Tetrahydrofuran → HCID 57933033, compound

HRID 1432604Notes

Reaction equation

HRID 1432604 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-].[CH2:25]([Zn+])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.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]>[CH2:25]([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)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

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 178419772HCID 178419772, compound

Product 1

HCID 57933033HCID 57933033, compoundYield 20%

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 (0.30 g, 0.765 mmol) and PdCl2(dppf) (0.028 g, 0.038 mmol) and 0.5 M solution of benzylzinc bromide in THF (4.6 mL, 2.29 mmol) are reacted. The residue is purified by ISCO column chromatography (15%-20% EtOAc/hexane gradient) and is chromatographed (50×250 C18 Symmetry column, 40-65% water: 0.1% TFA/ACN: 0.1% TFA gradient) furnish the title compound (0.062 g, 0.15 mmol, 20%). 1H NMR (CDCl3), δ 0.88 (t, J=7.5 Hz, 6H), 1.73-1.92 (m, 4H), 2.06 (s, 3H), 2.45 (s, 3H), 2.51 (s, 3H), 3.29-3.39 (m, 1H), 4.16 (s, 2H), 6.65 (s, 1H), 6.68 (s, 1H), 7.22-7.29 (m, 1H), 7.31-7.36 (m, 4H). LC/MS (m/z): calcd. for C25H29N3S (M+H)+: 404.3; found: 404.2.

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, 40-65% water: 0.1% TFA/ACN: 0.1% TFA gradient)

Sources & evidence

ORD record
ord-d7e3b69f032d4b91b1a86a038276d1f3
Source dataset
uspto-grants-2009_11
Patent number
US07612067B2

Reaction notes

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