Nitrogen → 3-[3-chloro-5-(2-methyl-2H-[1,2,4]triazol-3-yl)-thiophen-2-yl]-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine

HRID 1432713Notes

Reaction equation

HRID 1432713 reaction equation
[CH2:1]([CH:3]([C:6]1[C:7]2[N:8]([CH:14]=C(C)C=2)[N:9]=C(OC)[CH:11]=1)[CH2:4][CH3:5])[CH3:2].Br[C:19]1[S:23][C:22]([C:24]2[N:28]([CH3:29])[N:27]=[CH:26][N:25]=2)=[CH:21][C:20]=1[Cl:30].[CH3:31][C:32]([O-])=O.[K+].[N:36]#N.CCO[C:41]([CH3:43])=O>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CN1C(=O)CCC1.CC([O-])=O.CC([O-])=O.[Pd+2].C(OP(OCC(Br)CBr)(OCC(Br)CBr)=O)C(Br)CBr>[Cl:30][C:20]1[CH:21]=[C:22]([C:24]2[N:28]([CH3:29])[N:27]=[CH:26][N:25]=2)[S:23][C:19]=1[C:14]1[N:8]2[N:9]=[C:41]([CH3:43])[CH:11]=[C:6]([CH:3]([CH2:4][CH3:5])[CH2:1][CH3:2])[C:7]2=[N:36][C:32]=1[CH3:31]

Participants

10

Reactant 5

HCID 947NitrogenHCID 8857Ethyl AcetateHCID 517044Potassium AcetateHCID 667214755-(5-Bromo-4-chloro-thiophen-2-yl)-1-methyl-[1,2,4]triazoleHCID 688419544-(1-Ethyl-propyl)-2-methoxy-6-methyl-pyrrolo[1,2-b]pyridazine

Product 1

HCID 579330443-[3-chloro-5-(2-methyl-2H-[1,2,4]triazol-3-yl)-thiophen-2-yl]-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazineYield 77%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
125 °C

Procedure

A solution of 4-(1-ethyl-propyl)-2-methoxy-6-methyl-pyrrolo[1,2-b]pyridazine (74.8 mg, 0.32 mmol), 5-(5-bromo-4-chloro-thiophen-2-yl)-1-methyl-1H-[1,2,4]triazole (107.5 mg, 0.38 mmol), TDBPP (10.4 mg, 0.016 mmol), tetrabutylammonium bromide (103.0 mg, 0.32 mmol), KOAc (158 mg, 1.61 mmol) in NMP (15 mL) is purged with N2 for 5 min. Pd(OAc)2 (3.6 mg, 0.016 mmol) is added and the resulting mixture is stirred at 125° C. for 6 h. The reaction is cooled to rt, and diluted with EtOAc (10 mL); filtered through silica gel; washed with EtOAc (3×30 mL). The filtrate is washed with H2O (3×30 m); dried with Na2SO4, filtered and concentrated. Purification of the crude material by silica gel chromatography gives the title compound (0.1062 g, 0.2469 mmol, 77%). 1H NMR (CDCl3): δ. 0.89 (t, J=7.6 Hz, 6H), 1.75-1.90 (m, 4H), 2.52 (s, 3H), 3.22-3.38 (m, 1H), 3.93 (s, 3H), 4.15 (s, 3H), 6.52 (s, 1H), 7.48 (s, 1H), 7.91 (s, 1H). ES-MS (m/z): calcd for C20H23ClN6OS (M+H)+: 431.9; found: 431.3.

Workup

  1. temperatureThe reaction is cooled to rt
  2. filtrationfiltered through silica gel
  3. washwashed with EtOAc (3×30 mL)
  4. washThe filtrate is washed with H2O (3×30 m)
  5. dry with materialdried with Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification of the crude material by silica gel chromatography

Sources & evidence

ORD record
ord-8799421ab10d4b569a232b52b2e6d15b
Source dataset
uspto-grants-2009_11
Patent number
US07612067B2

Reaction notes

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