1-Methylpiperazine → HCID 73330941, compound

HRID 1475192Notes

Reaction equation

HRID 1475192 reaction equation
Cl[C:2]1[CH:7]=[C:6]([CH2:8][N:9]2[C:13]([CH3:14])=[N:12][C:11]([C:15]3[O:16][C:17]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)=[CH:18][CH:19]=3)=[N:10]2)[CH:5]=[CH:4][N:3]=1.Cl[C:27]1[CH:32]=[C:31]([CH2:33][N:34]2[C:38]([C:39]3[O:40][C:41]([C:44]4[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=4)=[CH:42][CH:43]=3)=[N:37][C:36]([CH3:50])=[N:35]2)[CH:30]=[CH:29][N:28]=1.[CH3:51][N:52]1[CH2:57][CH2:56][NH:55][CH2:54][CH2:53]1>CCN(C(C)C)C(C)C>[CH3:51][N:52]1[CH2:57][CH2:56][N:55]([C:2]2[CH:7]=[C:6]([CH2:8][N:9]3[C:13]([CH3:14])=[N:12][C:11]([C:15]4[O:16][C:17]([C:20]5[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=5)=[CH:18][CH:19]=4)=[N:10]3)[CH:5]=[CH:4][N:3]=2)[CH2:54][CH2:53]1.[CH3:51][N:52]1[CH2:57][CH2:56][N:55]([C:27]2[CH:32]=[C:31]([CH2:33][N:34]3[C:38]([C:39]4[O:40][C:41]([C:44]5[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=5)=[CH:42][CH:43]=4)=[N:37][C:36]([CH3:50])=[N:35]3)[CH:30]=[CH:29][N:28]=2)[CH2:54][CH2:53]1

Participants

6

Reactant 3

HCID 531671-MethylpiperazineHCID 86711884HCID 86711884, compoundHCID 86711885HCID 86711885, compound

Product 2

HCID 73330941HCID 73330941, compoundYield 53%HCID 86711883HCID 86711883, compoundYield 34%

Reagents, catalysts & solvents 1

HCID 81531DiisopropylethylamineSolvent

Procedure

A mixture of 2-chloro-4-((5-methyl-3-(5-phenylfuran-2-yl)-1H-1,2,4-triazol-1-yl) methyl)pyridine and 2-chloro-4-((3-methyl-5-(5-phenylfuran-2-yl)-1H-1,2,4-triazol-1-yl)methyl)pyridine (100 mg, 0.3 mmol) was treated with 1-methylpiperazine (280 mg, 3 mmol) in DIEA (10 ml), and refluxed overnight. The mixture was cooled, concentrated, treated with H2O (30 mL) and extracted with EtOAc (3×30 mL). The combined organic layers were washed with H2O (1×10 mL) and brine (1×10 mL), dried over Na2SO4, filtered, and concentrated to afford the crude product, which was purified by prep-HPLC (Mobile phase: A=0.1% NH4OH/H2O, B=MeCN; Gradient: B=60%-95% in 18 min; Column: XBridge (C18, 5 um, 30 mm×150 mm) to give 1-methyl-4-(4-((5-methyl-3-(5-phenylfuran-2-yl)-1H-1,2,4-triazol-1-yl)methyl)pyridin-2-yl)piperazine as a yellow solid (66 mg, 53%) and 1-methyl-4-(4-((3-methyl-5-(5-phenylfuran-2-yl)-1H-1,2,4-triazol-1-yl)methyl)pyridin-2-yl)piperazine as a yellow solid (42 mg, 34%). For 1-methyl-4-(4-((5-methyl-3-(5-phenylfuran-2-yl)-1H-1,2,4-triazol-1-yl)methyl) pyridin-2-yl)piperazine: MS (ES+) C24H26N6O requires: 414. found: 415 [M+H]+. 1H NMR (500 MHz, CDCl3) δ 8.14 (d, J=5.1 Hz, 1H), 7.89-7.72 (m, 2H), 7.39 (t, J=7.8 Hz, 2H), 7.28 (td, J=7.4, 1.3 Hz, 1H), 7.04 (d, J=3.5 Hz, 1H), 6.76 (d, J=3.5 Hz, 1H), 6.44-6.26 (m, 2H), 5.26 (s, 2H), 3.53 (t, J=5.0 Hz, 4H), 2.48 (t, J=5.1 Hz, 4H), 2.44 (s, 3H), 2.32 (s, 3H).

Workup

  1. temperaturerefluxed overnight
  2. temperatureThe mixture was cooled
  3. concentrationconcentrated
  4. additiontreated with H2O (30 mL)
  5. extractionextracted with EtOAc (3×30 mL)
  6. washThe combined organic layers were washed with H2O (1×10 mL) and brine (1×10 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto afford the crude product, which
  11. customwas purified by prep-HPLC (Mobile phase

Sources & evidence

ORD record
ord-3fad15ed94e4447d989f7e1a7c1a8bec
Source dataset
uspto-grants-2015_04
Patent number
US09018380B2

Reaction notes

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