3-Tert-butyl-isoxazole-5-carboxylic acid [3-nitro-4-trifluoromethyl-6-(2-trifluoromethyl-phenyl)-pyridin-2-yl]-amide → 2-(3-tert-butyl-isoxazol-5-yl)-7-trifluoromethyl-5-(2-trifluoromethyl-phenyl)-1H-imidazo[4,5-b]pyridine

HRID 570225Notes

Reaction equation

HRID 570225 reaction equation
[N+:1]([C:4]1[C:5]([NH:24][C:25]([C:27]2[O:31][N:30]=[C:29]([C:32]([CH3:35])([CH3:34])[CH3:33])[CH:28]=2)=O)=[N:6][C:7]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[C:20]([F:23])([F:22])[F:21])=[CH:8][C:9]=1[C:10]([F:13])([F:12])[F:11])([O-])=O>CC(O)=O.[Fe]>[C:32]([C:29]1[CH:28]=[C:27]([C:25]2[NH:1][C:4]3[C:5]([N:24]=2)=[N:6][C:7]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[C:20]([F:21])([F:23])[F:22])=[CH:8][C:9]=3[C:10]([F:13])([F:12])[F:11])[O:31][N:30]=1)([CH3:33])([CH3:35])[CH3:34]

Participants

4

Reactant 1

HCID 866574113-Tert-butyl-isoxazole-5-carboxylic acid [3-nitro-4-trifluoromethyl-6-(2-trifluoromethyl-phenyl)-pyridin-2-yl]-amide

Product 1

HCID 1360731612-(3-tert-butyl-isoxazol-5-yl)-7-trifluoromethyl-5-(2-trifluoromethyl-phenyl)-1H-imidazo[4,5-b]pyridine

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 176Acetic AcidSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 3-tert-butyl-isoxazole-5-carboxylic acid [3-nitro-4-trifluoromethyl-6-(2-trifluoromethyl-phenyl)-pyridin-2-yl]-amide (14.6 mg, 0.029 mmol, prepared as described in STEP E above) in AcOH (3 mL) was treated with iron powder (8.12 mg, 0.145 mmol), and the resulting mixture was stirred at 100° C. for 2 h and concentrated in vacuo. The residue was taken up in saturated aqueous NaHCO3 (30 mL) and extracted twice with EtOAc (25 mL). The combined organic extracts were dried over MgSO4 and concentrated in vacuo. The residue was purified on a 4-g SEPRA Si 50 SPE column (Flow rate=10 mL/min; Eluent=EtOAc-hexanes, 1:99 for 10 min, then 1:99 to 1:4 over 40 min) to yield 2-(3-tert-butyl-isoxazol-5-yl)-7-trifluoromethyl-5-(2-trifluoromethyl-phenyl)-1H-imidazo[4,5-b]pyridine as a white solid. 1H-NMR (400 MHz, CD3OD) δ: 7.77 (d, J=7.6 Hz, 1H), 7.63-7.69 (m, 1H), 7.58-7.62 (m, 2H), 7.52-7.58 (m, 1H), 7.26 (s, 1H), 1.33 (s, 9H). Mass Spectrum (LCMS, APCI pos.): Calculated for C21H16N4OF6: 455.1 (M+H); Measured: 455.1.

Workup

  1. concentrationconcentrated in vacuo
  2. extractionextracted twice with EtOAc (25 mL)
  3. dry with materialThe combined organic extracts were dried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified on a 4-g SEPRA Si 50 SPE column (Flow rate=10 mL/min
  6. waitEluent=EtOAc-hexanes, 1:99 for 10 min

Sources & evidence

ORD record
ord-b2a962fd69724c269701867d403667ac
Source dataset
uspto-grants-2015_05
Patent number
US09023846B2

Reaction notes

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