Hydrochloric Acid → 8-Amino-6-(2,4-dichloro-phenyl)-3-morpholin-4-yl-imidazo[1,2-a]pyridine-7-carbonitrile

HRID 420528Notes

Reaction equation

HRID 420528 reaction equation
[N:1]([C:4]1[C:5]2[N:6]([C:20]([N:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)=[CH:21][N:22]=2)[CH:7]=[C:8]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:13]=2[Cl:19])[C:9]=1[C:10]#[N:11])=[N+]=[N-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Cl>CO.O>[NH2:1][C:4]1[C:5]2[N:6]([C:20]([N:23]3[CH2:24][CH2:25][O:26][CH2:27][CH2:28]3)=[CH:21][N:22]=2)[CH:7]=[C:8]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:13]=2[Cl:19])[C:9]=1[C:10]#[N:11]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 86634891HCID 86634891, compound

Product 1

HCID 666592488-Amino-6-(2,4-dichloro-phenyl)-3-morpholin-4-yl-imidazo[1,2-a]pyridine-7-carbonitrileYield 87.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

A mixture of crude 8-azido-6-(2,4-dichloro-phenyl)-3-morpholin-4-yl-imidazo[1,2-a]pyridine-7-carbonitrile (144 mg, 0.33 mmol) and triphenylphosphine (133 mg, 0.51 mmol) in MeOH (4 mL) was stirred and refluxed for 1 h. 2M HCl in water (1 mL) was added and the reaction mixture was further refluxed for 1 h. The reaction mixture was cooled to RT, concentrated under vacuum and the remaining residue was dissolved in water. The aqueous solution was basified to pH 12 by the addition of a 2M NaOH solution in water. The resulting slurry was extracted with DCM (3×) and the combined organic fractions were dried over Na2SO4, filtered and evaporated. The remaining residue was purified by Combi-Flash Companion™ (Isco Inc.) column chromatography (SiO2; gradient elution, DCM/MeOH 99:1→92:8) to yield the title compound (112 mg, 0.29 mmol, 87%). MS: 388 [M+1]+; HPLC: AtRet=1.91; TLC: RF 0.56 (DCM/MeOH 95:5).

Workup

  1. temperaturerefluxed for 1 h
  2. temperaturethe reaction mixture was further refluxed for 1 h
  3. concentrationconcentrated under vacuum
  4. dissolutionthe remaining residue was dissolved in water
  5. additionThe aqueous solution was basified to pH 12 by the addition of a 2M NaOH solution in water
  6. extractionThe resulting slurry was extracted with DCM (3×)
  7. dry with materialthe combined organic fractions were dried over Na2SO4
  8. filtrationfiltered
  9. customevaporated
  10. customThe remaining residue was purified by Combi-Flash Companion™ (Isco Inc.) column chromatography (SiO2; gradient elution, DCM/MeOH 99:1→92:8)

Sources & evidence

ORD record
ord-808d183f8c0643ef8c8815fdee5d9336
Source dataset
uspto-grants-2012_01
Patent number
US08097617B2

Reaction notes

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