Hexane → HCID 57932982, compound

HRID 1432594Notes

Reaction equation

HRID 1432594 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]([Br: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]>[Br:24][C:22]1[N:23]=[C:19]([C:6]2[N:2]([CH3:1])[N:3]=[CH:4][N:5]=2)[S:20][C:21]=1[C:25]1[N:29]2[N:30]=[C:31]([CH3:39])[CH:32]=[C:33]([CH:34]([CH2:35][CH3:36])[CH2:37][CH3:38])[C:28]2=[N:27][C:26]=1[CH3:40]

Participants

8

Reactant 4

HCID 8058HexaneHCID 224591H-1,2,4-Triazole, 1-methyl-HCID 68842708HCID 68842708, compoundHCID 178418339Butyllithium

Product 1

HCID 57932982HCID 57932982, compoundYield 57.9%

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. 152 mg of 3-(2,4-dibromo-thiazol-5-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (0.33 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. NH4Cl1 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:2M NH3 in MeOH=10:2:1) to give 88 mg of the title product. Yield 54%. mass spectrum (m/e): 461 (M+1). 1H-NMR (CDCl3): 7.98 (s, 1H), 6.77 (s, 1H), 4.44 (s, 3H), 3.35 (m, 1H), 2.59 (s, 3H), 2.55 (s, 3H), 1.88 (m, 4H), 0.92 (t, J=7.5 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. NH4Cl1
  7. extractionextracted with CH2Cl2
  8. dry with materialThe separated CH2Cl2 layer is dried over Na2SO4
  9. customevaporated

Sources & evidence

ORD record
ord-9bbf2f99ff464558a93089b8c87d0443
Source dataset
uspto-grants-2009_11
Patent number
US07612067B2

Reaction notes

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