Borane;tetrahydrofuran → HCID 178461544, compound

HRID 730888Notes

Reaction equation

HRID 730888 reaction equation
[Cl:1][C:2]1[C:3]([N:10]2[CH2:15][CH2:14][N:13]([C:16]3[NH:17][C:18]4[C:24]([NH:25][C:26](=O)[C:27]5[CH:32]=[C:31]([F:33])[C:30]([F:34])=[C:29]([F:35])[CH:28]=5)=[CH:23][C:22]([C:37]([F:40])([F:39])[F:38])=[CH:21][C:19]=4[N:20]=3)[C@H:12]([CH3:41])[CH2:11]2)=[N:4][CH:5]=[C:6]([CH2:8][OH:9])[CH:7]=1.B.C1COCC1>C1COCC1.CO.[OH-].[Na+]>[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][OH:9])[CH:5]=[N:4][C:3]=1[N:10]1[CH2:15][CH2:14][N:13]([C:16]2[NH:17][C:18]3[C:24]([NH:25][CH2:26][C:27]4[CH:28]=[C:29]([F:35])[C:30]([F:34])=[C:31]([F:33])[CH:32]=4)=[CH:23][C:22]([C:37]([F:39])([F:38])[F:40])=[CH:21][C:19]=3[N:20]=2)[C@H:12]([CH3:41])[CH2:11]1

Participants

6

Reactant 2

HCID 2723981Borane;tetrahydrofuranHCID 178461548HCID 178461548, compound

Product 1

HCID 178461544HCID 178461544, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of N-{2-[(2R)-4-(3-chloro-5-hydroxymethyl-pyridin-2-yl)-2-methyl-piperazin-1-yl]-6-trifluoromethyl-3H-benzoimidazol-4-yl}-3,4,5-trifluoro-benzamide (120 mg, 0.2 mmol, Example 170c) in THF (1 mL) was added BH3.THF (0.6 mL, 0.6 mmol, Aldrich) dropwise with stirring at 0° C. The mixture was heated at reflux for 5 h, cooled to room temperature and diluted with 1:1 mixture of MeOH and 1N NaOH (2 mL). The mixture was stirred at room temperature for 30 min and extracted with EtOAc (2×20 mL). The combined organic extracts were washed with brine (10 mL), dried over Na2SO4 and filtered. The filtrate was evaporated in vacuo and the residue was purified by silica gel column chromatography, eluting with 5% MeOH/CH2Cl2 to give the title compound as a white solid. MS (ESI, pos. ion) m/e: 586 (M+1).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 5 h
  3. temperaturecooled to room temperature
  4. stirringThe mixture was stirred at room temperature for 30 min
  5. extractionextracted with EtOAc (2×20 mL)
  6. washThe combined organic extracts were washed with brine (10 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customThe filtrate was evaporated in vacuo
  10. customthe residue was purified by silica gel column chromatography
  11. washeluting with 5% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-b74106e3bef349b2901cf2ef56166f01
Source dataset
uspto-grants-2009_09
Patent number
US07582761B2

Reaction notes

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