5-tert-butyl-2-methyl-2H-pyrazole-3-carboxylic acid (5-tert-butyl-2-methyl-2H-pyrazole-3-carbonyl)-[3-nitro-6-(2-trifluoromethyl-phenyl)-pyridin-2-yl]-amide → 2-(5-tert-butyl-2-methyl-2H-pyrazol-3-yl)-5-(2-trifluoromethyl-phenyl)-1H-imidazo[4,5-b]pyridine

HRID 570260Notes

Reaction equation

HRID 570260 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]([C:11]([N:13]([C:26]2[C:31]([N+:32]([O-])=O)=[CH:30][CH:29]=[C:28]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=3[C:41]([F:44])([F:43])[F:42])[N:27]=2)C(C2N(C)N=C(C(C)(C)C)C=2)=O)=O)[N:8]([CH3:10])[N:9]=1)([CH3:4])([CH3:3])[CH3:2]>C(O)(=O)C.[Fe]>[C:1]([C:5]1[CH:6]=[C:7]([C:11]2[NH:32][C:31]3[C:26]([N:13]=2)=[N:27][C:28]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=2[C:41]([F:43])([F:42])[F:44])=[CH:29][CH:30]=3)[N:8]([CH3:10])[N:9]=1)([CH3:3])([CH3:4])[CH3:2]

Participants

4

Reactant 1

HCID 674108155-tert-butyl-2-methyl-2H-pyrazole-3-carboxylic acid (5-tert-butyl-2-methyl-2H-pyrazole-3-carbonyl)-[3-nitro-6-(2-trifluoromethyl-phenyl)-pyridin-2-yl]-amide

Product 1

HCID 1360731632-(5-tert-butyl-2-methyl-2H-pyrazol-3-yl)-5-(2-trifluoromethyl-phenyl)-1H-imidazo[4,5-b]pyridine

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 176Acetic AcidSolvent

Conditions

Temperature
90 °C

Procedure

A solution of 5-tert-butyl-2-methyl-2H-pyrazole-3-carboxylic acid (5-tert-butyl-2-methyl-2H-pyrazole-3-carbonyl)-[3-nitro-6-(2-trifluoromethyl-phenyl)-pyridin-2-yl]-amide (339 mg, 0.554 mmol, prepared as described in the previous step) was taken up in acetic acid (10 mL), treated with iron powder (124 mg, 2.22 mmol), and heated to 90° C. for 15 h. The resulting mixture was concentrated to a volume of 3 mL, treated with saturated aqueous NaHCO3 (75 mL) and extracted twice with EtOAc (75 mL, 40 mL). The combined extracts were dried over MgSO4 and concentrated in vacuo. The residue was purified on a 24-g SEPRA Si 50 SPE column (Isco system: Flow rate=20 mL/min; Eluent=EtOAc/hexanes, 1:19 v/v for 5 min, then 1:19 to 1:4 v/v over 40 min) to yield 2-(5-tert-butyl-2-methyl-2H-pyrazol-3-yl)-5-(2-trifluoromethyl-phenyl)-1H-imidazo[4,5-b]pyridine as a white solid. 1H-NMR (400 MHz, CDCl3) δ: 8.13 (d, J=8.3 Hz, 1H), 7.81 (d, J=8.1 Hz, 1H), 7.61-7.68 (m, 1H), 7.52-7.59 (m, 2H), 7.40 (d, J=8.1 Hz, 1H), 6.56 (s, 1H), 4.37 (s, 3H), 1.37 (s, 9H). Mass Spectrum (LCMS, APCI pos.): Calculated for C21H20F3N5: 400.2 (M+H); Measured: 400.2.

Workup

  1. concentrationThe resulting mixture was concentrated to a volume of 3 mL
  2. additiontreated with saturated aqueous NaHCO3 (75 mL)
  3. extractionextracted twice with EtOAc (75 mL, 40 mL)
  4. dry with materialThe combined extracts were dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified on a 24-g SEPRA Si 50 SPE column (Isco system

Sources & evidence

ORD record
ord-378435ae8b134c809577d1554af52fa1
Source dataset
uspto-grants-2015_05
Patent number
US09023846B2

Reaction notes

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