Hydrochloric Acid → C-[6-(2,4-Dichloro-phenyl)-8-methoxy-3-morpholin-4-yl-imidazo[1,2-a]pyridin-7yl]-methylamine

HRID 420530Notes

Reaction equation

HRID 420530 reaction equation
Cl[C:2]1[C:3]2[N:4]([C:18]([N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)=[CH:19][N:20]=2)[CH:5]=[C:6]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][C:11]=2[Cl:17])[C:7]=1[C:8]#[N:9].C[O-].[Na+].B.C1C[O:34][CH2:33]C1.Cl>CO.O1CCOCC1.O>[Cl:17][C:11]1[CH:12]=[C:13]([Cl:16])[CH:14]=[CH:15][C:10]=1[C:6]1[C:7]([CH2:8][NH2:9])=[C:2]([O:34][CH3:33])[C:3]2[N:4]([C:18]([N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)=[CH:19][N:20]=2)[CH:5]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 2723981Borane;tetrahydrofuranHCID 10942334Sodium MethoxideHCID 66658969HCID 66658969, compound

Product 1

HCID 57906465C-[6-(2,4-Dichloro-phenyl)-8-methoxy-3-morpholin-4-yl-imidazo[1,2-a]pyridin-7yl]-methylamineYield 10%

Reagents, catalysts & solvents 3

HCID 312751,4-DioxaneCatalystHCID 887MethanolSolvent2×HCID 962WaterSolvent

Procedure

A mixture of 8-chloro-6-(2,4-dichloro-phenyl)-3-morpholin-4-yl-imidazo[1,2-a]pyridine-7-carbonitrile (20 mg, 0.05 mmol, prepared according to Example 30, Step 16.1) and NaOMe (8.2 mg, 0.15 mmol) in MeOH (0.5 mL) was refluxed and stirred for 1 h. The reaction mixture was cooled to RT, poured into water (20 ml) and extracted with DCM (3×10 mL). The combined organic fractions were dried over Na2SO4, filtered, and evaporated. The remaining residue was dissolved in THF and a BH3.THF complex (1.0 M solution in THF, 0.2 mL, 0.2 mmol) followed by a 4M HCl solution in dioxane (2 drops) were added. The reaction mixture was stirred and refluxed for 2 h30, then cooled to 0° C. (ice bath) and poured into MeOH. The resulting solution was evaporated to dryness and the remaining residue was purified by reverse phase prep-HPLC (Waters system) to give the title compound (2TFA salt, 3.3 mg, 0.005 mmol, 9% for 2 steps). MS: 407 [M+1]+; HPLC: AtRet=1.09.

Workup

  1. temperaturewas refluxed
  2. extractionextracted with DCM (3×10 mL)
  3. dry with materialThe combined organic fractions were dried over Na2SO4
  4. filtrationfiltered
  5. customevaporated
  6. dissolutionThe remaining residue was dissolved in THF
  7. additionwere added
  8. stirringThe reaction mixture was stirred
  9. temperaturerefluxed for 2 h30
  10. temperaturecooled to 0° C. (ice bath)
  11. customThe resulting solution was evaporated to dryness
  12. customthe remaining residue was purified by reverse phase prep-HPLC (Waters system)

Sources & evidence

ORD record
ord-cf097293f0584f62a1e7f1d2be41f0dd
Source dataset
uspto-grants-2012_01
Patent number
US08097617B2

Reaction notes

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