1-Methylpiperazine → HCID 90403793, compound

HRID 1049335Notes

Reaction equation

HRID 1049335 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[C:11]([O:13][C:14]3[CH:15]=[CH:16][C:17]([NH2:20])=[N:18][CH:19]=3)[CH:10]=[CH:9][N:8]=2)[CH:4]=[N:3]1.Cl[CH2:22][C:23]([N:25]=[C:26]=[O:27])=[O:24].[CH3:28][N:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1>C1COCC1.CCOC(C)=O>[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[C:11]([O:13][C:14]3[CH:15]=[CH:16][C:17]([NH:20][C:26]([NH:25][C:23](=[O:24])[CH2:22][N:32]4[CH2:33][CH2:34][N:29]([CH3:28])[CH2:30][CH2:31]4)=[O:27])=[N:18][CH:19]=3)[CH:10]=[CH:9][N:8]=2)[CH:4]=[N:3]1

Participants

6

Reactant 3

HCID 531671-MethylpiperazineHCID 78209Chloroacetyl isocyanateHCID 593227775-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)pyridin-2-amine

Product 1

HCID 90403793HCID 90403793, compoundYield 30.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of Example A2 (0.15 g, 0.561 mmol) in THF (3 mL) was treated with TEA (0.114 g, 1.122 mmol) and 2-chloroacetyl isocyanate (0.107 g, 0.898 mmol), stirred at RT for 2 h, treated with N-methylpiperazine (0.112 g, 1.122 mmol) and stirred at RT for 4 h. The mixture was diluted with EtOAc, stirred for several minutes, the solids removed via filtration and the filtrate concentrated to dryness and purified via silica gel chromatography (NH4OH/MeOH/DCM). The material was suspended in 2:1 EtOAc/DCM and the solid was removed via filtration and discarded. The filtrate was concentrated to dryness and treated with 3:2 EtOAc/Hex. The mixture was briefly sonicated. The solid was collected via filtration, dissolved in MeCN/H2O, frozen and lyophilized to afford N-((5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)-2-(4-methylpiperazin-1-yl)acetamide (76 mg, 30%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 10.88 (s, 1H), 10.48 (br s, 1H), 8.37 (d, J=5.7 Hz, 1H), 8.27-8.24 (m, 2H), 8.07-8.00 (m, 1H), 7.96 (d, J=0.7 Hz, 1H), 7.74 (dd, J=9.0, 2.9 Hz, 1H), 7.23 (d, J=2.4 Hz, 1H), 6.70 (dd, J=5.7, 2.4 Hz, 1H), 3.84 (s, 3H), 3.22 (s, 2H), 2.51 (m, 4H), 2.35 (m, 4H), 2.15 (s, 3H); MS (ESI) m/z: 451.2 (M+H+).

Workup

  1. stirringstirred at RT for 4 h
  2. stirringstirred for several minutes
  3. customthe solids removed via filtration
  4. concentrationthe filtrate concentrated to dryness
  5. custompurified via silica gel chromatography (NH4OH/MeOH/DCM)
  6. customthe solid was removed via filtration
  7. concentrationThe filtrate was concentrated to dryness
  8. additiontreated with 3:2 EtOAc/Hex
  9. customThe mixture was briefly sonicated
  10. filtrationThe solid was collected via filtration
  11. dissolutiondissolved in MeCN/H2O
  12. temperaturefrozen

Sources & evidence

ORD record
ord-a47f8dad48104066a2c1560e181c82af
Source dataset
uspto-grants-2016_07
Patent number
US09382228B2

Reaction notes

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