Tetrahydrofuran → HCID 57932962, compound

HRID 1432603Notes

Reaction equation

HRID 1432603 reaction equation
Br[C:2]1[S:6][C:5]([C:7]2[N:11]3[N:12]=[C:13]([CH3:21])[CH:14]=[C:15]([CH:16]([CH2:19][CH3:20])[CH2:17][CH3:18])[C:10]3=[N:9][C:8]=2[CH3:22])=[C:4]([CH3:23])[CH:3]=1.[Br-].[F:25][C:26]1[CH:27]=[C:28]([Zn+])[CH:29]=[CH:30][C:31]=1[F:32].C1COCC1>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]>[F:25][C:26]1[CH:27]=[C:28]([C:2]2[S:6][C:5]([C:7]3[N:11]4[N:12]=[C:13]([CH3:21])[CH:14]=[C:15]([CH:16]([CH2:19][CH3:20])[CH2:17][CH3:18])[C:10]4=[N:9][C:8]=3[CH3:22])=[C:4]([CH3:23])[CH:3]=2)[CH:29]=[CH:30][C:31]=1[F:32]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 579329433-(5-Bromo-3-methyl-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazineHCID 178505907HCID 178505907, compound

Product 1

HCID 57932962HCID 57932962, compoundYield 33%

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Procedure

Using a procedure similar to Example 32, 3-(5-bromo-3-methyl-thiophen-2-yl)-8-(1-ethyl-propyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (0.50 g, 1.27 mmol) and PdCl2(dppf) (0.047 g, 0.064 mmol) and 0.5 M solution of 3,4-difluorophenylzinc bromide in THF (5.1 mL, 2.55 mmol) are reacted. The residue is purified by ISCO column chromatography (15%-20% EtOAc/hexane gradient) and is chromatographed (50×250 C18 Symmetry column, 30-80% water: 0.1% TPA/ACN: 0.1% TFA gradient) furnish the title compound (0.18 g, 0.42 mmol, 33%). 1H NMR (CDCl3), δ 0.90 (t, J=7.5 Hz, 6H), 1.76-1.94 (m, 4H), 2.16 (s, 3H), 2.50 (s, 3H), 2.54 (s, 3H), 3.31-3.40 (m, 1H), 6.69 (s, 1H), 7.13-7.21 (m, 1H), 7.18 (s, 1H), 7.31-7.36 (m, 1H), 7.39-7.46 (m, 1H). LC/MS (m/z): calcd. for C24H25F2N3S (M+H)+: 426.3; found: 426.2.

Workup

  1. customare reacted
  2. customThe residue is purified by ISCO column chromatography (15%-20% EtOAc/hexane gradient)
  3. customis chromatographed (50×250 C18 Symmetry column, 30-80% water: 0.1% TPA/ACN: 0.1% TFA gradient)

Sources & evidence

ORD record
ord-f36918487f6c4a5e90fd9bb61ecaec63
Source dataset
uspto-grants-2009_11
Patent number
US07612067B2

Reaction notes

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