Tris(2,3-dibromopropyl) Phosphate → 3-[3-Chloro-5-(2-methyl-2H-[1,2,4]triazol-3-yl)-thiophen-2-yl]-8-(1-ethyl-propyl)-6-methyl-2-trifluoromethyl-imidazo[1,2-b]pyridazine

HRID 1432731Notes

Reaction equation

[CH2:1]([CH:3]([C:6]1[C:7]2[N:8]([CH:13]=[C:14]([C:16]([F:19])([F:18])[F:17])[N:15]=2)[N:9]=[C:10]([CH3:12])[CH:11]=1)[CH2:4][CH3:5])[CH3:2].Br[C:21]1[S:25][C:24]([C:26]2[N:30]([CH3:31])[N:29]=[CH:28][N:27]=2)=[CH:23][C:22]=1[Cl:32].CC([O-])=O.[K+].C(OP(OCC(Br)CBr)(OCC(Br)CBr)=O)C(Br)CBr>CCCC[N+](CCCC)(CCCC)CCCC.[Br-].CN1C(=O)CCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:32][C:22]1[CH:23]=[C:24]([C:26]2[N:30]([CH3:31])[N:29]=[CH:28][N:27]=2)[S:25][C:21]=1[C:13]1[N:8]2[N:9]=[C:10]([CH3:12])[CH:11]=[C:6]([CH:3]([CH2:4][CH3:5])[CH2:1][CH3:2])[C:7]2=[N:15][C:14]=1[C:16]([F:18])([F:19])[F:17]

Participants

Conditions

Temperature: 125 °C

Procedure

In a dry 25 mL round bottom flask, 8-(1-ethyl-propyl)-6-methyl-2-trifluoromethyl-imidazo[1,2-b]pyridazine (182 mg, 0.671 mmol), 5-(5-bromo-4-chloro-thiophen-2-yl)-1-methyl-1H-[1,2,4]triazole (225 mg, 0.805 mmol), KOAc (330.2 mg, 3.36 mmol), and TBAB (217 mg, 0.671 mmol) are dissolved in NMP (3 mL). The mixture is degassed with bubbling nitrogen for 20 minutes. Then, Pd(OAc)2 (8 mg, 0.034 mmol) and TDBPP (20.4 g, 0.34 moles) are added. The reaction mixture is heated to 125° C. for 3 hours to give the title compound (125 mg, 0.267 mmol, 40%). 1H-NMR (CDCl3), δ 0.88 (t, J=7.2 Hz, 6H), 1.87 (m, 4H), 2.537 (s, 3H), 3.32 (m, 1H), 4.16 (s, 3H), 6.86 (s, 1H), 7.51 (s, 1H), 7.91 (s, 1H) ppm. ES-MS (m/z): calcd for C20H20ClF3N6S (M+H)+: 468.93; found: 469.2.

Workup

customThe mixture is degassed with bubbling nitrogen for 20 minutes

Sources & evidence

ORD record: ord-72dd38f9acf540bbb20468a5d9523ccc
Source dataset: uspto-grants-2009_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07612067B2

Reaction notes

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