1-Methylpiperazine → HCID 73330789, compound

HRID 517569Notes

Reaction equation

HRID 517569 reaction equation
Cl[C:2]1[CH:7]=[C:6]([CH2:8][C:9]2[N:10]([CH3:30])[CH:11]=[C:12]([C:14]3[O:18][N:17]=[C:16]([C:19]4[CH:24]=[CH:23][C:22]([O:25][C:26]([F:29])([F:28])[F:27])=[CH:21][CH:20]=4)[N:15]=3)[N:13]=2)[CH:5]=[CH:4][N:3]=1.[CH3:31][N:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1>CCN(C(C)C)C(C)C>[CH3:30][N:10]1[CH:11]=[C:12]([C:14]2[O:18][N:17]=[C:16]([C:19]3[CH:24]=[CH:23][C:22]([O:25][C:26]([F:29])([F:28])[F:27])=[CH:21][CH:20]=3)[N:15]=2)[N:13]=[C:9]1[CH2:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([N:35]2[CH2:36][CH2:37][N:32]([CH3:31])[CH2:33][CH2:34]2)[CH:7]=1

Participants

4

Reactant 2

HCID 531671-MethylpiperazineHCID 86711509HCID 86711509, compound

Product 1

HCID 73330789HCID 73330789, compoundYield 12.8%

Reagents, catalysts & solvents 1

HCID 81531DiisopropylethylamineSolvent

Procedure

A solution of 5-(2-((2-chloropyridin-4-yl)methyl)-1-methyl-1H-imidazol-4-yl)-3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazole (60 mg, 0.138 mmol) and 1-methylpiperazine (2 mL) in DIPEA (2 mL) was stirred at 150° C. for 5 h. After cooled to RT, the mixture was quenched by water (5 mL), and extracted with EtOAc (2×10 mL). The combined organic phases were washed with water (5 mL) and brine (5 mL), dried (Na2SO4), filtered, and concentrated to afford the crude product, which was purified with prep-HPLC (Mobile phase:A=0.01% formic acid/water, B=acetonitrile; Gradient: B=36%-95% in 18 min; Column: XBridge C18, 5 um, 30 mm×150 mm) to give 5-(1-methyl-2-((2-(4-methylpiperazin-1-yl)pyridin-4-yl)methyl)-1H-imidazol-4-yl)-3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazole as a white solid (8.8 mg, 12.8%). MS (ES+) C24H24F3N7O2 requires: 499, found: 500 [M+H]+; 1H-NMR (500 MHz, CDCl3) δ ppm 8.20 (d, J=7.5 Hz, 2H), 8.14 (d, J=5.0 Hz, 1H), 7.63 (t, 1H), 7.32 (d, J=4 Hz, 2H), 6.58 (d, J=5 Hz, 1H), 6.47 (s, 1H), 4.53 (s, 2H), 3.79-3.74 (m, 2H), 3.63-3.58 (m, 2H), 3.56 (s, 3H), 3.29-3.25 (m, 2H), 2.92-2.87 (m, 2H), 2.79 (s, 3H).

Workup

  1. customthe mixture was quenched by water (5 mL)
  2. extractionextracted with EtOAc (2×10 mL)
  3. washThe combined organic phases were washed with water (5 mL) and brine (5 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto afford the crude product, which
  8. customwas purified with prep-HPLC (Mobile phase

Sources & evidence

ORD record
ord-df733efa088745b09619adc300339190
Source dataset
uspto-grants-2015_08
Patent number
US09115120B2

Reaction notes

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