HomeMCPWorkbenchSkills
HomeWorkbenchNotificationsMe
llms.txt · MCP GuidePrivacy Policy · Terms of Service · Supportv1.8.0
  1. Home
  2. /Reaction

5-Bromo-3-methylisothiazole → 6-(1-(6-(3-Methylisothiazol-5-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethyl)quinoline

HRID 40242
Notes
Print preview

Reaction equation

HRID 40242 reaction equation
Br[C:2]1[S:6][N:5]=[C:4]([CH3:7])[CH:3]=1.CC#N.C(=O)=O.Cl[C:15]1[CH:16]=[CH:17][C:18]2[N:19]([C:21]([CH:24]([C:26]3[CH:27]=[C:28]4[C:33](=[CH:34][CH:35]=3)[N:32]=[CH:31][CH:30]=[CH:29]4)[CH3:25])=[N:22][N:23]=2)[N:20]=1>C1COCC1.CN(C)C(=O)C.[Cl-].[Zn+2].[Cl-].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC(P(C(C)(C)C)[C-]1C=CC=C1)(C)C.C1C=CC([C-]2C(C3C=CC=CC=3)=C(C3C=CC=CC=3)C(C3C=CC=CC=3)=C2C2C=CC=CC=2)=CC=1.[Fe+2]>[CH3:7][C:4]1[CH:3]=[C:2]([C:15]2[CH:16]=[CH:17][C:18]3[N:19]([C:21]([CH:24]([C:26]4[CH:27]=[C:28]5[C:33](=[CH:34][CH:35]=4)[N:32]=[CH:31][CH:30]=[CH:29]5)[CH3:25])=[N:22][N:23]=3)[N:20]=2)[S:6][N:5]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

9

Reactant 3

HCID 6009595-Bromo-3-methylisothiazoleHCID 249687116-(1-(6-Chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethyl)quinolineHCID 86587134Acetonitrile dry ice

Product 1

HCID 441805966-(1-(6-(3-Methylisothiazol-5-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethyl)quinoline

Reagents, catalysts & solvents 5

HCID 3007855Zincchloride
Catalyst
HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst
HCID 129828017Ditert-butyl(cyclopenta-2,4-dien-1-yl)phosphane;iron(2+);(2,3,4,5-tetraphenylcyclopenta-1,4-dien-1-yl)benzeneCatalyst
HCID 8028TetrahydrofuranSolvent
HCID 31374DimethylacetamideSolvent

Conditions

Temperature
-45 °C

Procedure

To a solution of 5-bromo-3-methylisothiazole (1.00 g, 5.6 mmol) in 10 mL of THF at −45° C. (CH3CN/dry ice) was added isopropylmagnesium chloride LiCl complex (7.9 ml, 7.9 mmol) (LiCl complex, 1M in THF). The mixture was stirred at −45° C. for 20 minutes and was added zinc chloride, 0.5m in thf (17 ml, 8.4 mmol) slowly via a syringe. The mixture was then warmed up to rt and continued to stir for additional 30 minutes. 6-(1-(6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethyl)quinoline (0.5787 g, 1.9 mmol), tris(dibenzylideneacetone)dipalladium (o) (0.51 g, 0.56 mmol) and Q-Phos (0.65 g) in 15 mL of N,N-dimethyl acetamide was added to the reaction mixture. The reaction was warmed up to 50° C. for 6 h and was quenched with 50 mL of satd. NH4Cl aq. solution. The mixture was extracted with 150 mL of EtOAc and the organic phase was washed with 60 mL of brine. The aqueous phases were extracted with 100 mL EtOAc again. The combined organic phases were dried over Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (EtOAc to 15% MeOH in EtOAc) to give red solid as desired product 6-(1-(6-(3-methylisothiazol-5-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethyl)quinoline. MS (ESI, pos. ion) m/z: 373.2 (M+1).

Workup

  1. temperatureThe mixture was then warmed up to rt
  2. stirringto stir for additional 30 minutes
  3. temperatureThe reaction was warmed up to 50° C. for 6 h
  4. customwas quenched with 50 mL of satd
  5. extractionThe mixture was extracted with 150 mL of EtOAc
  6. washthe organic phase was washed with 60 mL of brine
  7. extractionThe aqueous phases were extracted with 100 mL EtOAc again
  8. dry with materialThe combined organic phases were dried over Na2SO4
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by a silica gel column chromatography (EtOAc to 15% MeOH in EtOAc)

Sources & evidence

ORD record
ord-d0d8005de9ab4b179aabb396a7613700
Source dataset
uspto-grants-2013_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08524900B2

Reaction notes

Loading…

On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes