Nitrogen → HCID 57932923, compound

HRID 1432701Notes

Reaction equation

HRID 1432701 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]2[C:9]([CH:10]([CH2:14][CH2:15][CH3:16])[CH2:11][CH2:12][CH3:13])=[CH:8][C:7]([CH3:17])=[N:6][N:5]2[CH:18]=1.Br[C:20]1[S:24][C:23]([C:25]2[N:29]([CH3:30])[N:28]=[CH:27][N:26]=2)=[CH:22][C:21]=1[Cl:31].CC([O-])=O.[K+].N#N>CCCC[N+](CCCC)(CCCC)CCCC.[Br-].CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2].C(OP(OCC(Br)CBr)(OCC(Br)CBr)=O)C(Br)CBr.CN1C(=O)CCC1>[Cl:31][C:21]1[CH:22]=[C:23]([C:25]2[N:29]([CH3:30])[N:28]=[CH:27][N:26]=2)[S:24][C:20]=1[C:18]1[N:5]2[N:6]=[C:7]([CH3:17])[CH:8]=[C:9]([CH:10]([CH2:14][CH2:15][CH3:16])[CH2:11][CH2:12][CH3:13])[C:4]2=[N:3][C:2]=1[CH3:1]

Participants

10

Reactant 4

HCID 947NitrogenHCID 517044Potassium AcetateHCID 667214755-(5-Bromo-4-chloro-thiophen-2-yl)-1-methyl-[1,2,4]triazoleHCID 68840997HCID 68840997, compound

Product 1

HCID 57932923HCID 57932923, compoundYield 56%

Reagents, catalysts & solvents 5

HCID 31356Tris(2,3-dibromopropyl) PhosphateCatalystHCID 74236Tetrabutylammonium BromideCatalystHCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
125 °C

Procedure

A slurry of 2,6-dimethyl-8-(1-propyl-butyl)-imidazo[1,2-b]pyridazine (below) (0.30 g, 1.22 mmol), 5-(5-bromo-4-chloro-thiophen-2-yl)-1-methyl-[1,2,4]triazole (below) (0.41 g, 1.47 mmol), KOAc (0.60 g, 6.11 mmol), TBABr (0.39 g, 1.22 mmol), and NMP (3 mL) is de-gassed with N2 for 30 minutes. Pd(OAc)2 (0.014 g, 0.061 mmol) and TDBPP (0.040 g, 0.061 mmol) are added and the solution heated at 125° C. for 2.5 hours. The solution is diluted with EtOAc (50 mL), washed with water (3×50 mL), brine (50 mL), dried over MgSO4, filtered and concentrated. The residue is purified by ISCO flash chromatography (20%-40% EtOAc gradient) furnish the title compound (0.30 g, 0.68 mmol, 56%). 1H NMR (CDCl3) δ 0.89 (t, J=7.4 Hz, 6H), 1.14-1.39 (m, 4H), 1.76 (q, J=16.3, 7.7 Hz, 4H), 2.51 (s, 3H), 2.52 (s, 3H), 3.41-3.50 (m, 1H), 4.15 (s, 3H), 6.73 (s, 1H), 7.48 (s, 1H), 7.90 (s, 1H). LC/MS (m/z): calcd. for C22H27ClN6S (M+H)+: 443.2; found: 443.3.

Workup

  1. washwashed with water (3×50 mL), brine (50 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue is purified by ISCO flash chromatography (20%-40% EtOAc gradient)

Sources & evidence

ORD record
ord-0cb51add002340f693c4775792ddb947
Source dataset
uspto-grants-2009_11
Patent number
US07612067B2

Reaction notes

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