1-(Dimethylamino)pyrrole → (2-{4-Chloro-5-[8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazin-3-yl]-thiophen-2-yl}-pyrrol-1-yl)-dimethyl-amine

HRID 1432702Notes

Reaction equation

HRID 1432702 reaction equation
[CH3:1][N:2]([CH3:8])[N:3]1[CH:7]=[CH:6][CH:5]=[CH:4]1.[Li]CCCC.Br[C:15]1[S:19][C:18]([C:20]2[N:24]3[N:25]=[C:26]([CH3:34])[CH:27]=[C:28]([CH:29]([CH2:32][CH3:33])[CH2:30][CH3:31])[C:23]3=[N:22][C:21]=2[CH3:35])=[C:17]([Cl:36])[CH:16]=1>[Cl-].[Cl-].[Zn+2].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].C1COCC1>[Cl:36][C:17]1[CH:16]=[C:15]([C:4]2[N:3]([N:2]([CH3:8])[CH3:1])[CH:7]=[CH:6][CH:5]=2)[S:19][C:18]=1[C:20]1[N:24]2[N:25]=[C:26]([CH3:34])[CH:27]=[C:28]([CH:29]([CH2:30][CH3:31])[CH2:32][CH3:33])[C:23]2=[N:22][C:21]=1[CH3:35]

Participants

7

Reactant 3

HCID 5735271-(Dimethylamino)pyrroleHCID 579329223-(5-Bromo-3-chloro-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazineHCID 178418339Butyllithium

Product 1

HCID 57932942(2-{4-Chloro-5-[8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazin-3-yl]-thiophen-2-yl}-pyrrol-1-yl)-dimethyl-amineYield 46.3%

Reagents, catalysts & solvents 3

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

Procedure

Using a procedure analogous to Example 27, 1-(dimethylamino)-pyrrole (0.20 mL, 1.65 mmol), THF (4 mL), 1.6 M n-BuLi (1.10 mL, 1.73 mmol), 0.5 M ZnCl2 (3.46 mL, 1.73 mmol), 3-(5-bromo-3-chloro-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (0.34 g, 0.82 mmol) and PdCl2(dppf) (0.030 g, 0.041 mmol), furnish the title compound (0.17 g, 0.38 mmol, 46%). 1H NMR (CDCl3) δ 0.87 (t, J=7.5 Hz, 6H), 1.74-1.92 (m, 4H), 2.52 (s, 6H), 2.84 (s, 6H), 3.28-3.39 (m, 1H), 6.21 (dd, J=4.1, 3.2 Hz, 1H), 6.38 (dd, J=4.1, 1.8 Hz, 1H), 6.68 (s, 1H), 7.02 (dd, J=3.2, 1.8 Hz, 1H), 7.29 (s, 1H). LC/MS (m/z): calcd. for C23H28ClN5S (M+H)+: 442.2; found: 442.3.

Sources & evidence

ORD record
ord-812ad80178584d6b91454d09df863c02
Source dataset
uspto-grants-2009_11
Patent number
US07612067B2

Reaction notes

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