Bromine → HCID 24966941, compound

HRID 655307Notes

Reaction equation

HRID 655307 reaction equation
[CH3:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH:11]([C:13]3[CH:14]=[C:15]4[C:20](=[CH:21][CH:22]=3)[N:19]=[CH:18][CH:17]=[CH:16]4)[CH3:12])=[N:9][N:10]=2)[N:7]=1.[Br:23]Br>C(O)(=O)C>[Br:23][C:17]1[CH:18]=[N:19][C:20]2[C:15]([CH:16]=1)=[CH:14][C:13]([CH:11]([C:8]1[N:6]3[N:7]=[C:2]([CH3:1])[CH:3]=[CH:4][C:5]3=[N:10][N:9]=1)[CH3:12])=[CH:22][CH:21]=2

Participants

4

Reactant 2

HCID 24408BromineHCID 24967301HCID 24967301, compound

Product 1

HCID 24966941HCID 24966941, compoundYield 37.1%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
100 °C

Procedure

2-Quinolin-6-yl-propionic acid hydrazide (intermediate 63) (500 mg, 2.32 mmol) was added to a stirred solution of 3-chloro-6-methylpyridazine (299 mg, 2.32 mmol) in n-butanol. The reaction mixture was heated at 120° C., overnight. The volatiles were removed in vacuo and the residue absorbed onto silica gel and purified by flash chromatography (SiO2, CH2Cl2:CH3OH 100:0-90:10) to obtain 6-[1-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)-ethyl]-quinoline (356 mg, 53% yield). To 6-[1-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)-ethyl]-quinoline (356 mg, 1.23 mmol) was added a dropwise solution of bromine (1.73 uL, 3.69 mmol) in acetic acid (3 mL). The reaction was heated at 100° C. for 2 hours. The reaction mixture was cooled to room temperature and the solvent removed in vacuo. A solution of 10% aq. NaSH (10 mL) was added and the product extracted with 10% methanol in dichloromethane. The organic phase was washed with 5% aqueous sodium sulfite. The filtrate was then concentrated in vacuo onto silica gel and purified by flash chromatography (SiO2, CH2Cl2:CH3OH 100:0-90:10) to return the title compound (168 mg, 37% yield). Analytical data presented in Table 1.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customthe solvent removed in vacuo
  3. additionA solution of 10% aq. NaSH (10 mL) was added
  4. extractionthe product extracted with 10% methanol in dichloromethane
  5. washThe organic phase was washed with 5% aqueous sodium sulfite
  6. concentrationThe filtrate was then concentrated in vacuo onto silica gel
  7. custompurified by flash chromatography (SiO2, CH2Cl2:CH3OH 100:0-90:10)

Sources & evidence

ORD record
ord-600a3ec1833e4ef3a6e4e498a5da418c
Source dataset
uspto-grants-2011_12
Patent number
US08071581B2

Reaction notes

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