Sodium Bicarbonate → [4-(3,4-Dichloro-phenoxy)-[1,4']bipiperidinyl-1'-yl]-(6-fluoro-imidazo[1,2-a]pyridin-2-yl)-methanone

HRID 1293535Notes

Reaction equation

HRID 1293535 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:18]=[CH:19][C:20]=1[Cl:21])[O:5][CH:6]1[CH2:11][CH2:10][N:9]([CH:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)[CH2:8][CH2:7]1.F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1.[F:46][C:47]1[CH:48]=[CH:49][C:50]2[N:51]([CH:53]=[C:54]([C:56](O)=[O:57])[N:55]=2)[CH:52]=1.C([O-])(O)=O.[Na+]>ClCCl.C(N(CC)CC)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:18]=[CH:19][C:20]=1[Cl:21])[O:5][CH:6]1[CH2:7][CH2:8][N:9]([CH:12]2[CH2:13][CH2:14][N:15]([C:56]([C:54]3[N:55]=[C:50]4[CH:49]=[CH:48][C:47]([F:46])=[CH:52][N:51]4[CH:53]=3)=[O:57])[CH2:16][CH2:17]2)[CH2:10][CH2:11]1

Participants

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 2733179PyBroPHCID 223974344-(3,4-Dichloro-phenoxy)-[1,4']bipiperidineHCID 223975086-Fluoroimidazo[1,2-a]pyridine-2-carboxylic acid

Product 1

HCID 22397486[4-(3,4-Dichloro-phenoxy)-[1,4']bipiperidinyl-1'-yl]-(6-fluoro-imidazo[1,2-a]pyridin-2-yl)-methanoneYield 34.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Procedure

4-(3,4-Dichloro-phenoxy)-[1,4′]bipiperidine (0.2 g, see step b of Example 2) was dissolved in dichloromethane (5 ml), bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (PYBROP™; 0.425 g), 6-fluoro-imidazo[1,2-a]pyridine-2-carboxylic acid (0.126 g) and triethylamine (0.254 ml) were added. After 16 hours at room temperature dichloromethane and aqueous NaHCO3 solution were added. The product was extracted with dichloromethane, the combined organic extracts were washed with water, dried with MgSO4 and concentrated. Purification by reverse phase HPLC (with a gradient eluent system (45% MeCN/NH4OAc aq (0.1%) to 95% MeCN//NH4OAc aq (0.1%)) (any excess NH4OAc was removed by dissolving the compound in ethyl acetate and washing with aqueous saturated NaHCO3 followed by drying of the organics with magnesium sulfate and evaporation of solvent) gave the title compound (0.104 g).

Workup

  1. extractionThe product was extracted with dichloromethane
  2. washthe combined organic extracts were washed with water
  3. dry with materialdried with MgSO4
  4. concentrationconcentrated
  5. customPurification by reverse phase HPLC (with a gradient eluent system (45% MeCN/NH4OAc aq (0.1%) to 95% MeCN//NH4OAc aq (0.1%)) (any excess NH4OAc
  6. customwas removed
  7. dissolutionby dissolving the compound in ethyl acetate
  8. washwashing with aqueous saturated NaHCO3
  9. customby drying of the
  10. customorganics with magnesium sulfate and evaporation of solvent)

Sources & evidence

ORD record
ord-fc3300b198c14616aeb97f0e2003f7db
Source dataset
uspto-grants-2007_07
Patent number
US07238811B2

Reaction notes

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