[CH:14][CH:13]=3)=[N:7][CH:8]=[CH:9][CH:10]=2)[CH2:2]1.C(N(CC)CC)C.N1([C:41](=[O:43])[CH3:42])C=CN=C1.C1COCC1>CN(C=O)C>[NH:24]1[C:23]2[CH:25]=[CH:26][CH:27]=[CH:28][C:22]=2[N:21]=[C:20]1[C:18]([C:15]1[CH:16]=[CH:17][C:12]([O:11][C:6]2[C:5]([CH:3]3[CH2:4][N:1]([C:41](=[O:43])[CH3:42])[CH2:2]3)=[CH:10][CH:9]=[CH:8][N:7]=2)=[CH:13][CH:14]=1)=[O:19]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 171741-(1H-Imidazol-1-yl)ethanoneHCID 59327242HCID 59327242, compound

Product 1

HCID 593270351-(3-(2-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyridin-3-yl)azetidin-1-yl)ethanoneYield 11.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (4-(3-(azetidin-3-yl)pyridin-2-yloxy)phenyl)(1H-benzo[d]imidazol-2-yl)methanone (279 mg, 0.753 mmol) in DMF (1.0 mL) is added triethylamine (0.386 mL, 3.01 mmol) and 1-(1H-imidazol-1-yl)ethanone (100 mg, 0.904 mmol). A solid crashed out, so THF (2 mL) was added to give a homogeneous solution and the reaction was stirred at rt 2 h. The reaction mixture was quenched with saturated NaHCO3 and extracted with CH2Cl2 (3×5 mL). The combined organic layers were dried (MgSO4) and concentrated, then purified by RPHPLC to give 1-(3-(2-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyridin-3-yl)azetidin-1-yl)ethanone (35 mg, 0.085 mmol, 11.27% yield over 2 steps) as a white solid. MS (ESI, pos. ion) m/z: 413.0 (M+1). IC50 (uM) +++++.

Workup

  1. customto give a homogeneous solution
  2. customThe reaction mixture was quenched with saturated NaHCO3
  3. extractionextracted with CH2Cl2 (3×5 mL)
  4. dry with materialThe combined organic layers were dried (MgSO4)
  5. concentrationconcentrated
  6. custompurified by RPHPLC

Sources & evidence

ORD record
ord-591c59bdf27e4af7adea59b05d5efbf4
Source dataset
uspto-grants-2014_06
Patent number
US08759532B2

Reaction notes

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