HCID 67411418, compound → HCID 136073160, compound

HRID 1481578Notes

Reaction equation

HRID 1481578 reaction equation
[N+:1]([C:4]1[C:5]([NH:20][C:21]([C:23]2[O:27][N:26]=[C:25]([C:28]([CH3:31])([CH3:30])[CH3:29])[CH:24]=2)=O)=[N:6][C:7]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]([F:19])([F:18])[F:17])=[CH:8][CH:9]=1)([O-])=O>C(O)(=O)C.[Fe]>[C:28]([C:25]1[CH:24]=[C:23]([C:21]2[NH:1][C:4]3[C:5]([N:20]=2)=[N:6][C:7]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]([F:19])([F:18])[F:17])=[CH:8][CH:9]=3)[O:27][N:26]=1)([CH3:31])([CH3:30])[CH3:29]

Participants

4

Reactant 1

HCID 67411418HCID 67411418, compound

Product 1

HCID 136073160HCID 136073160, compound

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 176Acetic AcidSolvent2×

Conditions

Temperature
100 °C

Procedure

A solution of 3-tert-butyl-isoxazole-5-carboxylic acid [3-nitro-6-(2-trifluoromethyl-phenyl)-pyridin-2-yl]-amide (78.0 mg, 0.180 mmol, prepared as described in the previous step) in acetic acid (5 mL) was treated with iron powder (50.1 mg, 0.898 mmol) and heated to 100° C. for 2 h. The volume of acetic acid was reduced to 2 mL by concentrating in vacuo, and saturated aqueous NaHCO3 (50 mL) was added. The resulting mixture was extracted twice with EtOAc (60 mL). The combined extracts were dried over MgSO4 and concentrated in vacuo. The residue was purified on a 4-g SEPRA Si 50 SPE column (Isco system: Flow rate=10 mL/min; Eluent=EtOAc/hexanes, 1:99 v/v for 5 min, then 1:99 to 1:9 v/v over 40 min) to yield 2-(3-tert-butyl-isoxazol-5-yl)-5-(2-trifluoromethyl-phenyl)-1H-imidazo[4,5-b]pyridine as a white solid. 1H-NMR (400 MHz, CDCl3) δ: 10.06 (br. s., 1H), 8.16 (d, J=8.3 Hz, 1H), 7.81 (d, J=8.1 Hz, 1H), 7.64 (d, J=7.6 Hz, 1H), 7.52-7.60 (m, 2H), 7.46 (d, J=8.3 Hz, 1H), 7.07 (s, 1H), 1.42 (s, 9H). Mass Spectrum (LCMS, APCI pos.): Calculated for C20H17F3N4O: 387.1 (M+H). Measured: 387.1.

Workup

  1. concentrationby concentrating in vacuo, and saturated aqueous NaHCO3 (50 mL)
  2. additionwas added
  3. extractionThe resulting mixture was extracted twice with EtOAc (60 mL)
  4. dry with materialThe combined extracts were dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified on a 4-g SEPRA Si 50 SPE column (Isco system

Sources & evidence

ORD record
ord-e94ba42793204777bab785b3ff06db27
Source dataset
uspto-grants-2016_08
Patent number
US09409915B2

Reaction notes

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