Hydrochloric Acid → HCID 178505416, compound

HRID 494734Notes

Reaction equation

HRID 494734 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:14]([C:15]([NH:17][NH2:18])=[O:16])=[CH:13][N:12]3[CH:19]=[CH:20][N:21]=[C:11]3[C:10]=2[Cl:22])=[C:4]([F:23])[CH:3]=1.[C:24](=S)=[S:25].[OH-].[K+].Cl>C(O)C.O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:14]([C:15]3[O:16][C:24]([SH:25])=[N:18][N:17]=3)=[CH:13][N:12]3[CH:19]=[CH:20][N:21]=[C:11]3[C:10]=2[Cl:22])=[C:4]([F:23])[CH:3]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6348Carbon DisulfideHCID 14797Potassium HydroxideHCID 58886642HCID 58886642, compound

Product 1

HCID 178505416HCID 178505416, compoundYield 31%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

7-(4-Bromo-2-fluoro-phenylamino)-8-chloro-imidazo[1,2-a]pyridine-6-carboxylic acid hydrazide (50 mg, 0.13 mmol) was suspended in ethanol (2.5 mL) and cooled to 0° C. Carbon disulfide (22 mg, 0.29 mmol) was added, followed by powdered potassium hydroxide (7 mg, 0.13 mmol). The reaction mixture was stirred under N2 for 1 hour at 0° C. and then for 30 minutes at room temperature. The reaction mixture was then brought to reflux and stirred under N2 for 5 days. The reaction mixture was diluted with water and acidified to pH 1-2 with aqueous 1 M HCl. This mixture was then extracted with ethyl acetate (2×). The combined organic layers were washed with saturated aqueous NaHCO3, saturated aqueous NaCl, dried over Na2SO4 and concentrated. Purification of the crude product was achieved by flash column chromatography (gradient of dichloromethane to 15:1 dichloromethane/methanol) and then trituration with diethyl ether and dichloromethane to yield the desired product (17 mg, 31%) as a yellow solid. MS ESI (+) m/z 440, 442 (M+, Cl, Br pattern) detected. 1H NMR (400 MHz, DMSO-d6) δ 9.29 (s, 1H), 8.16 (s, 1H), 8.08 (br s, 1H), 7.73 (s, 1H), 7.49 (d, 1H), 7.15 (d, 1H), 6.59 (t, 1H). 19F (376 MHz, DMSO-d6)−128.7 (s).

Workup

  1. waitfor 30 minutes at room temperature
  2. temperatureto reflux
  3. stirringstirred under N2 for 5 days
  4. extractionThis mixture was then extracted with ethyl acetate (2×)
  5. washThe combined organic layers were washed with saturated aqueous NaHCO3, saturated aqueous NaCl
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customPurification of the crude product

Sources & evidence

ORD record
ord-5c04c5b456224b70bc9b7b21de02e79d
Source dataset
uspto-grants-2009_05
Patent number
US07538120B2

Reaction notes

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