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

HRID 1060816Notes

Reaction equation

HRID 1060816 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-2680f1e00cc04d2d9d334f901b28a9f6
Source dataset
uspto-grants-2003_02
Patent number
US06525070B2

Reaction notes

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