Hydrochloric Acid → HCID 21111513, compound

HRID 494704Notes

Reaction equation

HRID 494704 reaction equation
C[O:2][C:3]([C:5]1[C:6]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([Br:22])=[CH:18][C:17]=2[Cl:23])=[C:7]([Cl:14])[C:8]2[N:9]([CH:11]=[CH:12][N:13]=2)[CH:10]=1)=O.Cl.[CH2:25]1COCC1>C(OCC)(=O)C.[CH3-].C[Al+]C.[CH-]1C=CC=C1.[CH-]1C=CC=C1.[Cl-].[Ti+3]>[Br:22][C:19]1[CH:20]=[CH:21][C:16]([NH:15][C:6]2[C:5]([C:3](=[O:2])[CH3:25])=[CH:10][N:9]3[CH:11]=[CH:12][N:13]=[C:8]3[C:7]=2[Cl:14])=[C:17]([Cl:23])[CH:18]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 58886653Methyl 7-(4-bromo-2-chlorophenylamino)-8-chloroimidazo[1,2-a]pyridine-6-carboxylate2×

Product 1

HCID 21111513HCID 21111513, compoundYield 28%

Reagents, catalysts & solvents 2

HCID 53384502mu-Chlorobis(eta5-cyclopentadienyl)(dimethylaluminum)-mu-methylenetitaniumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

This compound is prepared from compound 29, the product of Example 9, Step H. Tebbe reagent (μ-chloro-μ-methylene[bis(cyclopentadienyl)titanium]dimethyl-aluminum, 1 M solution in toluene, 0.12 mL, 0.12 mmol) was added to a solution of 7-(4-bromo-2-chloro-phenylamino)-8-chloro-imidazo[1,2-a]pyridine-6-carboxylic acid methyl ester (29) (25 mg, 0.061 mmol) in THF (1 mL) cooled to 0° C. The reaction mixture was warmed to room temperature and stirred for 1.5 hours. HCl (10% aqueous solution, 1 mL) was added and the mixture stirred for 16 hours. The reaction was diluted with ethyl acetate, washed with saturated aqueous sodium carbonate, dried over MgSO4, and concentrated. The crude material was purified by flash column chromoatography (dichloromethane to 100:1 dichloromethane/methanol) to provide the desired product (6.8 mg, 28%). MS APCI (−) m/z 396, 398, 400 (M-, Cl, Br pattern) detected. 1H NMR (400 MHz, CDCl3) δ 9.05 (br s, 1H), 8.81 (s, 1H), 7.71 (s, 2H), 7.55 (d, 1H), 7.22 (dd, 1H), 6.55 (d, 1H), 2.67 (s, 3H).

Workup

  1. temperatureThe reaction mixture was warmed to room temperature
  2. stirringthe mixture stirred for 16 hours
  3. washwashed with saturated aqueous sodium carbonate
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe crude material was purified by flash column chromoatography (dichloromethane to 100:1 dichloromethane/methanol)

Sources & evidence

ORD record
ord-c6011346ab4a4cf7bb4e830a63f3f0ae
Source dataset
uspto-grants-2009_05
Patent number
US07538120B2

Reaction notes

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