5-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carboxylic acid [2-(4-methyl-piperazin-1-yl)-3-nitro-6-(2-trifluoromethyl-phenyl)-pyridin-4-yl]-amide → HCID 178480780, compound

HRID 1191247Notes

Reaction equation

HRID 1191247 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[C:13]([N+:14]([O-])=O)=[C:12]([NH:17][C:18]([C:20]3[N:21]([CH3:30])[N:22]=[C:23]([C:26]([CH3:29])([CH3:28])[CH3:27])[C:24]=3[Cl:25])=O)[CH:11]=[C:10]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=3[C:37]([F:40])([F:39])[F:38])[N:9]=2)[CH2:4][CH2:3]1>CC(O)=O.[Fe]>[C:26]([C:23]1[C:24]([Cl:25])=[C:20]([C:18]2[NH:14][C:13]3[C:8]([N:5]4[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH2:6]4)=[N:9][C:10]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=4[C:37]([F:39])([F:40])[F:38])=[CH:11][C:12]=3[N:17]=2)[N:21]([CH3:30])[N:22]=1)([CH3:28])([CH3:27])[CH3:29]

Participants

4

Reactant 1

HCID 674111645-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carboxylic acid [2-(4-methyl-piperazin-1-yl)-3-nitro-6-(2-trifluoromethyl-phenyl)-pyridin-4-yl]-amide

Product 1

HCID 178480780HCID 178480780, compound

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 176Acetic AcidSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 5-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carboxylic acid [2-(4-methyl-piperazin-1-yl)-3-nitro-6-(2-trifluoromethyl-phenyl)-pyridin-4-yl]-amide (300 mg, 0.517 mmol, prepared as described in the previous step) in AcOH (10 mL) was treated with iron powder (86.7 mg, 1.55 mmol) and heated to 100° C. for 5 h. The mixture was concentrated in vacuo, treated with saturated aqueous NaHCO3 (25 mL), and extracted three times with EtOAc (30 mL). The combined extracts were dried over MgSO4 and concentrated in vacuo. The residue was purified on a 12-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 3:17 v/v over 40 min) to yield 2-(5-tert-butyl-4-chloro-2-methyl-2H-pyrazol-3-yl)-4-(4-methyl-piperazin-1-yl)-6-(2-trifluoromethyl-phenyl)-3H-imidazo[4,5-c]pyridine as a tan solid. 1H-NMR (400 MHz, CDCl3) δ: 9.99 (s, 1H), 7.76 (d, J=7.6 Hz, 1H), 7.56-7.61 (m, 2H), 7.45-7.52 (m, 1H), 6.95 (s, 1H), 4.30 (s, 7H), 2.59 (t, J=4.9 Hz, 4H), 2.36 (s, 3H), 1.45 (s, 9H). Mass Spectrum (LCMS, APCI pos.): Calculated for C26H29ClF3N7: 532.2 (M+H); Measured: 532.2.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. additiontreated with saturated aqueous NaHCO3 (25 mL)
  3. extractionextracted three times with EtOAc (30 mL)
  4. dry with materialThe combined extracts were dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified on a 12-g SEPRA Si 50 SPE column (Isco system

Sources & evidence

ORD record
ord-59159875e5be404da42db26ff3817c3e
Source dataset
uspto-grants-2014_03
Patent number
US08680098B2

Reaction notes

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