Hexane → HCID 68844348, compound

HRID 1432593Notes

Reaction equation

HRID 1432593 reaction equation
[CH3:1][N:2]1[CH:6]=[N:5][CH:4]=[N:3]1.C([Li])CCC.CCCCCC.Br[C:19]1[S:20][C:21]([C:25]2[N:29]3[N:30]=[C:31]([CH3:39])[CH:32]=[C:33]([CH:34]([CH2:37][CH3:38])[CH2:35][CH3:36])[C:28]3=[N:27][C:26]=2[CH3:40])=[C:22]([CH3:24])[N:23]=1>C1COCC1.[Cl-].[Zn+2].[Cl-].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:35]([CH:34]([C:33]1[C:28]2[N:29]([C:25]([C:21]3[S:20][C:19]([C:6]4[N:2]([CH3:1])[N:3]=[CH:4][N:5]=4)=[N:23][C:22]=3[CH3:24])=[C:26]([CH3:40])[N:27]=2)[N:30]=[C:31]([CH3:39])[CH:32]=1)[CH2:37][CH3:38])[CH3:36]

Participants

8

Reactant 4

HCID 8058HexaneHCID 224591H-1,2,4-Triazole, 1-methyl-HCID 68840065HCID 68840065, compoundHCID 178418339Butyllithium

Product 1

HCID 68844348HCID 68844348, compoundYield 22%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

82 mg of 1-Methyl-1,2,4-triazole (0.99 mmol) is dissolved in 2 ml of dry THF and cooled to −78° C. and 0.4 ml of n-butyllithium 2.5 M in hexane (0.99 mmol) is added. The reaction mixture is stirred at −78 C to room temperature for 10 min and cooled to −78° C. again. 1.98 ml of 0.5 M zinc chloride 0.5 M solution in THF (0.99 mmol) is added and stirred at −78 C to room temperature for 15 min. 265 mg of 3-(2-bromo-4-methyl-thiazol-5-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (0.66 mmol) and 27 mg of PdCl2(dppf) (0.033 mmol) are added and the vial is capped with a Teflon cap and heated at 80° C. for 2 days. The reaction is cooled to room temperature and quenched with sat. NH4Cl and extracted with CH2Cl2. The separated CH2Cl2 layer is dried over Na2SO4 and evaporated. The crude product is applied onto a silica-gel chromatography column (Hexane:AcOEt:2 M NH3 in MeOH=10:2:1) to give 57 mg of the title product. Yield 22%. mass spectrum (m/e): 396 (M+1). 1H-NMR (CDCl3): δ 7.96 (s, 1H), 6.77 (s, 1H), 4.45 (s, 3H), 3.36 (m, 1H), 2.55 (s, 3H), 2.52 (s, 3H), 2.47 (s, 3H), 1.88 (m, 4H), 0.92 (t, J=7.3 Hz, 6H).

Workup

  1. temperaturecooled to −78° C. again
  2. stirringstirred at −78 C to room temperature for 15 min
  3. customcap
  4. temperatureheated at 80° C. for 2 days
  5. temperatureThe reaction is cooled to room temperature
  6. customquenched with sat. NH4Cl
  7. extractionextracted with CH2Cl2
  8. dry with materialThe separated CH2Cl2 layer is dried over Na2SO4
  9. customevaporated

Sources & evidence

ORD record
ord-250ef17c81234bfdb4de48fe4e4e28b0
Source dataset
uspto-grants-2009_11
Patent number
US07612067B2

Reaction notes

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