Hydrazine → 2-chloro-N'-(5-(6-(4-fluorophenyl)imidazo[2,1-b]oxazol-5-yl)pyridin-2-yl)benzohydrazide

HRID 1711777Notes

Reaction equation

HRID 1711777 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[N:14]([C:15]=2[C:16]2[CH:17]=[N:18][C:19]([NH:22][NH2:23])=[CH:20][CH:21]=2)[CH:13]=[CH:12][O:11]3)=[CH:4][CH:3]=1.FC1C=CC(C2N=C3N(C=2)C=CO3)=CC=1.C1C(=O)N(I)C(=O)C1.FC1N=CC(B(O)O)=CC=1.NN.[Cl:59][C:60]1[CH:68]=[CH:67][CH:66]=[CH:65][C:61]=1[C:62](Cl)=[O:63]>C1COCC1.C(Cl)Cl>[Cl:59][C:60]1[CH:68]=[CH:67][CH:66]=[CH:65][C:61]=1[C:62]([NH:23][NH:22][C:19]1[CH:20]=[CH:21][C:16]([C:15]2[N:14]3[C:10]([O:11][CH:12]=[CH:13]3)=[N:9][C:8]=2[C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)=[CH:17][N:18]=1)=[O:63]

Participants

9

Reactant 6

HCID 9321HydrazineHCID 691102-Chlorobenzoyl chlorideHCID 120273N-IodosuccinimideHCID 2783397(6-Fluoropyridin-3-yl)boronic acidHCID 574336106-(4-Fluorophenyl)-imidazo[2,1-b]oxazoleHCID 594577926-(4-Fluorophenyl)-5-(6-hydrazinylpyridin-3-yl)imidazo[2,1-b]oxazole

Product 1

HCID 594578682-chloro-N'-(5-(6-(4-fluorophenyl)imidazo[2,1-b]oxazol-5-yl)pyridin-2-yl)benzohydrazideYield 89%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A 100 mL round-bottom flask charged with 6-(4-fluorophenyl)-5-(6-hydrazinylpyridin-3-yl)imidazo[2,1-b]oxazole (0.35 g, 1.1 mmol; prepared from A using 6-(4-fluorophenyl)-imidazo[2,1-b]oxazole [WO2004110990A2, Example 1, Steps 1-3], and NIS, C using 6-fluoropyridin-3-ylboronic acid [Asymchem], and D using 1M hydrazine in THF) in THF (10 mL) and DCM (10 mL) was treated with TEA (0.17 mL, 1.2 mmol) and 2-chlorobenzoyl chloride (0.14 mL, 1.1 mmol). The reaction mixture was stirred at ambient temperature for about 30 min. The reaction mixture was then washed with water, dried over MgSO4, filtered, and evaporated under reduced pressure to give 2-chloro-N′-(5-(6-(4-fluorophenyl)imidazo[2,1-b]oxazol-5-yl)pyridin-2-yl)benzohydrazide (0.50 g, 1.1 mmol, 89%). The crude material was dissolved in 1,4-dioxane (10 mL) and treated with thionyl chloride (0.2 mL, 2.8 mmol). After about 30 min at about 100° C., the reaction mixture was cooled to about 0° C. and the precipitate was collected by filtration and washed with DCM (5 mL). The solid was dissolved in EtOAc/MeOH and washed twice with water. The organic layer was dried over MgSO4, filtered, and concentrated under reduced pressure. The mixture was purified by column chromatography using EtOAc then EtOAc/MeOH (98:2) as eluent and dried in a vacuum oven at about 50° C. to give the title compound as a tan solid (0.13 g, 27%): LC/MS (Table 1, Method a) Rt, =2.38 min; MS m/z: 430.1 (M+H)+.

Workup

  1. washThe reaction mixture was then washed with water
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-42d2add4386f4cf0b01a0ea9e0181e51
Source dataset
uspto-grants-2010_09
Patent number
US07790741B2

Reaction notes

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