Borane;tetrahydrofuran → HCID 25031603, compound

HRID 1163099Notes

Reaction equation

HRID 1163099 reaction equation
[N:1]1([CH:6]2[CH2:10][CH2:9][N:8]([C:11]([C:13]3[CH:18]=[CH:17][C:16]([CH2:19][C:20]4[N:24]([CH2:25][CH3:26])[C:23]5[CH:27]=[CH:28][CH:29]=[CH:30][C:22]=5[N:21]=4)=[CH:15][CH:14]=3)=O)[CH2:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.B.O1CCCC1>O1CCCC1>[CH2:25]([N:24]1[C:23]2[CH:27]=[CH:28][CH:29]=[CH:30][C:22]=2[N:21]=[C:20]1[CH2:19][C:16]1[CH:15]=[CH:14][C:13]([CH2:11][N:8]2[CH2:9][CH2:10][C@H:6]([N:1]3[CH2:5][CH2:4][CH2:3][CH2:2]3)[CH2:7]2)=[CH:18][CH:17]=1)[CH3:26]

Participants

4

Reactant 2

HCID 2723981Borane;tetrahydrofuranHCID 25031338HCID 25031338, compound

Product 1

HCID 25031603HCID 25031603, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1,3′-bipyrrolidin-1′-yl(4-((1-ethyl-1H-benzo[d]imidazol-2-yl)methyl)phenyl)methanone (69 mg, 0.172 mmol, 1 eq) in anhydrous tetrahydrofuran (3 mL) was added borane-tetrahydrofuran complex (860 μL, 0.860 mmol, 1 M in tetrahydrofuran) and the reaction mixture has heated to reflux and allowed to stir for 3 h. The reaction mixture was cooled to room temperature, quenched by dropwise addition of methanol, and the solvent was evaporated under reduced pressure. The residue was treated with hydrogen chloride in methanol (5 mL) and heated at reflux for 1 h. The solvent was evaporated under reduced pressure and the residue was partitioned between dichloromethane and 1.0 N aqueous sodium hydroxide. The organic layer was separated and dried (sodium sulfate) and the solvent removed in vacuo. The residue was purified by flash column chromatography to afford the title product (65%). 1H NMR (300 MHz, DMSO-d6): 7.74-7.86 (m, 2 H), 7.43-7.56 (m, 6 H), 6.64 (s, 2 H), 4.62 (s, 2 H), 4.46 (q, 2 H), 4.22 (s, 2 H), 4.00-4.10 (m, 1 H), 3.44-3.55 (m, 1 H), 3.24-3.40 (m, 6 H), 3.09-3.18 (m, 1 H), 2.35-2.45 (m, 1 H), 2.12-2.24 (m, 1 H), 1.91-2.02 (m, 4 H), 1.27 (t, 3 H). 389.22 (M+H).

Workup

  1. temperaturethe reaction mixture has heated
  2. temperatureto reflux
  3. customquenched by dropwise addition of methanol
  4. customthe solvent was evaporated under reduced pressure
  5. additionThe residue was treated with hydrogen chloride in methanol (5 mL)
  6. temperatureheated
  7. temperatureat reflux for 1 h
  8. customThe solvent was evaporated under reduced pressure
  9. customthe residue was partitioned between dichloromethane and 1.0 N aqueous sodium hydroxide
  10. customThe organic layer was separated
  11. dry with materialdried (sodium sulfate)
  12. customthe solvent removed in vacuo
  13. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-610a8fb8defe42ceb18104880cc5769a
Source dataset
uspto-grants-2010_10
Patent number
US07820825B2

Reaction notes

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